Endocrine Disruption

Front Cell Dev Biol. 2026 Mar 31;14:1797181. doi: 10.3389/fcell.2026.1797181. eCollection 2026.

ABSTRACT

Digestive tract tumors (DTT), particularly gastric cancer (GC) and colorectal cancer (CRC), remain among the leading causes of cancer-related morbidity and mortality worldwide. Accumulating epidemiological evidence indicates that patients with chronic kidney disease (CKD) exhibit a significantly increased risk of developing gastrointestinal malignancies and experience worse clinical outcomes. However, the biological mechanisms underlying this association have not been comprehensively synthesized. In this review, we integrate clinical and experimental evidence to delineate how CKD functions as a systemic pro-tumorigenic condition rather than a passive comorbidity. We highlight three interrelated mechanistic axes linking CKD to DTT: (i) persistent systemic inflammation and oxidative stress, (ii) metabolic and endocrine dysregulation driven by uremic toxin accumulation, vitamin D deficiency, and mineral imbalance, and (iii) immune perturbations associated with dialysis modalities and post-transplant immunosuppression. These processes converge to disrupt gastrointestinal barrier integrity, reshape the gut microbiota, impair antitumor immune surveillance, and promote malignant transformation and tumor progression. Importantly, we discuss how CKD-specific interventions, including dialysis strategies, kidney transplantation, dietary management, and modulation of gut microbiota, may further modify gastrointestinal cancer risk. Finally, we propose CKD-oriented preventive and screening strategies for GC and CRC, emphasizing the need for risk stratification based on renal function, proteinuria, and metabolic profiles. By framing CKD as an active driver of gastrointestinal carcinogenesis, this review provides a novel integrative framework that synthesizes interconnected mechanistic pathways and explicitly links them to CKD-specific clinical management strategies, a translational perspective that informs early detection, prevention, and integrated care of DTT in patients with CKD.

PMID:41988382 | PMC:PMC13076587 | DOI:10.3389/fcell.2026.1797181

Reprod Domest Anim. 2026 Apr;61(4):e70204. doi: 10.1111/rda.70204.

ABSTRACT

Linuron, chloridazon and metribuzin are herbicides thought to have potential endocrine disruption (ED) effects. This study investigated the effects of linuron, chloridazon and metribuzin on bovine granulosa cell viability and oestrogen (E2) and progesterone (P4) secretion in vitro. Cells were exposed to 10, 50 and 250 μM linuron; 10, 100 and 1000 μM chloridazon, and 25, 250 and 2500 μM metribuzin for 48 and 96 h. At both time points, linuron had no effect on cell viability, whereas chloridazon and metribuzin decreased viability at the highest doses. E2 and P4 release decreased at 96 h in all groups, with significant differences observed at the highest doses (250 μM linuron, 1000 μM chloridazon and 2500 μM metribuzin). The study demonstrated that chloridazon and metribuzin exerted cytotoxic effects at the highest concentrations and that all three herbicides disrupted E2 and P4 secretion in a time-by-dose dependent manner. The results of this study may serve to raise awareness of the endocrine-disrupting effects of herbicides and to promote the consideration of alternatives for use that do not harm animal and human health.

PMID:41987673 | DOI:10.1111/rda.70204

Small. 2026 Apr 16:e13075. doi: 10.1002/smll.202513075. Online ahead of print.

ABSTRACT

Bisphenol S (BPS), a widely used substitute for bisphenol A, is an environmental contaminant with endocrine-disrupting properties. However, the transgenerational impact of maternal BPS exposure during gestation on male offspring reproductive health and the underlying molecular mechanisms remains unknown. This study shows that gestational exposure of mice to environmentally relevant concentrations of BPS (3, 30, and 300 µg/kg) dose- and time-dependently impairs testicular development and sperm function in male offspring. Integrated transcriptomic, physiological, and molecular analyses revealed that maternal BPS exposure remodeled the testicular transcriptome and disrupted the immune-endocrine crosstalk within the testis. This disruption was characterized by the aberrant activation of immune and inflammatory pathways, including antigen presentation, concomitant suppression of steroidogenic and metabolic processes, and induction of the renin-angiotensin system. Deconvolution analysis identified loss of Leydig cells and increased Tcell infiltration, and quantitative realtime PCR validated the dysregulation of key hub genes such as Ren1, H2-D1, Naip6, Tlr1, H2-M3, Pycard, B2m, H2-Aa, Naip1, and Cd74. Notably, western blotting revealed that HLA-DPB1, a key component of the antigen presentation pathway, was significantly downregulated at the protein level in testicular tissues. Immunofluorescence co-localization with cell-specific markers defined the precise cellular localization in the testis. Collectively, these multilevel disruptions resulted in impaired seminiferous epithelial cyclicity, enhanced interstitial collagen deposition in the testes, and severe deficits in sperm motility. Our findings reveal a novel transgenerational mechanism underlying BPS-induced testicular injury and provide robust experimental evidence of the reproductive toxicity of environmentally relevant BPS in male offspring.

PMID:41988921 | DOI:10.1002/smll.202513075

J Endocr Soc. 2026 Mar 31;10(5):bvag076. doi: 10.1210/jendso/bvag076. eCollection 2026 May.

ABSTRACT

PURPOSE: Estimates of human exposure are a major component of chemical risk assessment. Studies of bisphenol A (BPA) have raised concern that exposure has been underestimated because the lack of standards for the measurement of the major BPA metabolites has necessitated the use of flawed analytical tools to indirectly estimate them. Because other endocrine-disrupting chemicals (EDCs) are measured using similar indirect methods, we evaluated the accuracy of indirect analysis for representatives from three different classes of non-persistent EDCs that undergo rapid phase II metabolism: bisphenols, parabens, and phthalates.

METHODS: A direct LC-MS/MS method that simultaneously measures bisphenol S (BPS), propyl paraben (PrP), and monobutyl phthalate (MBP), and their major metabolites in urine, was used to quantify these EDCs in sixty second-trimester human urine samples. The same samples were also analyzed with a widely used indirect method that requires enzymatic hydrolysis before estimating metabolite levels.

RESULTS: Marked discrepancies were evident when maternal urine samples were analyzed by both direct and indirect methods. Indirect analysis underestimated levels of all three EDCs and BPA, with the magnitude of underestimation varying by analyte.

CONCLUSION: The accuracy of widely used "indirect" analytical methods that estimate metabolite levels in human urine is neither predictable nor consistent. Greater precision and accuracy is attained using authentic standards for metabolites. Given the importance of biomonitoring data in estimating human EDC exposure, analytical accuracy is critical. Availability of standards for both the parent compound and its major metabolites should be required before a chemical enters the marketplace.

PMID:41982343 | PMC:PMC13071811 | DOI:10.1210/jendso/bvag076

RSC Adv. 2026 Apr 13;16(20):18374-18388. doi: 10.1039/d6ra01469k. eCollection 2026 Apr 1.

ABSTRACT

Bisphenol A (BPA) is a persistent endocrine-disrupting compound frequently detected in aquatic environments and inadequately removed by conventional wastewater treatment processes. In this work, a visible-light-active TiO₂-metalloporphyrin hybrid photocatalyst was developed via surface sensitization of TiO₂ with zinc tetrakis(4-carboxyphenyl)porphyrin (ZnTCPP) and evaluated for BPA degradation in aqueous media. The hybrid material was characterized by UV-Vis spectroscopy (UV-Vis), Fourier Transform Infrared (FT-IR) Spectroscopy, powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM), confirming successful porphyrin immobilization without altering the anatase crystal structure. Photocatalytic experiments under visible-light irradiation demonstrated efficient BPA removal, reaching up to 70% degradation within 180 min, while maintaining stable performance over three successive cycles. Kinetic analysis revealed that BPA degradation followed a power law kinetic model, with enhanced reaction rates under acidic conditions and optimized catalyst loading. Radical scavenging experiments indicated that superoxide and hydroxyl radicals were the dominant reactive species governing the oxidation process. High-resolution Orbitrap mass spectrometry enabled the identification of major transformation products and the elucidation of degradation pathways, which were dominated by aromatic hydroxylation and C-C bond cleavage reactions. In silico ECOSAR toxicity assessment showed a substantial reduction in acute and chronic aquatic toxicity for the main intermediates compared with the parent BPA molecule. Overall, the TiO₂-metalloporphyrin hybrid effectively extends photocatalytic activity into the visible region and enables efficient pollutant removal with reduced environmental risk, highlighting its potential for sustainable solar-driven water treatment applications.

PMID:41983111 | PMC:PMC13074201 | DOI:10.1039/d6ra01469k

Braz J Biol. 2026 Apr 10;86:e298520. doi: 10.1590/1519-6984.298520. eCollection 2026.

ABSTRACT

Endocrine disruption, infertility, anovulation, impaired cyclicity, and ovarian damage are complications of polycystic ovary syndrome (PCOS). Herein, we explore the potential role of Costus speciosus extract in letrozole-induced polycystic ovary syndrome in female rats. For PCOS induction, letrozole 1.0 mg/kg body weight was given orally for 90 days. Four groups of female rats were randomly assigned. Group 1, the control, was orally administered distilled water. Group 2 received 300 mg/kg Costus speciosus extract for 28 days. Group 3 is the PCOS model. Group 4 PCOS received 300 mg/kg Costus speciosus extract for 28 days. PCOS phenotypes were evaluated, including testosterone, luteinizing hormone, estradiol, and follicle-stimulating hormone levels. Body and ovarian weights, estrus cyclicity, follicular cysts, and ovarian histopathology were assessed. Compared to controls, letrozole induced a significant increase in body and ovarian weights. In addition, impaired cyclicity, increased testosterone, LH, and FSH levels, and decreased estradiol were observed. Moreover, ovarian damage was evident by many antral follicular arrests and multiple cystic follicles. Neuroendocrine disruption, reproductive deficiency, and ovarian histopathological alterations were alleviated after 28 days of Costus speciosus treatment. Restoring the estrus cyclicity, significant decreases in LH and testosterone levels with increased estradiol concentration were evident after Costus speciosus treatment. Recovery of arrested and cystic follicles was also obvious after Costus speciosus application. Consequently, we suggest that Costus speciosus could be an alleviating agent in PCOS phenotypes. However, Further research should be conducted to elucidate the underlying molecular mechanisms of Costus speciosus or its phytoconstituents per se in the circumstances of PCOS, confirming the present findings.

PMID:41983838 | DOI:10.1590/1519-6984.298520

Chem Res Toxicol. 2026 Apr 15. doi: 10.1021/acs.chemrestox.5c00375. Online ahead of print.

ABSTRACT

Human and environmental health are critically threatened by combined exposures to multiple chemical toxicants, including industrial chemicals, heavy metals, pesticides, endocrine-disrupting chemicals (EDCs), and per- and polyfluoroalkyl substances (PFAS). These substances interact biologically, producing additive, synergistic, or antagonistic effects that conventional single-substance risk assessments fail to predict. This leads to a systematic underestimation of health risks, particularly for vulnerable populations. Despite robust evidence on mixture toxicity, major regulatory frameworks such as the US Toxic Substances Control Act (TSCA) and the EU's REACH program continue to assess chemicals in isolation. This review synthesizes current science on toxicant interactions and critiques global regulatory shortcomings, underscoring the real-world consequences through case studies on PFAS, heavy metals, and pesticide mixtures. It advocates for a paradigm shift, proposing reforms that integrate emerging tools like exposomics and computational toxicology with holistic frameworks such as One Health. We highlight pioneering regulatory efforts, including Canada's mandate for cumulative risk assessments under CEPA and the EU's development of mixture assessment factors (MAFs), as essential models for progress. Our recommendations include mandating science-based mixture assessments, harmonizing global standards, and implementing equity-driven policies to align regulations with the reality of multichemical exposures.

PMID:41985101 | DOI:10.1021/acs.chemrestox.5c00375

Chem Res Toxicol. 2026 Apr 15. doi: 10.1021/acs.chemrestox.5c00375. Online ahead of print.

ABSTRACT

Human and environmental health are critically threatened by combined exposures to multiple chemical toxicants, including industrial chemicals, heavy metals, pesticides, endocrine-disrupting chemicals (EDCs), and per- and polyfluoroalkyl substances (PFAS). These substances interact biologically, producing additive, synergistic, or antagonistic effects that conventional single-substance risk assessments fail to predict. This leads to a systematic underestimation of health risks, particularly for vulnerable populations. Despite robust evidence on mixture toxicity, major regulatory frameworks such as the US Toxic Substances Control Act (TSCA) and the EU's REACH program continue to assess chemicals in isolation. This review synthesizes current science on toxicant interactions and critiques global regulatory shortcomings, underscoring the real-world consequences through case studies on PFAS, heavy metals, and pesticide mixtures. It advocates for a paradigm shift, proposing reforms that integrate emerging tools like exposomics and computational toxicology with holistic frameworks such as One Health. We highlight pioneering regulatory efforts, including Canada's mandate for cumulative risk assessments under CEPA and the EU's development of mixture assessment factors (MAFs), as essential models for progress. Our recommendations include mandating science-based mixture assessments, harmonizing global standards, and implementing equity-driven policies to align regulations with the reality of multichemical exposures.

PMID:41985101 | DOI:10.1021/acs.chemrestox.5c00375

Free Radic Biol Med. 2026 Apr 13:S0891-5849(26)00309-6. doi: 10.1016/j.freeradbiomed.2026.04.025. Online ahead of print.

ABSTRACT

Bisphenol A (BPA), a pervasive endocrine-disrupting chemical, has been increasingly implicated in thyroid carcinogenesis, yet the links between redox imbalance and metabolic alterations remain incompletely defined. Here, we combined LC-MS/MS quantification of BPA and its major conjugates with in vitro and in vivo thyroid cancer models to examine oxidative stress markers and lipid indices assessed by targeted biochemical assays and to evaluate a curcumin-modified, quercetin-loaded chitosan nanomicelle system (Que@CSNPs-Cur). We observed BPA enrichment in tumor-bearing mice, accompanied by increased lipid indices (free fatty acids, triglycerides, and total cholesterol) and elevated oxidative stress markers (ROS, TOS, and MDA), as assessed by targeted enzymatic and colorimetric assays. At the molecular level, BPA exposure was associated with reduced PTEN expression and increased PI3K/AKT phosphorylation, consistent with enhanced proliferative and invasive phenotypes in papillary thyroid carcinoma cells. Que@CSNPs-Cur restored PTEN levels, reduced PI3K/AKT activation, attenuated redox and lipid indices, and promoted caspase-3-dependent apoptosis. In xenograft mice, Que@CSNPs-Cur suppressed tumor growth, decreased oxidative stress markers and lipid indices, and reduced tumor BPA residue. Collectively, these results suggest that BPA exposure is linked to PTEN/PI3K/AKT dysregulation, oxidative stress and lipid disturbances. Que@CSNPs-Cur is a promising redox-oriented nanotherapeutic strategy for BPA-associated thyroid cancer phenotypes. Notably, the present study does not determine whether oxidative stress is upstream or downstream of PTEN suppression.

PMID:41985638 | DOI:10.1016/j.freeradbiomed.2026.04.025

Environ Toxicol. 2026 Apr 15. doi: 10.1002/tox.70094. Online ahead of print.

ABSTRACT

Urban coastal lagoons are highly vulnerable ecosystems increasingly affected by metal contamination, as well as multiple anthropogenic stressors. This study evaluated ecotoxicological and human health risks associated with chronic metal exposure in Nile tilapia (Oreochromis niloticus) from an anthropogenically impacted lagoon in southeastern Brazil. Monitoring was conducted over one year (2022-2023) across four seasonal campaigns. Fifty-seven tilapia specimens were collected during dry and rainy seasons, and liver and muscle tissue were analyzed for antioxidant biomarkers (superoxide dismutase-SOD, glutathione S-transferase-GST, reduced glutathione-GSH, total antioxidant capacity-TAC), oxidative damage (lipid peroxidation-LPO, protein carbonyl-PTC), and metal detoxification (metallothionein-MT). Endocrine disruption was assessed via plasma vitellogenin (VTG), and human health risks were estimated. Metal and metalloid diversity was higher in the dry season (12 vs. 7 elements), with some sites (P1-P3) presenting critical levels. Metals and metalloids in MT-enriched subcellular tissue fractions revealed seasonal shifts in As, Co, Rb, and Se, with Cd, Hg, and Pb detected only in liver during the dry period. Sex differences observed regarding GSI (females > males; p ≤ 0.05) aligned with higher male VTG levels. Antioxidant responses were higher in the dry season (hepatic SOD +81.9%), while oxidative damage increased substantially in both tissues (muscle +75.7%, liver +79.6%). The applied integrated biomarker-metal approach revealed a clear dry-season intensification of metal and metalloid exposure and biological responses, emphasizing endocrine and oxidative alterations and highlighting the need for seasonal biomonitoring efforts.

PMID:41986105 | DOI:10.1002/tox.70094

Int J Mol Sci. 2026 Mar 25;27(7):2978. doi: 10.3390/ijms27072978.

ABSTRACT

Bisphenol A (BPA) is a widespread endocrine disruptor that interferes with metabolism in humans and animals by inducing oxidative stress, lipid peroxidation, and cell death. Probiotics, conversely, have shown potential in promoting host health and reducing the toxicity of endocrine-disrupting chemicals (EDCs). This study examined whether sub-chronic BPA exposure disrupts hepatic lipid metabolism in female zebrafish (Danio rerio), and whether co-administration of probiotics mitigates these effects. Adult females were exposed for 28 days to the following treatments: 10 µg/L BPA via water (BPA); 10⁹ CFU/g body weight/day of probiotic formulation (P); and both treatments (BPA+P). An untreated group served as a control (CTRL). Hepatic lipid composition was analyzed using UHPLC-QTOF-MS, while liver sections were investigated by Fourier Transform Infrared Imaging (FTIRI) spectroscopy. BPA exposure decreased 14 unsaturated triacylglycerols and lysophosphatidylcholine 18:0, suggesting steatosis onset and inflammation, while in the group exposed to BPA+P, the decrease was limited to 8 triacylglycerols and the reduction in lysophosphatidylcholine 18:0 was prevented. Analyses of pooled liver samples precluded modeling tank-level effects; thus, the results are interpreted as semi-quantitative. Partial least square discriminant analysis built on the comparison of all groups together confirmed an intermediate phenotype for BPA+P fish between BPA and P groups. The observed beneficial role of probiotics in counteracting BPA-related metabolic disturbances was also supported by FTIRI, evidencing the ability to mitigate the effects of BPA on lipid and glycosylated compound metabolism. These findings highlight the potential of probiotic supplementation as a practical and accessible strategy to mitigate BPA-induced metabolic disturbances, contributing to the development of mitigating approaches against environmental contaminant-related liver dysfunction.

PMID:41977165 | PMC:PMC13073630 | DOI:10.3390/ijms27072978

Int J Mol Sci. 2026 Apr 5;27(7):3299. doi: 10.3390/ijms27073299.

ABSTRACT

Bisphenol A (BPA) has long been used in plastics, resins, and food packaging materials; however, extensive research has demonstrated its reproductive, developmental, and endocrine-disrupting effects. Consequently, BPA has been increasingly restricted and replaced with structural analogues. Among these, tetramethyl bisphenol F (TMBPF) has emerged as one of the most widely used substitutes, particularly in epoxy resins and food-can coatings. Although initially regarded as a safer alternative, accumulating evidence suggests that TMBPF may exert multiple toxicological effects, raising concerns about its potential developmental neurotoxicity. The present study aimed to investigate the neurodevelopmental effects of TMBPF using both in vitro and in vivo approaches. First, a developmental neurotoxicity assay employing Sox1-GFP mouse embryonic stem cells was used to evaluate cytotoxicity using the cell counting kit-8 assay and neural differentiation based on green fluorescent protein (GFP) fluorescence intensity. The results indicated developmental neurotoxic potential according to the established discrimination index. Subsequently, pregnant and lactating mice were exposed to TMBPF daily from gestational day 10.5 to postnatal day 20, and their offspring were assessed for behavioral performance as well as changes in the expression of neurodevelopment-related genes in the brain. Behavioral analyses encompassed multiple domains, including memory and learning, social behavior, anxiety-related responses, and spontaneous locomotor activity, suggesting alterations in these functional outcomes. Molecular analyses further demonstrated changes associated with dopaminergic and cholinergic signaling, synaptic plasticity, neuronal activity markers, neuropeptides, and inflammatory pathways. Collectively, these findings provide the first evidence in a mammalian model that maternal exposure to TMBPF may influence offspring neurodevelopment. These findings suggest potential implications for human exposure to TMBPF, particularly through food-contact materials, and warrant further mechanistic and dose-response studies.

PMID:41977478 | PMC:PMC13072762 | DOI:10.3390/ijms27073299

Chemosphere. 2026 Apr 13;402:144928. doi: 10.1016/j.chemosphere.2026.144928. Online ahead of print.

ABSTRACT

Mercury (Hg) pollution remains a pervasive global environmental health challenge due to its persistence, long-range atmospheric transport, and capacity for biogeochemical transformation into highly toxic and bioavailable forms, particularly methylmercury (MeHg). This review synthesises current knowledge on Hg sources, environmental fate, multi-trophic bioaccumulation, and health impacts, organised within a One Health framework that explicitly links ecosystem contamination, wildlife toxicity, and human disease. Anthropogenic activities now dominate global Hg emissions, driving contamination of aquatic, terrestrial, and agroecosystems far beyond emission hotspots. Microbial methylation in sediments, wetlands, and rice paddies facilitates the production of bioavailable MeHg that undergoes efficient biomagnification of MeHg across food webs, resulting in elevated burdens in fish, wildlife, and human populations reliant on seafood and rice-based diets. Evidence across taxa demonstrates that Hg toxicity is underpinned by conserved molecular mechanisms, including oxidative stress, mitochondrial dysfunction, trace element disruption, endocrine interference, and epigenetic alteration, supporting cross-species extrapolation of risk. In humans, chronic exposure is associated with neurodevelopmental impairment, cardiovascular disease, renal toxicity, immune dysregulation, and intergenerational effects, with disproportionate impacts on vulnerable and socioeconomically marginalised populations. While remediation technologies, emission controls, and international agreements such as the Minamata Convention have reduced some contemporary sources, large reservoirs of legacy Hg in soils, sediments, and biota continue to sustain exposure risks. This review highlights critical knowledge gaps related to climate-mercury interactions, low-dose chronic effects, and combined stressors, and argues that effective Hg prevention and governance require integrated surveillance, mechanistic toxicology, food-system-based interventions, and equity-focused policies within a One Health paradigm.

PMID:41980442 | DOI:10.1016/j.chemosphere.2026.144928

Chem Biol Interact. 2026 Apr 12:112081. doi: 10.1016/j.cbi.2026.112081. Online ahead of print.

ABSTRACT

Diphenyltin (DPT) is an organotin and an endocrine disruptor, impairing the male reproductive system. However, the effect of DPT on Leydig cell function during puberty remains unknown. DPT exhibits selective testicular toxicity without altering gross reproductive organ weights. In rats administered 2.5-10 mg/kg DPT from postnatal day 35 to 57, serum testosterone levels were significantly reduced at 5 and 10 mg/kg, while luteinizing hormone and follicle-stimulating hormone levels remained unchanged. Histological and immunohistochemical analyses revealed decreased Leydig cell numbers and reduced expression of steroidogenic markers (STAR, LHCGR, SCARB1, CYP11A1, and INSL3). Testicular oxidative stress was evident, with downregulated SOD1, SOD2, and CAT and elevated malondialdehyde. Autophagy markers (LC3B, Beclin1) were upregulated alongside decreased phosphorylated mTOR, as well as increased 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, and LC3B staining in Leydig cells, suggesting oxidative stress-induced autophagy. In vitro, adult Leydig cells displayed ROS accumulation, mitochondrial membrane potential loss, and autophagosome formation. In adult Leydig cells, DPT enhanced mitochondrial fission by upregulating DRP1 and FIS1, downregulating MFN1, and activating PINK1-PARKIN-mediated mitophagy. The fission inhibitor mdivi-1 mitigated mitochondrial fragmentation, decreased mitophagy, and partially restored steroidogenesis. These findings indicate that DPT disrupts Leydig cell function through oxidative stress, mitochondrial fission, and mitophagy, ultimately leading to testosterone suppression and compromised sperm production. Therapeutic targeting of mitochondrial dynamics may protect steroidogenic cells from toxin-induced damage.

PMID:41980619 | DOI:10.1016/j.cbi.2026.112081

J Hazard Mater. 2026 Apr 10;509:142018. doi: 10.1016/j.jhazmat.2026.142018. Online ahead of print.

ABSTRACT

Despite the remoteness of their breeding sites, subantarctic seabirds are susceptible to anthropogenic pollutants (e.g. microplastics) and other chemical stressors (e.g. plastic additives) that are released from ships and research stations, arrive in ocean currents, are transported in the atmosphere, or are ingested when the birds feed north of the Antarctic Polar Front. In this study, we investigated the presence and levels of microplastics and several groups of endocrine-disrupting chemicals (EDCs) in adults or chicks of seven seabird species breeding at the subantarctic islands of South Georgia. A total of 1275 anthropogenic particles were recovered in the gastrointestinal tracts of 76 seabirds, with a frequency of occurrence of 97.4%, a mean value of 16.78 ± 18.79 particles per individual and of 0.03 ± 0.03 particles/g body weight. Ten percent (n = 130 particles) of the particles were identified chemically using microFTIR spectroscopy, of which 59% were synthetic, 18% were natural, 19% were anthropogenic unknown and 4% were anthropogenic cellulosic. Of the EDCs, only polybrominated diphenyl ethers (PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) congeners occurred at levels above the limit of quantification. Liver samples consistently exhibited the highest concentrations of both contaminant groups. The highest concentrations of PBDEs were in adult brown skuas (133.96 ng/g) and of MeO-PBDEs were in wandering albatross chicks (6.50 ng/g). This research provides evidence of plastics and plastic additives in subantarctic seabirds, underscoring the need to strengthen measures aimed at reducing marine pollution.

PMID:41980382 | DOI:10.1016/j.jhazmat.2026.142018

Animals (Basel). 2026 Apr 1;16(7):1073. doi: 10.3390/ani16071073.

ABSTRACT

The brown trout (Salmo trutta) is a commercially and ecologically significant salmonid fish, yet its hepatic cellular and functional dynamics throughout the reproductive cycle remain poorly characterised, particularly in males. This study investigated seasonal and sex-specific liver plasticity across four reproductive stages: spawning capable (December), regressing (March), regenerating (July), and developing (November). We quantified mRNA and protein abundance of key oestrogen-responsive targets-vitellogenin (VtgA) and zona pellucida (ZP) proteins-alongside cell turnover markers, caspase 3 (Casp3) and proliferating cell nuclear antigen (PCNA). These molecular endpoints were integrated with stereological analyses to estimate hepatocyte, nuclear, and cytoplasmic volumes. Results revealed stage-dependent mobilisation and transient hepatic retention of reproductive proteins; females exhibited stronger vitellogenic signatures and more pronounced seasonal shifts than males. Although VtgA and ZP mRNA levels peaked during the developing and spawning-capable stages, males maintained low but consistent levels throughout the cycle, indicating constitutive hepatic oestrogen sensitivity. Regarding cell turnover, PCNA protein data indicated heightened proliferative activity during the spawning-capable and regressing stages. In contrast, while Casp3 mRNA levels remained stable across all stages, protein detection suggested a post-transcriptional increase in apoptotic signalling during the developing phase, consistent with controlled tissue remodelling rather than extensive cell loss. Stereological data confirmed enlarged hepatocyte and nuclear volumes during periods of high secretory and proliferative demand. Overall, these findings demonstrate significant stage-dependent and sex-specific plasticity in brown trout liver, providing a robust reference framework for ecological monitoring, endocrine disruption assessments, and studies of teleost reproductive physiology.

PMID:41976051 | PMC:PMC13072334 | DOI:10.3390/ani16071073

J Hazard Mater. 2026 Apr 10;509:142018. doi: 10.1016/j.jhazmat.2026.142018. Online ahead of print.

ABSTRACT

Despite the remoteness of their breeding sites, subantarctic seabirds are susceptible to anthropogenic pollutants (e.g. microplastics) and other chemical stressors (e.g. plastic additives) that are released from ships and research stations, arrive in ocean currents, are transported in the atmosphere, or are ingested when the birds feed north of the Antarctic Polar Front. In this study, we investigated the presence and levels of microplastics and several groups of endocrine-disrupting chemicals (EDCs) in adults or chicks of seven seabird species breeding at the subantarctic islands of South Georgia. A total of 1275 anthropogenic particles were recovered in the gastrointestinal tracts of 76 seabirds, with a frequency of occurrence of 97.4%, a mean value of 16.78 ± 18.79 particles per individual and of 0.03 ± 0.03 particles/g body weight. Ten percent (n = 130 particles) of the particles were identified chemically using microFTIR spectroscopy, of which 59% were synthetic, 18% were natural, 19% were anthropogenic unknown and 4% were anthropogenic cellulosic. Of the EDCs, only polybrominated diphenyl ethers (PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) congeners occurred at levels above the limit of quantification. Liver samples consistently exhibited the highest concentrations of both contaminant groups. The highest concentrations of PBDEs were in adult brown skuas (133.96 ng/g) and of MeO-PBDEs were in wandering albatross chicks (6.50 ng/g). This research provides evidence of plastics and plastic additives in subantarctic seabirds, underscoring the need to strengthen measures aimed at reducing marine pollution.

PMID:41980382 | DOI:10.1016/j.jhazmat.2026.142018

Int Med Case Rep J. 2026 Apr 7;19:562039. doi: 10.2147/IMCRJ.S562039. eCollection 2026.

ABSTRACT

Secondary amenorrhea is commonly associated with endocrine or gynecological disorders; however, central nervous system diseases may also disrupt the hypothalamic-pituitary-ovarian (HPO) axis and lead to hypogonadotropic hypogonadism. Hydrocephalus caused by tuberculous meningitis represents a rare but important neurological cause of menstrual disturbance. We report the case of a 24-year-old Indonesian woman of Southeast Asian ethnicity presenting with secondary amenorrhea for 2.5 years following a history of tuberculous meningitis complicated by communicating hydrocephalus and ventriculoperitoneal shunt placement. Hormonal evaluation revealed low gonadotropin and estradiol levels consistent with hypogonadotropic hypogonadism. Neuroimaging demonstrated ischemic lesions involving the thalamic and basal ganglia regions with radiological features of hydrocephalus and tuberculoma-related meningeal enhancement. Transrectal ultrasonography showed preserved ovarian morphology with antral follicles, supporting a central rather than ovarian etiology. Bone mineral density assessment revealed reduced bone mass associated with prolonged hypoestrogenism. A review of the literature highlights several proposed mechanisms linking hydrocephalus and hypothalamic dysfunction, including increased intracranial pressure and structural compression of hypothalamic pathways. This case emphasizes that neurological conditions such as tuberculous meningitis with hydrocephalus may cause secondary amenorrhea through disruption of hypothalamic-pituitary regulation. Early recognition of neuroendocrine complications is essential to prevent delayed diagnosis and long-term reproductive or metabolic consequences.

PMID:41969396 | PMC:PMC13069941 | DOI:10.2147/IMCRJ.S562039

Se Pu. 2026 Apr;44(4):413-421. doi: 10.3724/SP.J.1123.2025.08001.

ABSTRACT

Ultraviolet （UV） absorbers are a group of chemicals widely used in various industrial and consumer products， such as plastics， coatings， and personal care products， to protect against UV radiation. Among them， benzotriazole derivatives （e.g. UV-326， UV-327， UV-328， UV-329， and UV-P） are the most frequently employed. Owing to their widespread use and potential persistence in the environment， these compounds have been detected in various environmental matrices， including surface water， wastewater， sediment， and biota. Certain UV stabilizers have been reported to exhibit endocrine-disrupting properties and pose potential ecological risks. Therefore， developing sensitive and reliable analytical methods for monitoring these compounds in environmental samples is essential. To address the need for reliable detection methods， this study developed a robust method based on liquid-liquid extraction （LLE） coupled with ultra performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-MS/MS） for the simultaneous determination of eight UV absorbers in surface water and wastewater. Critical optimization of the pretreatment process focused on solvent selection and purification parameters. The finalized protocol involved extracting 100 mL water samples twice with dichloromethane. After nitrogen-assisted solvent evaporation， the residue was reconstituted in methanol and mixed with the internal standard solution. UPLC-MS/MS parameters were optimized to achieve optimal instrumental performance. The separation of the eight UVs was performed using a BEH C18 column （100 mm × 2.1 mm， 1.7 μm） with a gradient elution system consisting of 0.2% （mass fraction） formic acid aqueous solution and acetonitrile at a flow rate of 0.4 mL/min. The injection volume was 2 μL. Detection was performed in positive ion mode using multiple reaction monitoring （MRM）， with an electrospray ionization voltage set at 5 500 V. Quantification was achieved via internal standard calibration to ensure precision and accuracy. The method demonstrated excellent linearity for all target compounds across their respective concentration ranges， with a correlation coefficient （r）>0.995. The method detection limits （MDLs） ranged from 1.3 ng/L to 2.8 ng/L， indicating high sensitivity. Recovery tests conducted at low， medium， and high spiking levels （20， 200， and 800 ng/L） yielded recoveries of 80.3%-117.8%， with relative standard deviations （RSDs） of 1.4%-10.5%， confirming the method's robustness across different sample matrices. Application of the method to 10 textile dyeing wastewater samples revealed the presence of four UV absorbers： UV-329， UV-326， UV-328， and UV-350. Notably， UV-329 showed the highest detection frequency and accounted for 85% of the total detected mass concentrations， ranging from 5.2 to 2 109 ng/L. Its prevalence suggests its widespread use in industrial processes and potential persistence in aquatic environments. In conclusion， the developed method is highly sensitive， accurate， and reliable for detecting UV absorbers in environmental water samples. Its successful application to surface water and wastewater analysis provides a valuable tool for monitoring these emerging contaminants， thereby supporting the assessment of their environmental and health risks. This study highlights the importance of continued monitoring and regulation of UV absorbers to mitigate their potential adverse effects on ecosystems and human health.

PMID:41969259 | PMC:PMC13077533 | DOI:10.3724/SP.J.1123.2025.08001

Evol Appl. 2026 Apr 10;19(4):e70226. doi: 10.1111/eva.70226. eCollection 2026 Apr.

ABSTRACT

Persistent pathological structures, such as tumors, fibrotic nodules, granulomas, microbial biofilms, or protein aggregates, are traditionally viewed as age-related conditions that emerge after reproduction, when natural selection is less effective at eliminating traits expressed late in life. However, some pathologies with robust and organized architectures can arise surprisingly early, challenging this classical perspective. We recently proposed that intra-organismal selection for function, a selective process operating within organisms and acting on non-reproducing entities by favoring structural configurations that enhance stability, robustness, and novelty generation, may play a role in aging. Here, we suggest that this same process can also operate well before the so-called selection shadow (i.e., life stages where natural selection is too weak to purge deleterious mutations). We identify three non-mutually exclusive mechanisms that may promote this early-life action: (i) initial local adaptive benefits, such as improved tissue repair or containment of infection; (ii) limited or context-specific fitness costs, allowing structurally stable but abnormal configurations to persist undetected; and (iii) rapid environmental changes that reshape tissue-level selective landscapes, driven by pollutants, endocrine disruptors, or novel diets. Recognizing early-onset organized pathologies as by-products of eco-evolutionary tissue dynamics, rather than as mere developmental errors, reframes their biological significance and opens new therapeutic avenues. Instead of targeting cells exclusively, future strategies could focus on disrupting the functional architecture of pathological tissues and structures, offering novel means to prevent or control early-life diseases shaped by internal selection forces.

PMID:41970166 | PMC:PMC13067062 | DOI:10.1111/eva.70226

Front Cell Dev Biol. 2026 Mar 27;14:1729897. doi: 10.3389/fcell.2026.1729897. eCollection 2026.

ABSTRACT

This review systematically examines the underlying mechanisms linking erectile dysfunction (ED) with arthritis and explores multidisciplinary management strategies. Epidemiological studies confirm that patients with various arthritis-including osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gouty arthritis-exhibit significantly higher ED prevalence and incidence risks compared to the general population. This association remains independent of confounding factors such as age and comorbidities. Core mechanisms linking the two include chronic inflammation disrupting the "NO-cGMP-PKG" erectile molecular axis, vascular endothelial dysfunction causing insufficient penile blood supply, endocrine-metabolic disorders (e.g., insulin resistance, reduced testosterone), neuropsychological factors (anxiety, depression, chronic pain), and the synergistic effects of therapeutic agents (methotrexate, nonsteroidal anti-inflammatory drugs, glucocorticoids). Clinical recommendations advocate an "active screening-tiered assessment" approach, utilizing the International Index of Erectile Function (IIEF) combined with disease activity tools (e.g., DAS28, BASDAI) for screening and evaluation. Management should follow a multidisciplinary team (MDT) model integrating "control of underlying disease + individualized ED treatment + psychological intervention + lifestyle optimization" to improve patients' overall health outcomes ultimately.

PMID:41970951 | PMC:PMC13066131 | DOI:10.3389/fcell.2026.1729897

Front Cell Dev Biol. 2026 Mar 27;14:1768139. doi: 10.3389/fcell.2026.1768139. eCollection 2026.

ABSTRACT

BACKGROUND: In recent years, growing attention has been paid to the role of Benzo [a]pyrene (BaP) in the development and progression of prostate cancer (PCa). However, the specific molecular mechanisms remain unclear. This study aims to explore the potential association between BaP and PCa and to identify key molecular targets that may underlie this relationship, using an integrative bioinformatics approach.

METHODS: This study initiated with a computational toxicology assessment of BaP's carcinogenicity and endocrine-disrupting properties using the ProTox 3.0 platform. Subsequently, potential target genes linking BaP to PCa were identified by integrating multiple public databases. The overlapping genes underwent PPI network construction and visualization, followed by GO functional annotation and KEGG pathway enrichment analyses to elucidate the underlying biological mechanisms. Through screening 101 machine learning algorithm combinations, we identified the most relevant key genes associated with PCa progression. Molecular docking technology was then employed to evaluate the binding interactions between BaP/natural active products and these key targets. The CIBERSORT algorithm was utilized to analyze RRM2's regulatory role in the PCa tumor microenvironment, complemented by pan-cancer analysis to investigate RRM2's universal functions across various malignancies. Finally, in vitro cell experiments were conducted for validation.

RESULTS: This study further underscores the carcinogenic properties and endocrine-disrupting effects of BaP. Integration of multi-source databases identified 443 potential BaP-PCa targets. GO and KEGG enrichment analyses revealed that these targets are primarily involved in regulating cell proliferation, inflammatory responses, oxidative stress, and multiple oncogenic signaling pathways. Machine learning algorithm screening showed that the Enet (α = 0.1) model exhibited the best predictive performance and robustness. Through molecular docking, Kaplan-Meier survival analysis, and validation using the Human Protein Atlas (HPA) database, RRM2 was identified as a key regulatory gene and found to play a central role in BaP-mediated immunosuppression processes. Pan-cancer analysis demonstrated that RRM2 has universal functions across various malignancies. Molecular docking results indicated that seven known anti-tumor natural products exhibit significant binding affinity with RRM2. In vitro experiments demonstrated that BaP treatment was associated with increased RRM2 expression in prostate cancer cells, while baicalin treatment reduced this effect, providing preliminary experimental support for the bioinformatic predictions.

CONCLUSION: This study delineates a potential mechanistic framework by which BaP may be associated with PCa progression through multi-target and multi-pathway mechanisms, highlighting RRM2 as a candidate core mediator. These findings provide a theoretical foundation for future experimental validation and epidemiological studies.

PMID:41970950 | PMC:PMC13066230 | DOI:10.3389/fcell.2026.1768139

Front Endocrinol (Lausanne). 2026 Mar 26;17:1761556. doi: 10.3389/fendo.2026.1761556. eCollection 2026.

ABSTRACT

Heavy metals are increasingly recognized as endocrine-disrupting chemicals (EDCs) capable of perturbing neurodevelopment and cognition across multiple generations. Among these, methylmercury (MeHg), lead (Pb), and cadmium (Cd) remain global public health concerns due to their environmental persistence, bioaccumulation in food and water sources, and widespread human exposure. Evidence from epidemiological and experimental studies demonstrates that these metals can interfere with hormonal signaling, neurogenesis, synaptic organization, neuroendocrine regulation and epigenetic programming-processes that are essential for learning and memory formation during critical developmental windows. Collectively, current evidence supports the view that MeHg, Pb, and Cd exposure act as potent neuroendocrine disruptors capable of producing intergenerational consequences on learning and memory. In this review, we highlight the recent findings of the effects of prenatal exposure to the three heavy metals (i.e., MeHg, Pg and Cd) on developing learning and memory.

PMID:41970999 | PMC:PMC13061712 | DOI:10.3389/fendo.2026.1761556

Fish Physiol Biochem. 2026 Apr 13;52(2):62. doi: 10.1007/s10695-026-01680-6.

ABSTRACT

Synthetic detergents including Linear alkylbenzene sulfonates (LAS) and Branched alkylbenzene sulfonates (BAS) are commonly used in household and industrial cleaning products, yet their chronic toxicological effects on freshwater fish species remain inadequately explored. The current study investigates the sub-lethal effects of these synthetic detergents on hemato-biochemical profile of freshwater fish Labeo rohita. The 96-h LC₅₀ values of LAS and BAS for the selected fish were calculated as 6.45 mg/L and 8.31 mg/L, respectively, using the probit analysis method. A total of 180 fish specimens were randomly subjected to a triplicate experimental setup, with 60 fish allocated to each replicate, marked as G₀, G₁, G₂ ang G₃ where G₀ served as control while the remaining three groups were treated with LAS (3.22 mg/L), BAS (4.15 mg/L) and their binary mixture (LAS, 1.61 mg/L + BAS, 2.7 mg/L) respectively, for a period of 30 days. Post exposure analysis revealed a significant reduction (p < 0.05) in the RBCs, hemoglobin, and hematocrit value with increase in WBCs and platelets count in detergents exposed fish, compared to control. Among endocrine hormones T3, T4 and insulin levels decreased significantly (p < 0.05), while TSH and Cortisol were increased in the detergents exposed fish. Blood levels of NO, IgM, and RB were significantly decreased (p < 0.05) in all detergent treated fish, whereas lysozyme activity was significantly increased only in the LAS and mixture detergent treated fish. Antioxidant biomarkers, including CAT, SOD, and GSH, were significantly decreased (p < 0.05), whereas MDA levels showed a marked increase in detergents exposed fish. Histopathological analysis identified substantial alterations in gill tissues across all the detergents exposed groups. Furthermore, genotoxic analysis demonstrated a significant (p < 0.05) increase in micronuclei (MNs) and erythrocytic nuclear abnormalities (ENAs), confirming the genotoxic potential of the tested detergents. These findings suggest that chronic exposure to commonly used detergents can disrupt multiple physiological systems in L. rohita, highlighting the potential ecological risks of detergent pollution in freshwater ecosystems.

PMID:41973146 | DOI:10.1007/s10695-026-01680-6

Physiol Rev. 2026 Apr 13. doi: 10.1152/physrev.00035.2025. Online ahead of print.

ABSTRACT

Burn injuries are among the most devastating disruptors of human physiology, provoking systemic disturbances unmatched by nearly any other form of pathology, yet they remain critically underappreciated. Each year, approximately 8.4 million people sustain burn injuries worldwide, leading to 110,000 deaths and countless cases of long-term disability. Beyond the immediate tissue damage, burns trigger a uniquely severe and persistent hypermetabolic response that, if not effectively managed, cascades into widespread dysfunction across multiple organ systems, driving morbidity and, in many cases, mortality. Among the many affected organ systems is the endocrine system, which when disrupted, leads to compromised fluid and mineral balance, cachexia, insulin resistance, immunosuppression, and various other health issues. In this narrative literature review, we highlight the various endocrine axes and how they are dysregulated by thermal injury, and the current pharmacological strategies that are used to treat these burn-induced hormone disruptions and hypermetabolism. Taking into account the widespread effects of the endocrine system, we also delve into the intricate interplay between the endocrine and immune systems of each axis, highlighting the substantial challenge of immunosuppression often observed in severe burn patients. Additionally, we underline the current gaps that exist in the literature and the urgent need for long-term longitudinal trials that take factors such as age and sex into consideration. A better understanding of the implications of burns on the endocrine system will help with the development of effective treatments that could improve long-term health of severe burn patients.

PMID:41973596 | DOI:10.1152/physrev.00035.2025

J Vis Exp. 2026 Mar 24;(229). doi: 10.3791/70242.

ABSTRACT

Chronic low-dose exposure to bisphenol A (BPA), a widely used environmental endocrine disruptor, has been increasingly associated with oxidative stress-mediated neurotoxicity. Thymoquinone (TQ), a bioactive constituent of Nigella sativa, exhibits potent antioxidant properties; however, its neuroprotective potential against BPA-induced toxicity remains incompletely understood. Given the pervasive nature of BPA exposure, identifying effective and accessible neuroprotective strategies is of growing importance. This study investigated the effects of TQ on oxidative stress, Keap-1/Nrf-2 signaling, behavior, and histopathological alterations in rats exposed to BPA. A total of 24 adult male Wistar Albino rats were randomly assigned to four groups (n = 6/group): control, BPA, BPA + 10 mg/kg TQ (BPA+TQ I), and BPA + 20 mg/kg TQ (BPA+TQ II). BPA (50 µg/kg) and TQ were administered intragastrically for 30 days. BPA exposure induced significant behavioral impairments, oxidative stress, disruption of Keap-1/Nrf-2 signaling, and marked histopathological damage in the hippocampus and cerebral cortex. TQ treatment significantly improved locomotor activity and depression-like behavior, reduced lipid peroxidation and nitric oxide levels, restored glutathione-related antioxidant capacity, and normalized Keap-1 and Nrf-2 expression (p < 0.001). These protective effects were more pronounced at the higher TQ dose. Taken together, these findings demonstrate that thymoquinone mitigates BPA-induced neurotoxicity through modulation of oxidative stress and the Keap-1/Nrf-2 signaling pathway, highlighting its potential as a neuroprotective agent against environmentally relevant BPA exposure.

PMID:41973694 | DOI:10.3791/70242

Bioorg Chem. 2026 Apr 9;176:109850. doi: 10.1016/j.bioorg.2026.109850. Online ahead of print.

ABSTRACT

Biocide disinfectants are essential chemicals in infection control, but their use may cause adverse effects by inhibiting neurosteroid biosynthesis. In the current study we systematically examine the inhibitory effect of the biocide benzalkonium chloride (BAC), which is widely used for surface disinfection and as preservative in many consumer products, on human and rat 5α-reductase 1 (5α-R1) activity. The effects of BAC component (C1-C18) on brain 5α-R1 were investigated using HPLC-MS/MS measurement of steroid substrate testosterone and product dihydrotestosterone for enzyme inhibition screening assay and kinetics analysis, surface plasmon resonance (SPR) binding, intact cells, in silico docking and molecular dynamic simulations as well as structure-activity relationship (SAR)/3D-QSAR modeling. BAC component inhibited both human and rat 5α-R1, depending on alkyl chain length, with C10⁺ components exhibiting significant activity. C18 component emerged as the most potent inhibitor (IC₅₀ = 9.54 μM for human 5α-R1; 34.36 μM for rat 5α-R1). SPR assay showed that C18 had a high affinity binding with KD of 6.42 μM with a relatively slow dissociation rate, indicating stable target engagement once bound. Mechanistic studies identified mixed/noncompetitive inhibition of 5α-R1 by BAC components by competing with NADPH (SPR assay). In intact SF126 cells, C12-C18 components suppressed 5α-dihydrotestosterone formation at 10-100 μM. Pearson correlation analysis linked inhibitory strength to structural parameters (LogP, molecular weight, alkyl carbon count, heavy atoms, and rotatable bonds). A 3D-QSAR pharmacophore model highlighted hydrophobic interactions as critical for inhibition. Molecular docking further elucidated binding mechanisms, showing that BAC components occupy the NADPH-binding site via van der Waals forces, hydrogen bonds, hydrophobic contacts, and charge interactions. Our results suggest that BAC components have the potential to inhibit human and rat 5α-R1 activity and cause the neural disorders. These findings underscore BAC as potential endocrine disruptor by targeting neurosteroid biosynthesis, warranting further investigation into their neurotoxicological implications. This work was funded by the Zhejiang Nature and Science Foundation. The funders had no role in study design, interpretation or decision to publish.

PMID:41974091 | DOI:10.1016/j.bioorg.2026.109850

Environ Epigenet. 2026 Mar 17;12(1):dvag010. doi: 10.1093/eep/dvag010. eCollection 2026.

ABSTRACT

Bisphenol A (BPA), which is a common ingredient of plastics and epoxy resins, is among the most commonly found endocrine-disrupting chemicals in the human environment. Chronic human exposure has raised concerns over its effects on reproductive health. There is growing evidence showing that BPA causes epigenetic changes, primarily DNA methylation, histone changes, and non-coding RNA changes that result in hormonal imbalances, a disruption in gametogenesis, and fertility impairment. This review summarizes current understanding of how BPA alters male reproductive performance in exposed individuals, including impaired spermatogenesis and sperm quality, endocrine imbalance, and disruption of hypothalamic-pituitary-gonadal (HPG) signaling, often in concert with oxidative stress and altered steroidogenesis. We then discuss evidence that BPA exposure, especially during critical developmental windows, can reprogram the paternal germline, such that epigenetic alterations carried by sperm, such as DNA methylation changes, abnormal histone acetylation (H3K9ac, H3K27ac, H4K12ac), disrupted histone-to-protamine transition, and altered sperm small RNAs/miRNA profiles, can contribute to fertility defects in subsequent generations. Moreover, various therapeutic methods, like epigenetic drugs and natural products such as resveratrol, naringenin, and genistein, are being studied to reverse or alleviate the impact of BPA. Given BPA's ubiquity, these findings also highlight the necessity of stricter regulation, health education to the general population, along with research into potential safer alternatives. Learning the ways BPA is remodeling the epigenome and fertility through generations is essential to protecting reproductive health and the basis of policy intervention.

PMID:41970605 | PMC:PMC13069567 | DOI:10.1093/eep/dvag010

Free Radic Biol Med. 2026 Apr 9;251:75-90. doi: 10.1016/j.freeradbiomed.2026.04.014. Online ahead of print.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent and heterogeneous endocrine-metabolic disorder affecting women of reproductive age, characterized by elevated androgen levels, disrupted ovulation, and polycystic ovarian changes. Increasing evidence indicates that oxidative stress and ferroptosis contribute to granulosa cell dysfunction and ovarian impairment in PCOS. In this study, we identified sestrin 2 (SESN2), a stress-inducible metabolic regulator, as a protective factor against ferroptosis in PCOS. Using both in vitro and in vivo PCOS models, we demonstrate that SESN2 deficiency aggravates oxidative stress and ferroptosis in ovarian granulosa cells. Mechanistically, loss of SESN2 reduced the overall lactylation level of peroxiredoxin 6 (PRDX6) and was associated with decreased lactylation at the K209 site, a modification important for PRDX6-mediated redox homeostasis. Quantitative co-immunoprecipitation showed that PRDX6 interacted with GPX4, and this interaction was markedly weakened by K209R mutation. Consistently, re-expression of wild-type PRDX6, but not the K209R mutant, substantially attenuated SESN2 deficiency-induced oxidative stress and ferroptotic injury. Overall, these findings indicate that SESN2 suppresses ferroptosis in PCOS at least partly by maintaining PRDX6 K209 lactylation, highlighting the SESN2-PRDX6 pathway as a potential therapeutic target for PCOS.

PMID:41966311 | DOI:10.1016/j.freeradbiomed.2026.04.014

Reprod Toxicol. 2026 Apr 9;143:109239. doi: 10.1016/j.reprotox.2026.109239. Online ahead of print.

ABSTRACT

Bisphenols and per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental endocrine-disrupting chemicals with widespread human exposure and growing concern regarding their reproductive toxicity. This review integrates current experimental and epidemiologic evidence to evaluate the potential endocrine-disrupting mechanisms and reproductive toxicity of bisphenols, particularly bisphenol A (BPA), and PFAS on female reproductive health. Available data demonstrate that these chemicals disrupt key hormonal and cellular processes regulating female reproduction, including hypothalamic-pituitary-ovarian axis signaling, ovarian steroidogenesis and folliculogenesis, oocyte quality and maturation, uterine structure and function, and oxidative stress. Across in vitro and animal models, BPA and PFAS consistently induce hormonal dysregulation, oxidative stress, mitochondrial dysfunction, and epigenetic alterations that impair coordinated ovarian-uterine signaling. Importantly, these mechanistic findings align with epidemiologic studies reporting associations between BPA and PFAS exposure and increased risk of adverse reproductive outcomes, including endometriosis, polycystic ovary syndrome, diminished ovarian reserve, premature ovarian insufficiency, infertility, and adverse pregnancy outcomes. Collectively, this review underscores the relevance of environmental chemical exposure as a modifiable risk factor for female reproductive health and emphasizes the need for further integration of mechanistic and population-based research to inform exposure assessment, risk evaluation, and regulatory strategies to reduce exposure to endocrine-disrupting chemicals and protect female reproductive health.

PMID:41966417 | DOI:10.1016/j.reprotox.2026.109239

Ecotoxicol Environ Saf. 2026 Apr 11;316:120124. doi: 10.1016/j.ecoenv.2026.120124. Online ahead of print.

ABSTRACT

This study aimed to investigate the association between per- and polyfluoroalkyl substances (PFAS) mixture exposure and hypertension risk, and to assess the mediating role of estradiol. We investigated these questions in 5175 adults from the U.S. National Health and Nutrition Examination Survey (NHANES 2011-2020). Serum concentrations of six PFAS and estradiol were quantified. Using weighted quantile sum (WQS) regression, we evaluated the joint effect of the PFAS mixture on hypertension (2017 ACC/AHA criteria). Restricted cubic splines (RCS) characterized exposure-response shapes, and causal mediation analysis tested estradiol as a potential mechanistic pathway. After full adjustment, perfluorononanoic acid (PFNA) exhibited the strongest association with hypertension (odds ratio per ln-unit increase, 1.16; 95% CI, 1.06-1.27). WQS regression identified PFNA as the primary driver of the mixture effect (weighted contribution, 37.5%). Crucially, estradiol significantly mediated 4.68% of the association between PFNA and hypertension, and 4.22% for perfluorooctanoic acid (PFOA). Sex-stratified analyses revealed that the associations of PFNA and PFOA with hypertension were significant only in females. All analyses accounted for the complex survey design and were adjusted for sociodemographic, lifestyle, and clinical factors. Our integrated analytical approach identifies PFNA, a long-chain PFAS, as a key driver of hypertension risk within environmental PFAS mixtures. The finding that estradiol reduction mediates this association provides novel evidence for an endocrine-disruption mechanism and explains observed female-specific susceptibility. These results highlight the importance of compound-specific prioritization and sex-aware frameworks in environmental risk assessment.

PMID:41967265 | DOI:10.1016/j.ecoenv.2026.120124

Reprod Toxicol. 2026 Apr 9;143:109239. doi: 10.1016/j.reprotox.2026.109239. Online ahead of print.

ABSTRACT

Bisphenols and per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental endocrine-disrupting chemicals with widespread human exposure and growing concern regarding their reproductive toxicity. This review integrates current experimental and epidemiologic evidence to evaluate the potential endocrine-disrupting mechanisms and reproductive toxicity of bisphenols, particularly bisphenol A (BPA), and PFAS on female reproductive health. Available data demonstrate that these chemicals disrupt key hormonal and cellular processes regulating female reproduction, including hypothalamic-pituitary-ovarian axis signaling, ovarian steroidogenesis and folliculogenesis, oocyte quality and maturation, uterine structure and function, and oxidative stress. Across in vitro and animal models, BPA and PFAS consistently induce hormonal dysregulation, oxidative stress, mitochondrial dysfunction, and epigenetic alterations that impair coordinated ovarian-uterine signaling. Importantly, these mechanistic findings align with epidemiologic studies reporting associations between BPA and PFAS exposure and increased risk of adverse reproductive outcomes, including endometriosis, polycystic ovary syndrome, diminished ovarian reserve, premature ovarian insufficiency, infertility, and adverse pregnancy outcomes. Collectively, this review underscores the relevance of environmental chemical exposure as a modifiable risk factor for female reproductive health and emphasizes the need for further integration of mechanistic and population-based research to inform exposure assessment, risk evaluation, and regulatory strategies to reduce exposure to endocrine-disrupting chemicals and protect female reproductive health.

PMID:41966417 | DOI:10.1016/j.reprotox.2026.109239

Environ Pollut. 2026 Apr 10;398:128082. doi: 10.1016/j.envpol.2026.128082. Online ahead of print.

ABSTRACT

Microplastics (MPs) are widespread environmental contaminants that have entered the human food chain, whose systemic health effects remain largely unknown. Using zebrafish as a vertebrate model, we investigated the mechanistic impacts of MPs on the liver-brain axis. After 18 days of exposure, zebrafish exhibited inhibited growth and neurobehavioral deficits, including reduced feeding, hyperactivity, spatial disorientation, and impaired sensorimotor responses. MPs accumulated in the brain, leading to structural damage, oxidative stress, and neurotransmitter depletion. Molecular docking revealed that MP monomers competitively bound to acetylcholinesterase (AChE), disrupting cholinergic signaling and inducing neuroexcitation. Simultaneously, MPs triggered hepatic inflammation, enzyme dysfunction, and lipid metabolic disturbances. Biochemical analysis showed elevated inflammatory markers (IL-1β, TNF-α, HSP90), compromised antioxidant defenses, increased transaminase leakage, and mitochondrial dysfunction. Untargeted metabolomics revealed hepatic metabolic reprogramming, with disrupted glycolysis, lipid turnover, and redox homeostasis. Pathway analysis implicated liver injury as a driver of neurotoxicity, potentially via altered metabolites and cytokines crossing the blood-brain barrier to influence neuroinflammatory and neuroendocrine responses. These findings highlight a mechanistic link between hepatic dysfunction and neural impairment, suggesting hepatic metabolic dysfunction as a potential systemic contributor to MP-induced neurotoxicity, and offering novel insights into the potential human health risks of MP exposure.

PMID:41966363 | DOI:10.1016/j.envpol.2026.128082

Aquat Toxicol. 2026 Apr 3;295:107818. doi: 10.1016/j.aquatox.2026.107818. Online ahead of print.

ABSTRACT

Microplastic (MP) contamination is a notable environmental challenge affecting marine ecosystems. However, its repercussions on the reproductive success of sea turtles remain inadequately elucidated. In this systematic review, we aggregated global data on the prevalence, characteristics, and biological ramifications of MPs within sea turtle nesting habitats and developmental stages. Information was compiled from studies conducted across principal nesting sites, including China, Malaysia, Mexico, Japan, and the Mediterranean region, based on the PRISMA guidelines. The findings revealed substantial spatial heterogeneity in MP concentrations, from 1513 particles/m² on the Qilianyu Islands to ˃12,000 items/kg of dry sand on Redang Island. Polyethylene (PE), polystyrene (PS), and polyethylene terephthalate (PET) were the predominant types of MPs, which primarily manifested in fiber and foam forms. Evidence indicates that MPs permeate the nesting substrate, including sediment layers corresponding to egg incubation depth, and accumulate within turtle eggs, yolks, and embryonic tissues. Phthalate esters (PAEs) and MP particles measuring ˂5 µm were identified in yolk and liver tissues, indicating maternal transfer and the potential for endocrine disruption. Sublethal effects included increased melanomacrophage activity in embryos, intestinal obstruction, and reduced body condition in post-hatchlings. Additionally, dark-hued MPs may increase nesting temperatures, thereby affecting sex ratios in temperature-dependent sex determination (TSD) frameworks. These findings suggest that persistent MP exposure may impair embryonic development, alter hatchling fitness, and potentially reduce long-term population recruitment and resilience. Mitigating microplastic pollution is essential for ensuring the reproductive viability, population resilience, and enduring conservation of sea turtle species.

PMID:41966798 | DOI:10.1016/j.aquatox.2026.107818

Environ Int. 2026 Apr 8;210:110247. doi: 10.1016/j.envint.2026.110247. Online ahead of print.

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) exposure may cause endocrine disruption. However, PFAS exposure and their potential associations with thyroid hormones remain unclear in coal mining areas.

OBJECTIVES: To characterize PFAS exposure profile and their associations among this population.

METHODS: Serum levels of PFASs and thyroid hormones were measured in 760 participants. Multiple linear regression and restricted cubic spline models assessed individual PFAS associations with thyroid hormones, while Bayesian kernel machine regression and quantile-based g-computation evaluated joint effects. Stratification and sensitivity analyses were conducted to verify the validity and robustness of results.

RESULTS: PFOA was extraordinarily high (median: 1623 μg/L), reaching 10-fold those of fluorochemical plant workers, and showed a positive correlation with a 0.057 increase in FT4 per ln-unit (95% CI: 0.006, 0.107). Emerging PFAS substitutes showed stronger, non-linear dose-response associations with thyroid hormones than legacy compounds. PFAS mixture exposure was inversely associated with FT3, TT4, TT4/FT3 and TT4/FT4 (β: -4.816 to -0.071, 95% CI: -6.708 to -0.121, -2.923 to -0.021), but positively with FT4/FT3 (β: 0.074, 95% CI: 0.021, 0.126). Age and BMI were important effect modifiers for associations between PFASs and thyroid hormones, with underweight and obese individuals being more susceptible.

CONCLUSIONS: PFAS exposure levels were extraordinarily high and significantly associated with thyroid hormones. Emerging substitutes showed stronger effects and complex bidirectional influences, and mixture exposure exerted the same effects. Age and BMI served as important effect modifiers. Notably high PFAS exposure and their strong links to thyroid hormone homeostasis in coal mining population warranted further validation.

PMID:41966766 | DOI:10.1016/j.envint.2026.110247

Mol Immunol. 2026 Apr 11;194:13-29. doi: 10.1016/j.molimm.2026.04.002. Online ahead of print.

ABSTRACT

OBJECTIVE: The relationship between periodontitis and diabetes is well-established, yet the underlying mechanisms are incompletely understood. This study aimed to investigate the role of Klebsiella pneumoniae (Kp94), isolated from the salivary microbiota of periodontitis patients, in exacerbating diabetes by disrupting intestinal immunity and metabolic homeostasis.

DESIGN: Following the induction of periodontitis by ligation and oral gavage of Kp94, the systemic metabolic status of the mice was assessed through the Disease Activity Index (DAI), intraperitoneal glucose tolerance test (IPGTT), and measurements of serum total cholesterol (TC) and glycated hemoglobin (HbA1c). To investigate the underlying mechanisms, transcriptomic analysis of intestinal tissues and 16S rRNA sequencing of intestinal contents were performed. Furthermore, intestinal immunity was evaluated by immunohistochemistry/immunofluorescence, and the proportion of ILC3s was analyzed by flow cytometry.

RESULTS: Kp94 induced gut microbiota dysbiosis and systemic glucose intolerance. Mechanistically, Kp94 suppressed the intestinal ILC3/IL-22 pathway, which impaired mucosal immunity by reducing antimicrobial peptide (BD3, LCN2) expression, disrupting the mucus barrier, and increasing intestinal permeability. Concomitantly, this suppression inhibited endocrine function, notably GLP-1 production. Crucially, IL-22 administration rescued these defects by alleviating endoplasmic reticulum stress, thereby restoring barrier and endocrine integrity, and improving metabolic parameters, including HbA1c.

CONCLUSION: Our findings suggest that the intestinal ILC3/IL-22 pathway may serve as a potential mechanistic link and therapeutic target for the metabolic and pancreatic damage associated with Kp94 in periodontitis-related diabetes.

PMID:41967182 | DOI:10.1016/j.molimm.2026.04.002

Aquat Toxicol. 2026 Apr 3;295:107818. doi: 10.1016/j.aquatox.2026.107818. Online ahead of print.

ABSTRACT

Microplastic (MP) contamination is a notable environmental challenge affecting marine ecosystems. However, its repercussions on the reproductive success of sea turtles remain inadequately elucidated. In this systematic review, we aggregated global data on the prevalence, characteristics, and biological ramifications of MPs within sea turtle nesting habitats and developmental stages. Information was compiled from studies conducted across principal nesting sites, including China, Malaysia, Mexico, Japan, and the Mediterranean region, based on the PRISMA guidelines. The findings revealed substantial spatial heterogeneity in MP concentrations, from 1513 particles/m² on the Qilianyu Islands to ˃12,000 items/kg of dry sand on Redang Island. Polyethylene (PE), polystyrene (PS), and polyethylene terephthalate (PET) were the predominant types of MPs, which primarily manifested in fiber and foam forms. Evidence indicates that MPs permeate the nesting substrate, including sediment layers corresponding to egg incubation depth, and accumulate within turtle eggs, yolks, and embryonic tissues. Phthalate esters (PAEs) and MP particles measuring ˂5 µm were identified in yolk and liver tissues, indicating maternal transfer and the potential for endocrine disruption. Sublethal effects included increased melanomacrophage activity in embryos, intestinal obstruction, and reduced body condition in post-hatchlings. Additionally, dark-hued MPs may increase nesting temperatures, thereby affecting sex ratios in temperature-dependent sex determination (TSD) frameworks. These findings suggest that persistent MP exposure may impair embryonic development, alter hatchling fitness, and potentially reduce long-term population recruitment and resilience. Mitigating microplastic pollution is essential for ensuring the reproductive viability, population resilience, and enduring conservation of sea turtle species.

PMID:41966798 | DOI:10.1016/j.aquatox.2026.107818

Environ Int. 2026 Apr 8;210:110247. doi: 10.1016/j.envint.2026.110247. Online ahead of print.

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) exposure may cause endocrine disruption. However, PFAS exposure and their potential associations with thyroid hormones remain unclear in coal mining areas.

OBJECTIVES: To characterize PFAS exposure profile and their associations among this population.

METHODS: Serum levels of PFASs and thyroid hormones were measured in 760 participants. Multiple linear regression and restricted cubic spline models assessed individual PFAS associations with thyroid hormones, while Bayesian kernel machine regression and quantile-based g-computation evaluated joint effects. Stratification and sensitivity analyses were conducted to verify the validity and robustness of results.

RESULTS: PFOA was extraordinarily high (median: 1623 μg/L), reaching 10-fold those of fluorochemical plant workers, and showed a positive correlation with a 0.057 increase in FT4 per ln-unit (95% CI: 0.006, 0.107). Emerging PFAS substitutes showed stronger, non-linear dose-response associations with thyroid hormones than legacy compounds. PFAS mixture exposure was inversely associated with FT3, TT4, TT4/FT3 and TT4/FT4 (β: -4.816 to -0.071, 95% CI: -6.708 to -0.121, -2.923 to -0.021), but positively with FT4/FT3 (β: 0.074, 95% CI: 0.021, 0.126). Age and BMI were important effect modifiers for associations between PFASs and thyroid hormones, with underweight and obese individuals being more susceptible.

CONCLUSIONS: PFAS exposure levels were extraordinarily high and significantly associated with thyroid hormones. Emerging substitutes showed stronger effects and complex bidirectional influences, and mixture exposure exerted the same effects. Age and BMI served as important effect modifiers. Notably high PFAS exposure and their strong links to thyroid hormone homeostasis in coal mining population warranted further validation.

PMID:41966766 | DOI:10.1016/j.envint.2026.110247

Comp Biochem Physiol C Toxicol Pharmacol. 2026 Apr 9:110543. doi: 10.1016/j.cbpc.2026.110543. Online ahead of print.

ABSTRACT

Endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), are prevalent pollutants in aquatic ecosystems and may present developmental risks to exposed organisms, especially in viviparous matrotrophic organisms, where the physiological processes that enable mothers to supply nutrients to embryos during gestation (matrotrophy) also allow EDCs to reach the developing offspring. In this study we examined the impact of prenatal BPA exposure in the live-bearing fish, Heterandria formosa. Gravid females were exposed to 200 μg/L BPA dissolved in ethanol, water control, or ethanol solvent to measure direct maternal effects via changes in cortisol and indirect effects of exposure on offspring cortisol. Additionally, we evaluated offspring behavior and cognitive performance along with gene expression after the exposure ceased. We predicted indirect effects of exposure to BPA on offspring, but contrary to our predictions, prenatal BPA exposure did not significantly affect offspring cognition, behavior, cortisol, or overall gene expression. However, in exploratory comparisons of solving status we found evidence that BPA and ethanol dampened the gene expression differences between solvers and non-solvers that were present under baseline (water). These results suggest that while BPA alters gene expression patterns under certain conditions, behavioral and cognitive traits, such as problem-solving and inhibitory control, are likely regulated by factors beyond gene expression alone, including physiological processes like cortisol regulation and potentially gene networks. Moreover, our results suggest this species of live-bearing fish provides protection for offspring from long-term effects of high prenatal BPA exposure, although the possibility of epigenetic or delayed multigenerational effects cannot be ruled out.

PMID:41966287 | DOI:10.1016/j.cbpc.2026.110543

Neurotoxicology. 2026 Apr 9:103450. doi: 10.1016/j.neuro.2026.103450. Online ahead of print.

ABSTRACT

Phthalates are ubiquitous environmental contaminants and endocrine-disrupting chemicals used as plasticizers in consumer products, medical devices, and industrial materials. Evidence from in vitro experiments, animal models, and epidemiological studies suggests that phthalate exposure particularly to di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and benzyl butyl phthalate (BBP), may induce neurotoxicity through multiple interconnected mechanisms. The developing brain is especially vulnerable, with prenatal and early-life exposures linked to cognitive deficits, behavioral abnormalities, and neurodevelopmental disorders. Conventional therapeutic options remain limited, highlighting the need for effective neuroprotective strategies. Natural bioactive compounds such as polyphenols, flavonoids, carotenoids, and other phytochemicals have been investigated as potential neuroprotective candidates in preclinical models owing to their multi-target mechanisms (e.g., antioxidant, anti-inflammatory, and neurotrophic actions), potent antioxidant capacity, and regulation of cellular signaling pathways. Preclinical studies demonstrate that lycopene, ferulic acid, coenzyme Q10, omega-3 fatty acids, vanillic acid, and Moringa oleifera extracts attenuate phthalate-induced neurotoxicity by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, suppressing nuclear factor-kappa B (NF-κB)-mediated inflammation, modulating MAPK/ERK and PI3K/Akt signaling, and restoring brain-derived neurotrophic factor (BDNF)/TrkB support. Despite these promising findings, challenges persist, including poor bioavailability, lack of standardized dosing, and limited human clinical trials. A structured review of experimental and epidemiological studies was conducted using predefined inclusion criteria. This review integrates evidence across in vitro, in vivo, and human studies to identify key mechanisms of phthalate-induced neurotoxicity, including oxidative stress, neuroinflammation, endocrine disruption, epigenetic dysregulation, and impaired neuroplasticity, and evaluates pathway-specific neuroprotective actions of bioactive compounds while highlighting critical translational gaps.

PMID:41966340 | DOI:10.1016/j.neuro.2026.103450

Ecotoxicol Environ Saf. 2026 Apr 11;316:120124. doi: 10.1016/j.ecoenv.2026.120124. Online ahead of print.

ABSTRACT

This study aimed to investigate the association between per- and polyfluoroalkyl substances (PFAS) mixture exposure and hypertension risk, and to assess the mediating role of estradiol. We investigated these questions in 5175 adults from the U.S. National Health and Nutrition Examination Survey (NHANES 2011-2020). Serum concentrations of six PFAS and estradiol were quantified. Using weighted quantile sum (WQS) regression, we evaluated the joint effect of the PFAS mixture on hypertension (2017 ACC/AHA criteria). Restricted cubic splines (RCS) characterized exposure-response shapes, and causal mediation analysis tested estradiol as a potential mechanistic pathway. After full adjustment, perfluorononanoic acid (PFNA) exhibited the strongest association with hypertension (odds ratio per ln-unit increase, 1.16; 95% CI, 1.06-1.27). WQS regression identified PFNA as the primary driver of the mixture effect (weighted contribution, 37.5%). Crucially, estradiol significantly mediated 4.68% of the association between PFNA and hypertension, and 4.22% for perfluorooctanoic acid (PFOA). Sex-stratified analyses revealed that the associations of PFNA and PFOA with hypertension were significant only in females. All analyses accounted for the complex survey design and were adjusted for sociodemographic, lifestyle, and clinical factors. Our integrated analytical approach identifies PFNA, a long-chain PFAS, as a key driver of hypertension risk within environmental PFAS mixtures. The finding that estradiol reduction mediates this association provides novel evidence for an endocrine-disruption mechanism and explains observed female-specific susceptibility. These results highlight the importance of compound-specific prioritization and sex-aware frameworks in environmental risk assessment.

PMID:41967265 | DOI:10.1016/j.ecoenv.2026.120124

ALTEX. 2026 Apr 9. doi: 10.14573/altex.2512011. Online ahead of print.

ABSTRACT

Bisphenol A is a high production volume chemical used extensively in the manufacture of polycarbonate plastics, epoxy resins, and thermal printer paper with a high potential for occupational and post-production dermal exposure. Bisphenol A-containing plastics were commonly used in food packaging resulting in significant public exposure through leaching into foodstuff. The public is also at risk of dermal exposure due to environmental contamination. Due to public health concerns regarding the potential for endocrine disrupting effects, efforts have been applied to replace bisphenol A with safer alternatives. Bisphenol A has been shown to cause skin sensitization in humans; however, there is a paucity of information available on the sensitizing potential of structural analogues which are increasingly being employed as substitutes. We utilized new approach methodologies (NAMs) addressing key events 1-3 of the adverse outcome pathway for skin sensitization to address the potential of bisphenol A substitutes to induce dermal sensitization. Defined approaches (DA) were applied to further classify and categorize potency according to OECD TG 497. The NAMs and DAs confirmed that bisphenol A was a skin sensitizer in potency category UN GHS 1B. Bisphenol B, AP, and E were also classified as UN GHS 1B sensitizers, and bisphenol AF as UN GHS 1A/1B depending on DA, while 2,4-bisphenol S and F were borderline sensitizers, and bisphenol S was classified as a non-sensitizer. These data provide evidence of skin sensitization hazard for the bisphenol structural analogues tested, except for bisphenol S, suggesting that they present risks for dermal allergy.

PMID:41964411 | DOI:10.14573/altex.2512011

Kaohsiung J Med Sci. 2026 Apr 11:e70208. doi: 10.1002/kjm2.70208. Online ahead of print.

ABSTRACT

Parabens (parahydroxybenzoates), which are frequently used as preservatives in pharmaceuticals, foodstuffs, and personal care products, have recently attracted considerable attention due to their adverse health effects and endocrine-disrupting properties. This study aimed to determine the background urinary concentrations of parabens in a representative sample of the general population in Taiwan. A total of 1967 participants were enrolled in this cross-sectional study. The subjects were recruited from the Taiwan Environmental Survey for Toxicants (2013-2016). Urine samples were collected from participants, and questionnaires were administered. Urinary concentrations of parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), were quantified through ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Overall, 95th percentile reference values (RV95s) were used to establish the background concentrations of these parabens. The highest geometric mean concentration was obtained for MeP (357 μg/L), followed by PrP (89.3 μg/L), EtP (34.2 μg/L), and BuP (5.31 μg/L). Urinary concentrations of these parabens were higher in adults than in minors. The RV95s of paraben were 954, 101, 219, and 14.2 μg/L for MeP, EtP, PrP, and BuP, respectively. Of the 1967 participants, 55.4% had a HI value that exceeded the threshold of 1. This finding indicates a potential concern under conservative screening assumptions, rather than definitive evidence of adverse health risk. PrP was identified as the primary determinant of HI, accounting for 71.4% of the observed effect. The RV95s for the urinary concentrations of particular parabens are significantly higher in Taiwan than in other countries. Moreover, a notable correlation was observed between personal care product use and the urinary paraben concentrations. Further evaluation of the health implications of paraben exposure among the Taiwanese population is warranted.

PMID:41964412 | DOI:10.1002/kjm2.70208

Inorg Chem. 2026 Apr 11. doi: 10.1021/acs.inorgchem.6c00500. Online ahead of print.

ABSTRACT

The remediation of endocrine-disrupting compounds, such as bisphenol A (BPA), demands advanced oxidation technologies capable of ultrafast and selective pollutant destruction. Herein, we report the rational design and synthesis of NiZn₂O₄ nanoparticles embedded in carbon nanocages (NiZn₂O₄@CNs) derived from bimetallic zeolitic imidazolate frameworks (ZIF), for efficient BPA degradation. The unique hollow nanocage architecture, featuring a well-defined mesoporous structure inherited from the MOF precursor, facilitates the mass transfer of the reactants and products. More importantly, the constructed spinel-type NiZn₂O₄ active sites, in conjunction with the conductive carbon matrix, endow the catalyst with an exceptional electron shuttle effect, which significantly accelerates the electron transfer from BPA to PMS. Consequently, the optimized NiZn₂O₄@CNs catalysts achieve an outstanding BPA degradation efficiency of 99% within only 5 min, reaching the high kinetic rate of 0.5382 min^-1. Quenching experiments and electron paramagnetic resonance tests reveal that singlet oxygen (¹O₂) is the dominant reactive oxygen species in the catalytic system. The catalyst further demonstrates exceptional stability, reusability, and broad applicability against diverse phenolic contaminants. This work provides a foundational blueprint for designing MOF-derived electron-shuttle catalysts, advancing the frontier of pollutant-specific advanced oxidation processes.

PMID:41964576 | DOI:10.1021/acs.inorgchem.6c00500

Sci Rep. 2026 Apr 11. doi: 10.1038/s41598-026-44827-4. Online ahead of print.

ABSTRACT

Glyphosate is the most extensively applied systemic herbicide worldwide, yet its safety remains under scrutiny, with ongoing investigations into potential carcinogenicity. Epidemiological studies associate chronic glyphosate exposure with elevated risks of non-Hodgkin lymphoma and possible endocrine disruption, emphasizing the need for sensitive detection methods. Here, we report a handheld enzymatic biosensor, GlyphoSense Chip, for direct, rapid detection of underivatized glyphosate in drinking water. The device integrates a photodiode-based CMOS chip with an engineered glyphosate N-acetyltransferase and a colorimetric reaction, achieving a sensitivity of 38 µV·mL µg^-1·s^-1 and quantification within one minute. Biosensor response was linear over 0.016-12.5 µg mL^-1 (R² = 0.993) with a detection limit of 0.028 µg mL^-1. Recovery analysis in fortified tap water yielded relative standard errors of 1.2-5.8%, and results were statistically indistinguishable from quantitative mass spectrometry (p > 0.05). This work establishes a robust, field-deployable platform for glyphosate monitoring in water resource safety applications.

PMID:41965777 | DOI:10.1038/s41598-026-44827-4

Can J Cardiol. 2026 Apr 8:S0828-282X(26)00300-4. doi: 10.1016/j.cjca.2026.03.050. Online ahead of print.

ABSTRACT

Exposure to environmental pollutants and toxicants is increasingly recognized as a major determinant of cardiovascular disease (CVD). Beyond direct toxic effects, these agents profoundly alter immune homeostasis, thereby contributing to endothelial dysfunction, atherogenesis, arrhythmogenesis, and impaired myocardial repair. Among emerging pollutants, micro- and nanoplastics (MNPs) have recently gained attention due to their ubiquity and potential cardiovascular impact. This narrative review synthesizes mechanistic, translational, and clinical evidence on pollutant-induced cardiovascular injury mediated by immune dysfunction. We integrate data from experimental models, human tissue studies, and clinical observations to delineate shared and pollutant-specific immunoinflammatory pathways, with a particular focus on MNPs. Environmental toxicants, including particulate matter, heavy metals, endocrine disruptors, and MNPs, promote chronic innate immune activation, mitochondrial stress responses, NLRP3 inflammasome signaling, and maladaptive epigenetic reprogramming of myeloid cells. MNPs have been detected in human cardiovascular tissues and are associated with adverse cardiovascular events. Experimental evidence indicates that MNPs accumulate within vascular and cardiac compartments, disrupt endothelial barrier integrity, enhance macrophage pro-inflammatory polarization, and amplify oxidative and nitrosative stress. These converging mechanisms foster plaque vulnerability, microvascular instability, and increased susceptibility to ischemic and arrhythmic complications. Environmental cardiopathogenesis represents a rapidly expanding frontier in cardioimmunology. Elucidating the immune-mediated mechanisms linking pollutant exposure-particularly MNPs-to cardiovascular injury may improve risk stratification and inform targeted preventive and therapeutic strategies in increasingly polluted environments.

PMID:41962839 | DOI:10.1016/j.cjca.2026.03.050

J Expo Sci Environ Epidemiol. 2026 Apr 10. doi: 10.1038/s41370-026-00868-5. Online ahead of print.

ABSTRACT

BACKGROUND: Bisphenol S (BPS) is a chemical analogue of Bisphenol A (BPA) used in the production of hard plastics, textiles, and thermal papers. As the use of BPA has declined, BPS human exposure has increased and is now widespread. BPS has endocrine-disrupting properties and growing evidence indicates BPS negatively impacts female reproductive health.

OBJECTIVE: We conducted a scoping review of primary research articles related to BPS exposure and female reproductive toxicity in humans.

METHODS: We searched five biomedical databases through January 2025 for studies that assessed the effects of BPS exposure on outcomes related to female reproduction in humans. Included studies used a cohort, case-control, or cross-sectional study design, measured BPS in individuals, presented original data analyses, and adjusted for confounding variables. We tabulated study characteristics and key findings of the included studies.

RESULTS: The literature search and screening yielded thirty-four studies for inclusion. Across studies, the LOD for BPS varied widely, from 0.002 to 0.20 ng/mL, and so did the proportion of samples with detectable BPS, from 14.8% to 100%. BPS was associated with greater risk of polycystic ovarian syndrome in two studies and gestational diabetes mellitus or related biomarkers in three studies. BPS was also associated with changes in thyroid hormones, reproductive hormones, and pubertal timing, though the directions of effects for these outcomes were mixed. BPS was not associated with endometriosis, gestational hypertension, or infertility.

SIGNIFICANCE: There is evidence from human studies that BPS exposure can cause some adverse female reproduction outcomes, though data were limited in number of studies per outcome, variable limits of BPS detection, and differences in exposure to BPS across samples. Despite limitations, epidemiologic data, considered along with in vitro and animal data, is important in identifying BPS as a hazard to female reproduction.

IMPACT: Human exposure to BPS is increasing. The findings of this review of 34 epidemiologic studies suggests a link between BPS exposure and some adverse female reproductive health outcomes. This review also highlights data gaps in variable limits of BPS detection, differences in exposure, and the limited number of studies for specific outcomes. In addition to epidemiological evidence, in vitro and animal data show sufficient evidence to support BPS as a female reproductive.

PMID:41963602 | DOI:10.1038/s41370-026-00868-5

Can J Cardiol. 2026 Apr 8:S0828-282X(26)00300-4. doi: 10.1016/j.cjca.2026.03.050. Online ahead of print.

ABSTRACT

Exposure to environmental pollutants and toxicants is increasingly recognized as a major determinant of cardiovascular disease (CVD). Beyond direct toxic effects, these agents profoundly alter immune homeostasis, thereby contributing to endothelial dysfunction, atherogenesis, arrhythmogenesis, and impaired myocardial repair. Among emerging pollutants, micro- and nanoplastics (MNPs) have recently gained attention due to their ubiquity and potential cardiovascular impact. This narrative review synthesizes mechanistic, translational, and clinical evidence on pollutant-induced cardiovascular injury mediated by immune dysfunction. We integrate data from experimental models, human tissue studies, and clinical observations to delineate shared and pollutant-specific immunoinflammatory pathways, with a particular focus on MNPs. Environmental toxicants, including particulate matter, heavy metals, endocrine disruptors, and MNPs, promote chronic innate immune activation, mitochondrial stress responses, NLRP3 inflammasome signaling, and maladaptive epigenetic reprogramming of myeloid cells. MNPs have been detected in human cardiovascular tissues and are associated with adverse cardiovascular events. Experimental evidence indicates that MNPs accumulate within vascular and cardiac compartments, disrupt endothelial barrier integrity, enhance macrophage pro-inflammatory polarization, and amplify oxidative and nitrosative stress. These converging mechanisms foster plaque vulnerability, microvascular instability, and increased susceptibility to ischemic and arrhythmic complications. Environmental cardiopathogenesis represents a rapidly expanding frontier in cardioimmunology. Elucidating the immune-mediated mechanisms linking pollutant exposure-particularly MNPs-to cardiovascular injury may improve risk stratification and inform targeted preventive and therapeutic strategies in increasingly polluted environments.

PMID:41962839 | DOI:10.1016/j.cjca.2026.03.050

Food Chem Toxicol. 2026 Apr 8:116076. doi: 10.1016/j.fct.2026.116076. Online ahead of print.

ABSTRACT

EDCs such as pesticides and biocides may enter the food supply and be ingested by humans. Once absorbed, these substances are metabolized in the liver and subsequently distributed systemically. However, conventional in vitro assays assess only parent compounds, failing to consider the biological activity of metabolites formed through hepatic metabolism. This study integrated the S9 fraction, an enzyme extract from the liver tissue, into the OECD TG 458 assay to analyze Phases I and II metabolic processes. We introduced the non-metabolizable compound STZ as a new positive control, set a 6 h metabolism based on BPA and bicalutamide metabolism, and established metabolic activity criteria using STZ variability. Using this improved method, we evaluated AR activity and metabolic changes of 57 biocides regulated in Korea. The parent and metabolite forms of all biocides were negative for AR agonist activity. In the AR antagonist assays, 24 parent compounds were positive, 7 lost activity after metabolism, and 17 retained activity. This study demonstrated that incorporating hepatic metabolism into in vitro assays can classify EDCs whose toxicity is reduced through metabolism from those that retain endocrine-disrupting potential. Therefore, this approach may improve the identification of EDCs that pose a greater risk to human health.

PMID:41962648 | DOI:10.1016/j.fct.2026.116076

J Clin Endocrinol Metab. 2026 Apr 8:dgag149. doi: 10.1210/clinem/dgag149. Online ahead of print.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) pose a significant global health risk by interfering with hormonal balance. The thyroid is particularly suitable for studying endocrine disruption due to its crucial role in development, metabolism, and cognitive function, alongside established molecular targets and regulatory frameworks. This review summarizes current knowledge on thyroid-disrupting chemicals (TDs), focusing on mechanistic pathways acting at both intra-thyroidal and extra-thyroidal levels. Particular attention is given to molecular initiating events, such as interference with iodide uptake, thyroperoxidase activity, thyroglobulin processing, and thyroid hormone signaling, and to their integration within the Adverse Outcome Pathway (AOP) framework. In addition, the review discusses methodological strategies for assessing thyroid disruption, spanning in silico, in vitro, in vivo, and human epidemiological approaches. Finally, emerging challenges related to real-world exposure to chemical mixtures are addressed, highlighting the need for AOP-informed, mixture-based strategies to improve risk assessment and regulatory decision-making.

PMID:41961635 | DOI:10.1210/clinem/dgag149

J Endocr Soc. 2026 Mar 16;10(4):bvag050. doi: 10.1210/jendso/bvag050. eCollection 2026 Apr.

ABSTRACT

We investigated how developmental exposure to the commercial flame retardant (FR) mixture Firemaster 550 (FM 550) affects estrogen receptor alpha (ERα) expression in key brain regions related to sociosexual behavior. We used prairie voles, a socially monogamous, biparental rodent species of high translational human relevance. This study used adult siblings from a prior behavioral study showing developmental FM 550 exposure impaired a range of socioemotional behaviors in adults including loss of partner preference in males. Dams were exposed to FM 550 (500, 1000, or 2000 µg/day) via subcutaneous injections throughout gestation, and pups were directly exposed from birth to weaning. ERα immunoreactive (ERα-ir) neuron numbers and mRNA expression levels were quantified in subregions of the social brain neural network (SBNN). As anticipated, FM 550 impacts were sex-, dose-, and region-specific, with FM 550 tending to increase ERα-ir cell numbers in the anterior hypothalamus regardless of sex, but decrease them in the female mediobasal hypothalamus, amygdala, and extended amygdala. These studies demonstrate that developmental FR exposure impacts adult SBNN ERα availability and provide support that disrupted ERα action in the SBNN may be a mechanism underlying disruption of socioemotional behavior, energy balance, and related neuroendocrine physiology. Impacted ERα neuronal populations are also influenced by other receptors, neuropeptides, neurosteroids, and signaling molecules to govern prosocial behaviors, which is the ongoing direction of this work. Collectively, these data add to growing evidence that FM 550 FRs are neuroendocrine disruptors that can induce persistent impacts across developing socioemotional pathways and systems.

PMID:41958868 | PMC:PMC13058731 | DOI:10.1210/jendso/bvag050

Toxicol Ind Health. 2026 Apr 10:7482337261441688. doi: 10.1177/07482337261441688. Online ahead of print.

ABSTRACT

Endocrine-disrupting chemicals (EDCs), including heavy metals such as lead (Pb), interfere with hormonal homeostasis, particularly in the hypothalamic-pituitary-gonadal (HPG) axis. Occupational lead exposure is linked to male reproductive dysfunction and cardiovascular risk via oxidative stress and endothelial impairment. This study investigated the effects of chronic lead exposure on testosterone levels and the L-arginine-nitric oxide (NO) pathway, a key regulator of endothelial function. This case-control study compared 120 male workers with occupational lead exposure (in battery manufacturing and foundries) to 120 unexposed controls. Blood lead levels (BLLs) were quantified via inductively coupled plasma mass spectrometry (ICP-MS), while testosterone (total/free) and methylated arginine metabolites; asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and citrulline were analyzed using LC-MS/MS. Statistical analyses included t-tests and Pearson correlations to assess associations. Lead-exposed workers had significantly higher BLLs (31.76 ± 13.31 vs 1.72 ± 0.87 μg/dL), lower total testosterone (388.23 ± 71.78 vs 477.36 ± 104.21 ng/dL), and reduced arginine/ADMA ratios (432.48 ± 191.27 vs 544.33 ± 187.19), indicating endothelial dysfunction. Strong inverse correlations were observed between exposure duration, classified as 6 months to 1 year, 1 to 5 years, and >5 years, to evaluate its association with BLL, testosterone levels, and arginine metabolism markers. This study demonstrated that chronic occupational lead exposure significantly disrupted testosterone secretion and impaired the L-arginine-NO pathway, highlighting its dual threat to reproductive and cardiovascular health. The robust inverse correlations between BLL, testosterone, and arginine/ADMA ratios underscore the endocrine-disrupting and endothelial-damaging effects of lead. These findings support the routine biomonitoring of BLL, testosterone, and methylated arginine metabolites in high-risk occupations to enable early intervention and mitigate long-term health risks.

PMID:41961018 | DOI:10.1177/07482337261441688

Front Physiol. 2026 Mar 25;17:1747210. doi: 10.3389/fphys.2026.1747210. eCollection 2026.

ABSTRACT

Multiple point and nonpoint sources add complex mixtures of pollutants that may pose detrimental impacts on freshwater fish. These pollutants include metallic and nonmetallic inorganic ions and an array of organic compounds. Climate-related scenarios and a mixture of contaminants entering riverine ecosystems have impacted many endemic freshwater fish species in Sri Lanka. The present research aims to identify morphological, physiological, and behavioral changes upon exposure to xenobiotics and to predict the influence of climate on these fishes. We discussed the biomarker responses of feral fish, combined with their physicochemical characterization. Moreover, the discussion emphasized empirical evidence from controlled laboratory experiments. Together, these elements were used to interpret the possible future impacts of climate change on the fish in lotic ecosystems. The effects of nanoparticles, microplastics, pharmaceuticals, and endocrine disruptors, and their interplay with climate-related physicochemical variation, have been identified as a research gap. The primary research directions for the future include establishing multi-stressor experimental frameworks that integrate a mixture of xenobiotic exposures of indigenous fishes. The development of standardized biological monitoring protocols that simulate real-world conditions in lotic ecosystems is crucial. Introduction of scientific, evidence-based, robust, and urgent legislative reforms to regulate cumulative pollution may provide a strong legal framework to prevent devastating impacts on freshwater fishes in lotic ecosystems in Sri Lanka.

PMID:41958527 | PMC:PMC13056829 | DOI:10.3389/fphys.2026.1747210

bioRxiv [Preprint]. 2026 Mar 9:2026.03.06.709997. doi: 10.64898/2026.03.06.709997.

ABSTRACT

Alcohol is an ancient and enduring component of the human diet, yet it is a dose-dependent cytotoxin and teratogen, raising the possibility that endogenous, state-dependent mechanisms constrain intake. Growth differentiation factor 15 (GDF15) is an endocrine hormone that rises during pregnancy-predominantly via secretion from blastocyst-derived placental trophoblasts into the maternal circulation-and is also induced in other tissues, particularly hepatocytes, by toxins and cellular stress. However, its function in humans remains unclear. Here, we show that circulating GDF15 levels are elevated 5-fold in individuals with alcohol dependence, identify a rare loss-of-function variant in the GDF15 receptor gene GFRAL associated with approximately 2.6 additional UK alcohol units (∼21 g ethanol) per week, and demonstrate that recombinant GDF15 reduces alcohol drinking in mice. Collectively, these findings support a model in which GDF15 acts as an endocrine signal induced by chronic alcohol exposure-and potentially during pregnancy-to limit alcohol intake in humans.

HIGHLIGHTS: GDF15 is markedly elevated in humans with alcohol dependenceA truncating GFRAL variant associates with higher alcohol intake in UK BiobankGFRAL frameshift disrupts GDF15-RET signaling in vitroRecombinant GDF15 suppresses voluntary alcohol intake in mice.

PMID:41959486 | PMC:PMC13060954 | DOI:10.64898/2026.03.06.709997

bioRxiv [Preprint]. 2026 Mar 14:2026.03.11.711132. doi: 10.64898/2026.03.11.711132.

ABSTRACT

INTRODUCTION: The major histocompatibility complex class II (MHC-II) pathway is central to adaptive immunity and immune tolerance, and age-related erosion of these mechanisms is increasingly recognized as a driver of chronic neuroinflammation. The HLA-DRB1*15:01 allele-the strongest genetic risk factor for multiple sclerosis in Caucasians-has been implicated in shaping pathogenic CD4⁺ T-cell responses and broader neuroimmune vulnerability, yet how this allele modulates age- and sex-dependent neuroimmune processes within the central nervous system (CNS) remains poorly defined.

METHODS: We investigated the impact of HLA-DRB1*15:01 expression using a humanized mouse model (HLA mice) and wild-type (WT) controls. Male and female mice were analyzed at 6, 9, and 15 months of age, with endocrine stratification in females. Behavioral testing, flow cytometry, immunofluorescence, and multiplex cytokine analyses were used to assess cognitive performance, glial activation and oxidative stress, astrocyte-microglia IL-3/IL-3R signaling, endothelial activation, selective immune cell accumulation at CNS borders, tissue organization, and hippocampal cytokine profiles.

RESULTS: HLA mice developed age- and sex-dependent cognitive impairment, most pronounced in aged females. HLA-DRB1*15:01 expression promoted progressive microglial activation, characterized by increased CD14 and CD68 expression, elevated mitochondrial oxidative stress, altered astrocyte phenotypes, and enhanced IL-3/IL-3R signaling. Hippocampal axonal and myelin organization was disrupted in aged HLA mice, and this disruption was spatially associated with increased microglial presence. At CNS interfaces, HLA mice exhibited selective immune remodeling, including increased accumulation of CD4⁺ T cells and NK1.1⁺CD3⁺ natural killer T (NKT) cells, particularly in females, accompanied by endothelial activation, as evidenced by elevated ICAM-1 and E-selectin expression. Hippocampal cytokine profiling revealed selective, sex-biased alterations, including increased IL-12p70 and reduced IL-10 and IL-2, without broad induction of classical inflammatory cytokines.

CONCLUSION: Together, these findings demonstrate that HLA-DRB1*15:01 drives a coordinated, age- and sex-dependent neuroinflammatory program linking behavioral dysfunction, glial activation and oxidative stress, selective immune cell recruitment, endothelial activation, tissue remodeling, and targeted cytokine imbalance. This integrated phenotype provides mechanistic insight into how this major MS risk allele confers vulnerability to chronic neuroinflammation during aging, with heightened impact in females.

PMID:41959035 | PMC:PMC13061024 | DOI:10.64898/2026.03.11.711132

Front Public Health. 2026 Mar 25;14:1755497. doi: 10.3389/fpubh.2026.1755497. eCollection 2026.

ABSTRACT

Microplastics (MPs), as emerging environmental pollutants, found from the deepest oceans to the highest mountains, and crucially, within the human body, have attracted increasing attention due to their widespread presence and potential health impacts. This review addresses the multifaceted influence of MP exposure on endocrine regulation, gut microecology, the potential transgenerational effects, and child growth and development. Firstly, the sources and environmental distribution characteristics of MPs were outlined, their persistence and bioaccumulation potential were highlighted. How MPs act as carriers of endocrine-disrupting chemicals, interfering with hormonal systems and potentially disrupting children's physiological development was elucidated subsequently. Special emphasis is placed on the mechanisms by which MPs alter gut microbial communities, leading to dysbiosis that may compromise immune function and metabolic processes in children. By synthesizing recent advances in toxicology, microbiology, and pediatric research, present review amalgamates insights from contemporary studies, elaborates the comprehensive health risks posed by MP exposure during critical developmental periods, underscoring the urgent need for targeted preventive and regulatory measures to mitigate MP-related health hazards and promote child health. We aim to provide a scientific foundation for future research directions of MPs exposure and the development of effective intervention strategies.

PMID:41960410 | PMC:PMC13057501 | DOI:10.3389/fpubh.2026.1755497

Front Toxicol. 2026 Mar 26;8:1768236. doi: 10.3389/ftox.2026.1768236. eCollection 2026.

ABSTRACT

Recent reports from worldwide reveal that micro/nanoplastics (MNPs) are pervasive pollutants affecting all ecosystems and a wide range of organisms, including animals, plants, fish, humans, and microorganisms. MNPs have been detected in food items, mother milk, vegetables, and other consumable products, indicating their potential to impact organisms across all life stages. These particles can enter the body through inhalation, ingestion, and dermal contact. Due to their small size, micro/nanoplastics can be readily absorbed by animals and plants, leading to adverse effects on human health and ecological integrity. The present review addresses recent concerns related to MNPs pollution in aquatic animals and crops, with a particular focus on fish and rice. Exposure to MNPs has been reported to impair fish growth performance, immune responses, antioxidant status, digestive functions, reproduction, transgenerational effects, endocrine regulation, vitellogenin induction, neurotransmitter activity, and blood biochemical profiles. Similarly, MNPs adversely affect rice production by influencing various stages of the cropping system, including seed germination, vegetative growth, root and shoot development, tillering, and grain yield. Notably, both fish and rice are staple food sources for humans, highlighting the significance of this issue for food safety and public health. This review emphasizes the urgent need for comprehensive studies on the impacts of micro/nanoplastics on aquatic animals and major food crops. It integrates systematic knowledge on the effects of MNPs on fish growth patterns, immunity, endocrine disruption, reproduction, and key physiological indices, as well as on rice growth and productivity. The synthesized information will be highly valuable for policymakers, government agencies, pollution control authorities, and other stakeholders in policy formulation and decision-making processes.

PMID:41960282 | PMC:PMC13061387 | DOI:10.3389/ftox.2026.1768236

Bioinformation. 2026 Jan 31;22(1):56-60. doi: 10.6026/973206300220056. eCollection 2026.

ABSTRACT

The impact of chronic stress on endocrine function, particularly its effects on cortisol, thyroid hormones, and sex hormones is of interest. The study employed a cross-sectional design, involving 120 participants (aged 18-60) exposed to chronic stress for 6 months or longer. Elevated cortisol levels and disruptions in thyroid and reproductive hormones were observed, particularly in those experiencing high stress. Data show the potential of biomarkers like thyroid-stimulating hormone (TSH) for monitoring stress-related endocrine dysfunctions. Thus, we show the significant role of chronic stress in hormone dysregulation and its associated health risks. The study offers insights into early detection and therapeutic strategies for stress-related health issues.

PMID:41960455 | PMC:PMC13058347 | DOI:10.6026/973206300220056

Front Physiol. 2026 Mar 25;17:1747210. doi: 10.3389/fphys.2026.1747210. eCollection 2026.

ABSTRACT

Multiple point and nonpoint sources add complex mixtures of pollutants that may pose detrimental impacts on freshwater fish. These pollutants include metallic and nonmetallic inorganic ions and an array of organic compounds. Climate-related scenarios and a mixture of contaminants entering riverine ecosystems have impacted many endemic freshwater fish species in Sri Lanka. The present research aims to identify morphological, physiological, and behavioral changes upon exposure to xenobiotics and to predict the influence of climate on these fishes. We discussed the biomarker responses of feral fish, combined with their physicochemical characterization. Moreover, the discussion emphasized empirical evidence from controlled laboratory experiments. Together, these elements were used to interpret the possible future impacts of climate change on the fish in lotic ecosystems. The effects of nanoparticles, microplastics, pharmaceuticals, and endocrine disruptors, and their interplay with climate-related physicochemical variation, have been identified as a research gap. The primary research directions for the future include establishing multi-stressor experimental frameworks that integrate a mixture of xenobiotic exposures of indigenous fishes. The development of standardized biological monitoring protocols that simulate real-world conditions in lotic ecosystems is crucial. Introduction of scientific, evidence-based, robust, and urgent legislative reforms to regulate cumulative pollution may provide a strong legal framework to prevent devastating impacts on freshwater fishes in lotic ecosystems in Sri Lanka.

PMID:41958527 | PMC:PMC13056829 | DOI:10.3389/fphys.2026.1747210

Front Public Health. 2026 Mar 25;14:1755497. doi: 10.3389/fpubh.2026.1755497. eCollection 2026.

ABSTRACT

Microplastics (MPs), as emerging environmental pollutants, found from the deepest oceans to the highest mountains, and crucially, within the human body, have attracted increasing attention due to their widespread presence and potential health impacts. This review addresses the multifaceted influence of MP exposure on endocrine regulation, gut microecology, the potential transgenerational effects, and child growth and development. Firstly, the sources and environmental distribution characteristics of MPs were outlined, their persistence and bioaccumulation potential were highlighted. How MPs act as carriers of endocrine-disrupting chemicals, interfering with hormonal systems and potentially disrupting children's physiological development was elucidated subsequently. Special emphasis is placed on the mechanisms by which MPs alter gut microbial communities, leading to dysbiosis that may compromise immune function and metabolic processes in children. By synthesizing recent advances in toxicology, microbiology, and pediatric research, present review amalgamates insights from contemporary studies, elaborates the comprehensive health risks posed by MP exposure during critical developmental periods, underscoring the urgent need for targeted preventive and regulatory measures to mitigate MP-related health hazards and promote child health. We aim to provide a scientific foundation for future research directions of MPs exposure and the development of effective intervention strategies.

PMID:41960410 | PMC:PMC13057501 | DOI:10.3389/fpubh.2026.1755497

J Toxicol. 2026 Apr 6;2026:4669316. doi: 10.1155/jt/4669316. eCollection 2026.

ABSTRACT

Microplastics (MPs) pollution is a global concern due to their widespread persistence, occurrence, and toxicity to aquatic organisms. Fish are most vulnerable to MPs due to their feeding habits and ecological niches. This review critically synthesizes current evidences on MPs induced disruptions of key physiological functions and behavioral patterns in fish, with an emphasis on the underlying mechanistic pathways and biological consequences. MPs originate from various sources, entering aquatic systems and being ingested by fish directly or via trophic transfer. A prominent effect is growth inhibition commonly caused by gastrointestinal damage, impaired nutrient absorption, and metabolic stress. Moreover, it causes several hematobiochemical disruptions including anemia, leukocyte fluctuations, and biochemical and enzymatic imbalances that are connected to oxidative stress and immunosuppression. MPs also disrupt reproductive performances of fish through altering gonadosomatic index, inducing endocrine disruptions, dysregulating hypothalamic-pituitary-gonadal axis genes, and reducing fertilization and hatching success, with several transgenerational effects. Furthermore, MPs can induce oxidative stress through overproduction of reactive oxygen species (ROS) and modulation of antioxidant enzymes, along with dysregulation of immune and inflammatory responses. Behavioral alterations include reduced swimming performance and changes in feeding and reproductive behavior, which are linked to neurotoxicity and impairment of energy metabolism. Although a limited number of studies suggest species-specific effects, most studies highlight significant adverse impacts on fish health. Hence, this review and meta-analysis indicates that MPs substantially compromise fish physiology manifesting as poor growth, altered blood and metabolic profiles, impaired reproduction, and behavioral patterns. By integrating sources and transport pathways to physiological and behavioral outcomes, this review provides a comprehensive summary to inform ecological risk assessment and management of MPs in fisheries and aquatic ecosystems.

PMID:41953324 | PMC:PMC13054136 | DOI:10.1155/jt/4669316

Int J Reprod Biomed. 2026 Mar 30;24(1):13-22. doi: 10.18502/ijrm.v24i1.20993. eCollection 2026 Jan.

ABSTRACT

BACKGROUND: 7,12-dimethylbenz(a)anthracene (DMBA) is a pervasive environmental polycyclic aromatic hydrocarbon that exerts genotoxic and endocrine-disrupting effects in female reproductive tissues, largely through oxidative stress and induction of apoptosis. Ivermectin, a food and drug administration-approved antiparasitic agent, has emerging anti-inflammatory and antioxidant properties.

OBJECTIVE: We evaluated whether Ivermectin could protect the ovarian and uterine tissues against DMBA-induced injury.

MATERIALS AND METHODS: In this experimental study, 20 female Wistar rats (8 wk, 210 $\pm$ 5 gr) were divided into 4 groups (n = 5/each): control, Ivermectin (1 mg/kg), DMBA (single 80 mg/kg dose), and DMBA + Ivermectin (same dosage). After 8 wk, sex hormones (estradiol, progesterone, testosterone) were measured by enzyme-linked immunosorbent assay. Oxidative stress markers (malondialdehyde, superoxide dismutase activity, and total antioxidant capacity) were assayed. Ovarian tissue was analyzed for apoptosis-related gene expression (Bax, Bcl-2, Caspase-3, p53), and uterine and ovarian tissues were evaluated for histopathological changes by hematoxylin and eosin staining.

RESULTS: Our findings showed that DMBA induced significant oxidative stress and tissue damage, along with hormone disruption and upregulation of pro-apoptotic genes. In contrast, Ivermectin co-treatment largely reversed these changes, such as reducing the serum malondialdehyde and increasing superoxide dismutase and total antioxidant capacity. Moreover, the hormone level balance significantly shifted toward control values. Histopathological examination showed DMBA-induced ovarian damage and uterine epithelial degeneration, which were attenuated by Ivermectin.

CONCLUSION: Ivermectin significantly ameliorated DMBA-induced oxidative damage, endocrine disruption, and apoptotic signaling in female rats. These findings suggest Ivermectin's potential for protecting the reproductive tissues from environmental toxin injury.

PMID:41952867 | PMC:PMC13054294 | DOI:10.18502/ijrm.v24i1.20993

J Toxicol. 2026 Apr 6;2026:4669316. doi: 10.1155/jt/4669316. eCollection 2026.

ABSTRACT

Microplastics (MPs) pollution is a global concern due to their widespread persistence, occurrence, and toxicity to aquatic organisms. Fish are most vulnerable to MPs due to their feeding habits and ecological niches. This review critically synthesizes current evidences on MPs induced disruptions of key physiological functions and behavioral patterns in fish, with an emphasis on the underlying mechanistic pathways and biological consequences. MPs originate from various sources, entering aquatic systems and being ingested by fish directly or via trophic transfer. A prominent effect is growth inhibition commonly caused by gastrointestinal damage, impaired nutrient absorption, and metabolic stress. Moreover, it causes several hematobiochemical disruptions including anemia, leukocyte fluctuations, and biochemical and enzymatic imbalances that are connected to oxidative stress and immunosuppression. MPs also disrupt reproductive performances of fish through altering gonadosomatic index, inducing endocrine disruptions, dysregulating hypothalamic-pituitary-gonadal axis genes, and reducing fertilization and hatching success, with several transgenerational effects. Furthermore, MPs can induce oxidative stress through overproduction of reactive oxygen species (ROS) and modulation of antioxidant enzymes, along with dysregulation of immune and inflammatory responses. Behavioral alterations include reduced swimming performance and changes in feeding and reproductive behavior, which are linked to neurotoxicity and impairment of energy metabolism. Although a limited number of studies suggest species-specific effects, most studies highlight significant adverse impacts on fish health. Hence, this review and meta-analysis indicates that MPs substantially compromise fish physiology manifesting as poor growth, altered blood and metabolic profiles, impaired reproduction, and behavioral patterns. By integrating sources and transport pathways to physiological and behavioral outcomes, this review provides a comprehensive summary to inform ecological risk assessment and management of MPs in fisheries and aquatic ecosystems.

PMID:41953324 | PMC:PMC13054136 | DOI:10.1155/jt/4669316

Front Microbiol. 2026 Mar 23;17:1783630. doi: 10.3389/fmicb.2026.1783630. eCollection 2026.

ABSTRACT

Potassium sorbate (PS) is a widely used antimicrobial additive employed as a preservative in food, cosmetics, and animal feed. Early childhood represents a critical developmental window characterized by rapid growth, immune system maturation, gut microbiota establishment, and physiological homeostasis development, which may be particularly vulnerable to chemical exposures (during which chemical exposures may exert heightened impacts). Nevertheless, the effects of PS on childhood development and gut microbiota remain poorly understood, and its potential trans-generational effects have yet to be elucidated. In this study, we employed Drosophila melanogaster, an established model for studying evolutionarily conserved aspects of development, metabolism, and host-microbiota interactions, to systematically evaluate PS toxicity across multiple parameters: developmental dynamics, gut microbiota composition, gene regulation in adulthood, and trans-generational effects. Our findings demonstrate a dose-dependent biphasic response: while low-dose PS exposure (25 mg/L) accelerated larval pupation and adult emergence, suggesting a potential growth-promoting effect, high-dose exposure (≥ 500 mg/L) significantly delayed development and reduced adult lifespan (observed in females at 1,000 and males at 500-1,000 mg/L). Notably, trans-generational analysis revealed persistent developmental delays in the F1 generation, with offspring of 1,000 mg/L-exposed parents showing prolonged larval pupation time despite normal adult emergence timelines, indicative of partial developmental recovery. Mechanistically, high-dose PS disrupted endocrine signaling and altered expression of key developmental pathway regulators (EcR, InR, TOR, and E74B). These transcriptional changes were largely reversible in offspring, further supporting a similar gradually wash out recovery. While gut microbiota remained stable in exposed parents, offspring of 1,000 mg/L-exposed flies had significant microbiome alterations, highlighting clear trans-generational dysbiosis. This study provides new evidence that PS exposure during a sensitive developmental period in D. melanogaster can perturb development and gut microbial homeostasis across generations, offering insights relevant to understanding how early-life chemical exposures might influence conserved biological processes in higher organisms.

PMID:41948045 | PMC:PMC13050859 | DOI:10.3389/fmicb.2026.1783630

Toxicol Ind Health. 2026 Apr 7:7482337261439550. doi: 10.1177/07482337261439550. Online ahead of print.

ABSTRACT

4-Nonylphenol (4-NP), an endocrine disruptor, is known to induce mutagenic, toxic, or carcinogenic effects, including testicular toxicity via inducing oxidative stress and apoptosis. The objective of this work was to determine the capacity of lycopene (LC) and gallic acid (GA) to protect testicular histological structure, biochemical responses, and semen parameters in rats exposed to 4-NP. In this 28-day dietary trial, six groups (n= 6 per group) received treatment via oral gavage: a control (corn oil, 2 mL/kg/day), LC (10 mg/kg body weight (BW)/day), GA (50 mg/kg BW/day), 4-NP (125 mg/kg BW/day), LC + 4-NP (LC followed by 4-NP), and GA + 4-NP (GA followed by 4-NP) groups. The results indicated that 4-NP administration adversely affects the final body weight, testicular histology, seminiferous epithelium heights (SEHs) (4-NP: 57.95 ± 0.49, p: 0.000), follicle-stimulating hormone (FSH) level, testis antioxidant capacity, testis malondialdehyde (MDA) level, and sperm viability and morphology. LC and GA supplementation significantly improved SEHs, activities of testis superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), and sperm viability compared to the 4-NP group. Moreover, LC and GA exposures decreased histopathological lesions, including germinal epithelial degeneration, vacuolization, immature germ cells in the tubular lumen, and congestion in the interstitial area. Furthermore, they lowered TUNEL-positive cell counts and tubule percentages, testicular MDA levels, and abnormal sperm percentages. To our knowledge, this study provides one of the first systematic comparisons of lycopene and gallic acid in protecting against 4-NP-induced testicular toxicity under identical experimental conditions. The findings suggest that both compounds preserve testicular structure and function through their antioxidant and anti-apoptotic properties.

PMID:41947323 | DOI:10.1177/07482337261439550

Food Sci Nutr. 2026 Apr 4;14(4):e71692. doi: 10.1002/fsn3.71692. eCollection 2026 Apr.

ABSTRACT

Salidroside, a bioactive compound from Rhodiola rosea, shows potential in managing polycystic ovary syndrome (PCOS), a common endocrine-metabolic disorder. This study explored its therapeutic effects and mechanisms using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model and granulosa cells (GCs). Salidroside was found to restore estrous cyclicity, improve ovarian morphology, and rebalance serum hormone levels. Mechanistically, it suppressed ROS-mediated AKT/NF-κB signaling, inhibited NLRP3 inflammasome activation, and reduced proinflammatory cytokines. Network pharmacology and molecular docking identified AKT as a core target, validated by CETSA and DARTS assays. Furthermore, salidroside disrupted NLRP3-driven latent TGF-β1 (LAP-TGFβ1) activation, downregulated TGF-β-SMAD2/3 signaling, and attenuated ovarian fibrosis along with abnormal hyaluronan synthase 2 (HAS2) expression. These results highlight salidroside as a promising natural candidate for alleviating PCOS through coordinated anti-inflammatory and antifibrotic mechanisms.

PMID:41948383 | PMC:PMC13052134 | DOI:10.1002/fsn3.71692

Environ Health Insights. 2026 Apr 3;20:11786302261435748. doi: 10.1177/11786302261435748. eCollection 2026.

ABSTRACT

BACKGROUND: Global literature indicates that polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), types of brominated flame retardants (BFRs), are increasingly found in children's plastic products. These products are widely sold in South Africa. PBDEs and HBCDD are persistent organic pollutants (POPs) banned under the Stockholm Convention due to their severe health impacts, including endocrine disruption, neurotoxicity, and cancer. Information about chemicals present in these plastic products is necessary to inform risk reduction measures.

METHODS: This study assessed the availability and accessibility of information on POP-BFRs in children's plastic products in South Africa to enhance stakeholders' capacity to implement risk reduction measures. The study was guided by the chemicals-in-products (CiP) information-sharing framework developed by the United Nations Environment Programme (UNEP) in 2015. Data collection involved in-depth interviews and an online survey. South African stakeholders participated, including those involved in manufacturing, regulation, and advocacy (n = 10) and consumers (n = 44). Data was analyzed thematically using NVivo.

RESULTS: CiP information on POP-BFRs in children's plastic products was largely unavailable. Regulatory and advocacy stakeholders had limited general information on POP-BFRs and the associated risks. Additionally, they had limited access to POP-BFRs information, while consumers had none.

CONCLUSION: National and international coordinated actions are necessary to close the POP-BFRs information gaps. The South African government should develop and enforce an overarching chemical legislation, establish a national chemical register, and require full disclosure of CiP. UNEP should establish a global standardized system for CiP information under the 2023 Global Framework on Chemicals.

PMID:41948132 | PMC:PMC13051110 | DOI:10.1177/11786302261435748

Braz J Biol. 2026 Apr 3;86:e303146. doi: 10.1590/1519-6984.303146. eCollection 2026.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, leading cause of female infertility, disrupted estrous cycles, hormonal dysregulation, and abnormal ovarian morphology. This study aimed to evaluate the restorative effects of Thai Mucuna pruriens (TMP) seed extract on reproductive, hormonal, and fertility impairments in a PCOS rat model induced by letrozole. Following PCOS induction, female rats received TMP extract at 150, 300, and 600 mg/kg BW for 30 consecutive days. Untreated PCOS rats displayed persistent diestrus, hormonal dysregulation, and polycystic ovaries, and no pregnancies were observed. After TMP treatment, especially at 300 mg/kg BW, significantly reversed these impairments: estrous cyclicity normalized, hormonal profiles improved (increasing FSH and estradiol, decreasing LH and testosterone levels), and ovarian histology showed active folliculogenesis and reappearance of multiple corpus lutea. In addition, TMP could reduce the body weight and downregulate the ovarian androgen receptor (AR), estrogen receptor alpha (ERα), and tumor necrosis factor-alpha (TNF-α) protein expression. Moreover, TMP restored the fertility index and promoted embryo implantation, comparable to control animals. In conclusion, Thai Mucuna pruriens seed extract, particularly at 300 mg/kg, effectively reversed the reproductive, endocrine, and fertility impairments in letrozole-induced PCOS animal model, suggesting its promising potential as a phytotherapeutic agent for managing PCOS-associated reproductive dysfunction.

PMID:41950117 | DOI:10.1590/1519-6984.303146

Int Ophthalmol. 2026 Apr 8;46(1):196. doi: 10.1007/s10792-026-04068-w.

ABSTRACT

BACKGROUND: Autoimmune Retinopathy (AIR) is a rare, immune-mediated retinal degeneration caused by circulating autoantibodies targeting retinal antigens. Although classically associated with photoreceptor loss, multiple clinical and experimental studies suggest broader inner retinal involvement, including retinal ganglion cells.

METHODS: This review proposes a novel, hypothesis-generating model based on existing literature, exploring whether AIR may contribute to circadian disruption and sexual dysfunction-particularly erectile dysfunction (ED)-through immune-mediated injury to melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs).

RESULTS: ipRGCs project to the suprachiasmatic nucleus (SCN) and are essential for synchronizing circadian rhythms and regulating neuroendocrine function. While direct evidence of ipRGC damage in AIR is lacking, ipRGC pathway dysfunction has been reported in glaucoma and diabetic retinopathy-conditions that share pathological mechanisms with AIR. Circadian misalignment may disrupt testosterone secretion, melatonin rhythms, and nitric oxide signaling, all of which are implicated in ED.

CONCLUSION: This interdisciplinary framework integrates ocular immunology, circadian biology, and sexual medicine to highlight a potentially overlooked systemic dimension of AIR. Future studies are warranted to evaluate ipRGC integrity and circadian-endocrine markers in AIR patients and validate this conceptual pathway.

PMID:41949765 | DOI:10.1007/s10792-026-04068-w

Environ Int. 2026 Apr 3;210:110235. doi: 10.1016/j.envint.2026.110235. Online ahead of print.

ABSTRACT

BACKGROUND: Adolescence is the critical period for the development of peak bone mass. Per- and polyfluoroalkyl substances (PFAS) are widespread endocrine disruptors that may disturb skeletal development, but evidence in Nordic adolescents is limited.

OBJECTIVES: To evaluate sex-specific associations between serum PFAS and areal bone mineral density (aBMD) Z-scores among Norwegian adolescents.

METHODS: This cross-sectional study utilised data from Fit Futures 1 (2010-2011), a cohort of adolescents in Northern Norway. Eighteen serum PFAS were quantified, and aBMD Z-scores (femoral neck, total hip, total body) were calculated using dual-energy X-ray absorptiometry. We used multivariable linear regression and mixture analyses (quantile g-computation and Bayesian kernel machine regression) to estimate sex-specific associations.

RESULTS: Among 889 participants (421 girls and 468 boys; mean age 16.2 years), eight PFAS had detection rates >70%. The sum of linear and branched perfluorooctane sulfonic acid (ΣPFOS) had the highest median concentration (6.23 ng/ml). Perfluorononanoic acid (PFNA) (β = -0.16 per doubling, 95% CI: -0.26, -0.06) and perfluorodecanoic acid (PFDA) (β = -0.15 per doubling, 95% CI: -0.24, -0.06) showed consistent inverse association with total body aBMD. Mixture analyses suggested modest inverse overall mixture estimates, but 95% confidence intervals crossed the null. Sex-stratified analyses suggested that estimates tended to be more negative in boys than in girls.

CONCLUSIONS: Higher concentrations of several PFAS, particularly PFNA and PFDA, were modestly associated with lower aBMD Z-scores in Norwegian adolescents, most consistently for total body aBMD. Evidence for mixture effects and sex-specific differences was limited, although inverse associations tended to be more pronounced in boys. Longitudinal studies are needed to clarify temporal relationships and long-term skeletal impacts.

PMID:41950633 | DOI:10.1016/j.envint.2026.110235

J Adv Res. 2026 Apr 6:S2090-1232(26)00301-2. doi: 10.1016/j.jare.2026.04.024. Online ahead of print.

ABSTRACT

BACKGROUND: Epidemiological data indicate a significant global increase in both comorbidity and mutually induced rates between cardiovascular and neurological diseases. Among these, cardiovascular and cerebrovascular diseases share eleven co-localized loci. The critical role of the brain-heart axis in these processes has been increasingly recognized. This axis mediates dynamic bidirectional crosstalk via neuroendocrine, neuroimmune and related pathways, with key mediators including the hypothalamic-pituitary-adrenal (HPA) axis, gut-derived metabolites, extracellular vesicles (EVs), and autonomic nervous system (ANS). Conventional siloed care across cardiology and neurology specialties, alongside single-organ targeted therapies, fails to effectively disrupt the pathological vicious cycle of brain-heart interactions. Targeting key mediators of the brain-heart axis holds significant clinical potential for the treatment of neurological or cardiovascular diseases.

AIM OF REVIEW: This review systematically summarizes the key advances in brain-heart crosstalk over the past decade, delineates the direct neural pathways and indirect regulatory mechanisms between the two organs. Against this backdrop, we outline the clinical potential of nervous system-targeted strategies for cardiac disease and related neurological complications, alongside the broad promise of cardiac function optimization to modulate immune and endocrine pathways for cardio-cerebral comorbidity management.

KEY SCIENTIFIC CONCEPTS OF REVIEW: We discuss the mediators underlying brain-heart crosstalk, and delineate the distinct functional roles of the brain-heart axis across diverse cardiovascular diseases and psychiatric disorders, offering new conceptual frameworks for treating cardiocerebral comorbidities.

PMID:41951049 | DOI:10.1016/j.jare.2026.04.024

Biochimie. 2026 Apr 6;246:54-75. doi: 10.1016/j.biochi.2026.04.001. Online ahead of print.

ABSTRACT

Plastic production has become a global challenge, and its accelerated growth and widespread waste release justify the characterization of the current era as the "Age of Plastic". The concern is how additives or plastic degradation can impact different ecosystems and human health. Microplastics and certain plastic additives (e.g., phthalates) are already well-established in the literature as endocrine disruptors, posing a risk to human health. However, little is known about these issues regarding Nanoplastics (NPs). Therefore, this narrative review aimed to examine the potential biochemical disruptions induced by NPs across multiple organs and biological systems, while also considering their ecological, ecosystem-level, and human health risks. The NPs affect mitochondria and endoplasmic reticulum in experimental models and across various organs, affecting lipid, energy, and amino acid metabolism. In the environmental context, NPs can interfere with xylem/phloem transport, root absorptive function, and photosynthesis in both terrestrial and aquatic models. This raises concerns not only at the ecological levels, but also for production and the economy, with potential risks to human health through food. This review strengthens the understanding of environmental toxicology and the imminent risks of NPs on various ecosystems, highlighting the disruptions of these nanomolecules, whether isolated or adsorbed, to important catalytic pathways and metabolic pathways in an organ-wide manner.

PMID:41951121 | DOI:10.1016/j.biochi.2026.04.001

Biochimie. 2026 Apr 6;246:54-75. doi: 10.1016/j.biochi.2026.04.001. Online ahead of print.

ABSTRACT

Plastic production has become a global challenge, and its accelerated growth and widespread waste release justify the characterization of the current era as the "Age of Plastic". The concern is how additives or plastic degradation can impact different ecosystems and human health. Microplastics and certain plastic additives (e.g., phthalates) are already well-established in the literature as endocrine disruptors, posing a risk to human health. However, little is known about these issues regarding Nanoplastics (NPs). Therefore, this narrative review aimed to examine the potential biochemical disruptions induced by NPs across multiple organs and biological systems, while also considering their ecological, ecosystem-level, and human health risks. The NPs affect mitochondria and endoplasmic reticulum in experimental models and across various organs, affecting lipid, energy, and amino acid metabolism. In the environmental context, NPs can interfere with xylem/phloem transport, root absorptive function, and photosynthesis in both terrestrial and aquatic models. This raises concerns not only at the ecological levels, but also for production and the economy, with potential risks to human health through food. This review strengthens the understanding of environmental toxicology and the imminent risks of NPs on various ecosystems, highlighting the disruptions of these nanomolecules, whether isolated or adsorbed, to important catalytic pathways and metabolic pathways in an organ-wide manner.

PMID:41951121 | DOI:10.1016/j.biochi.2026.04.001

Environ Int. 2026 Apr 3;210:110235. doi: 10.1016/j.envint.2026.110235. Online ahead of print.

ABSTRACT

BACKGROUND: Adolescence is the critical period for the development of peak bone mass. Per- and polyfluoroalkyl substances (PFAS) are widespread endocrine disruptors that may disturb skeletal development, but evidence in Nordic adolescents is limited.

OBJECTIVES: To evaluate sex-specific associations between serum PFAS and areal bone mineral density (aBMD) Z-scores among Norwegian adolescents.

METHODS: This cross-sectional study utilised data from Fit Futures 1 (2010-2011), a cohort of adolescents in Northern Norway. Eighteen serum PFAS were quantified, and aBMD Z-scores (femoral neck, total hip, total body) were calculated using dual-energy X-ray absorptiometry. We used multivariable linear regression and mixture analyses (quantile g-computation and Bayesian kernel machine regression) to estimate sex-specific associations.

RESULTS: Among 889 participants (421 girls and 468 boys; mean age 16.2 years), eight PFAS had detection rates >70%. The sum of linear and branched perfluorooctane sulfonic acid (ΣPFOS) had the highest median concentration (6.23 ng/ml). Perfluorononanoic acid (PFNA) (β = -0.16 per doubling, 95% CI: -0.26, -0.06) and perfluorodecanoic acid (PFDA) (β = -0.15 per doubling, 95% CI: -0.24, -0.06) showed consistent inverse association with total body aBMD. Mixture analyses suggested modest inverse overall mixture estimates, but 95% confidence intervals crossed the null. Sex-stratified analyses suggested that estimates tended to be more negative in boys than in girls.

CONCLUSIONS: Higher concentrations of several PFAS, particularly PFNA and PFDA, were modestly associated with lower aBMD Z-scores in Norwegian adolescents, most consistently for total body aBMD. Evidence for mixture effects and sex-specific differences was limited, although inverse associations tended to be more pronounced in boys. Longitudinal studies are needed to clarify temporal relationships and long-term skeletal impacts.

PMID:41950633 | DOI:10.1016/j.envint.2026.110235

Environ Toxicol. 2026 Apr 6. doi: 10.1002/tox.70085. Online ahead of print.

ABSTRACT

Microplastics pollution is a widespread environmental issue in Latin America and the Caribbean (LAC), where factors such as urbanization, insufficient waste management, and coastal vulnerability may increase exposure risks. Microplastics can act as carriers for endocrine-disrupting chemicals (EDCs), but a comprehensive synthesis of region-specific evidence linking this contamination to reproductive health outcomes has been lacking. This systematic review examines the evidence regarding the impact of microplastics pollution on reproductive health across species in LAC, identifies contamination hotspots and exposure pathways, and highlights gaps in policy and research. Following PRISMA 2020 guidelines, we analyzed 30 peer-reviewed studies (2014-2024) from 12 LAC nations. Due to significant heterogeneity in study designs, populations, and outcomes, a narrative synthesis was conducted to integrate evidence from environmental monitoring, animal toxicology, and human biomonitoring studies. Risk of bias was assessed using design-specific tools. The evidence indicates widespread microplastics contamination in LAC, with notable hotspots in coastal Colombia (4.54 particles/m²), Argentine riverine systems (30 780 particles/m²), and Mexican groundwater (18.3 particles/L). Overall, 82% of assessed sites were classified as "Dirty" to "Extremely Dirty." Animal studies reported that microplastics exposure was associated with reproductive toxicity, including reduced sperm concentration and motility, ovarian fibrosis, and polycystic ovary syndrome (PCOS)-like phenotypes. Human biomarker studies found elevated urinary bisphenol A (BPA) levels in pregnant women from Caribbean countries, correlating with altered gonadotropin ratios. Dietary intake, particularly from seafood and beverages, was identified as a primary exposure pathway, while inhalable particles in urban air posed additional risks. No LAC country has established enforceable microplastics thresholds for drinking water or standardized biomonitoring protocols. This systematic review suggests that microplastics pollution is prevalent in LAC environments and is associated with adverse reproductive outcomes in animal models. Preliminary human data indicate potential exposure-related endocrine effects, though causal inference is limited by the absence of direct microplastic exposure measurements and reliance on cross-sectional EDC biomarker studies. The findings underscore the need for expanded biomonitoring, harmonized research methodologies, and region-specific policy development to better understand and address potential public health implications.

PMID:41943499 | DOI:10.1002/tox.70085

Nat Rev Gastroenterol Hepatol. 2026 Apr 7. doi: 10.1038/s41575-026-01188-7. Online ahead of print.

ABSTRACT

Human liver tissue has been found to contain microplastics and nanoplastics (MNPs), with evidence that hepatic MNP accumulation has markedly increased over the past 10 years, prompting critical questions regarding their potential causal role in liver disease. In cell-based and murine models, MNP exposure can trigger oxidative stress, fibrogenesis and inflammation, pathological features that resemble those of advanced liver disease, suggesting shared mechanistic pathways. Furthermore, the capacity for MNPs to act as vectors for microbial pathogens, antimicrobial resistance, endocrine-disrupting chemicals and carcinogenic additives might have important implications for liver pathology. This Perspective examines emerging evidence on the consequences of MNPs for liver health and disease, introducing the concept of plastic-induced liver injury. By highlighting critical methodological bottlenecks, key knowledge gaps and unmet research priorities, it lays out a road map for the emerging field of environmental hepatology.

PMID:41946921 | DOI:10.1038/s41575-026-01188-7

Environ Sci Pollut Res Int. 2026 Apr 7. doi: 10.1007/s11356-026-37723-x. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used for their resistance to heat, water, and oil, which also confers exceptional environmental persistence and promotes accumulation across ecosystems and organisms. Strong carbon-fluorine bonding and extensive industrial usage contribute toward widespread contamination affecting water quality, food safety, and soil integrity across global environments. PFAS enter the environment through industrial discharges, wastewater treatment plants, landfills, firefighting foams, and consumer products such as non-stick cookware, water-repellent textiles, food packaging, and personal care items. They contaminate water, soil, and air and may enter agricultural systems, thereby influencing crop quality and food safety. Human exposure occurs primarily through consumption of contaminated drinking water and food, with additional exposure via inhalation, skin contact, and ingestion of dust. Freshwater organisms frequently exhibit higher PFAS concentrations than marine species, increasing dietary exposure risks. PFAS exposure has been associated with immune suppression, endocrine disruption, liver damage, reproductive effects, elevated cholesterol levels, and cancer. Ecologically, PFAS alter microbial community structure and accumulate within wildlife and food webs. Conventional water treatment processes show minimal effectiveness against PFAS, intensifying research on adsorbent- and hybrid treatment-based remediation under the pollutant toxic ions and molecules research theme. This review emphasizes progress with activated carbon (AC), ion exchange resins, mineral sorbents, membranes, and destruction technologies, as well as emerging materials such as metal-organic frameworks, covalent organic frameworks, and polymeric or nanocomposite sorbents, while highlighting performance constraints, regeneration challenges, operational limitations, and critical gaps for scalable and sustainable PFAS management.

PMID:41944997 | DOI:10.1007/s11356-026-37723-x

Environ Toxicol. 2026 Apr 6. doi: 10.1002/tox.70085. Online ahead of print.

ABSTRACT

Microplastics pollution is a widespread environmental issue in Latin America and the Caribbean (LAC), where factors such as urbanization, insufficient waste management, and coastal vulnerability may increase exposure risks. Microplastics can act as carriers for endocrine-disrupting chemicals (EDCs), but a comprehensive synthesis of region-specific evidence linking this contamination to reproductive health outcomes has been lacking. This systematic review examines the evidence regarding the impact of microplastics pollution on reproductive health across species in LAC, identifies contamination hotspots and exposure pathways, and highlights gaps in policy and research. Following PRISMA 2020 guidelines, we analyzed 30 peer-reviewed studies (2014-2024) from 12 LAC nations. Due to significant heterogeneity in study designs, populations, and outcomes, a narrative synthesis was conducted to integrate evidence from environmental monitoring, animal toxicology, and human biomonitoring studies. Risk of bias was assessed using design-specific tools. The evidence indicates widespread microplastics contamination in LAC, with notable hotspots in coastal Colombia (4.54 particles/m²), Argentine riverine systems (30 780 particles/m²), and Mexican groundwater (18.3 particles/L). Overall, 82% of assessed sites were classified as "Dirty" to "Extremely Dirty." Animal studies reported that microplastics exposure was associated with reproductive toxicity, including reduced sperm concentration and motility, ovarian fibrosis, and polycystic ovary syndrome (PCOS)-like phenotypes. Human biomarker studies found elevated urinary bisphenol A (BPA) levels in pregnant women from Caribbean countries, correlating with altered gonadotropin ratios. Dietary intake, particularly from seafood and beverages, was identified as a primary exposure pathway, while inhalable particles in urban air posed additional risks. No LAC country has established enforceable microplastics thresholds for drinking water or standardized biomonitoring protocols. This systematic review suggests that microplastics pollution is prevalent in LAC environments and is associated with adverse reproductive outcomes in animal models. Preliminary human data indicate potential exposure-related endocrine effects, though causal inference is limited by the absence of direct microplastic exposure measurements and reliance on cross-sectional EDC biomarker studies. The findings underscore the need for expanded biomonitoring, harmonized research methodologies, and region-specific policy development to better understand and address potential public health implications.

PMID:41943499 | DOI:10.1002/tox.70085

Environ Sci Pollut Res Int. 2026 Apr 7. doi: 10.1007/s11356-026-37723-x. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used for their resistance to heat, water, and oil, which also confers exceptional environmental persistence and promotes accumulation across ecosystems and organisms. Strong carbon-fluorine bonding and extensive industrial usage contribute toward widespread contamination affecting water quality, food safety, and soil integrity across global environments. PFAS enter the environment through industrial discharges, wastewater treatment plants, landfills, firefighting foams, and consumer products such as non-stick cookware, water-repellent textiles, food packaging, and personal care items. They contaminate water, soil, and air and may enter agricultural systems, thereby influencing crop quality and food safety. Human exposure occurs primarily through consumption of contaminated drinking water and food, with additional exposure via inhalation, skin contact, and ingestion of dust. Freshwater organisms frequently exhibit higher PFAS concentrations than marine species, increasing dietary exposure risks. PFAS exposure has been associated with immune suppression, endocrine disruption, liver damage, reproductive effects, elevated cholesterol levels, and cancer. Ecologically, PFAS alter microbial community structure and accumulate within wildlife and food webs. Conventional water treatment processes show minimal effectiveness against PFAS, intensifying research on adsorbent- and hybrid treatment-based remediation under the pollutant toxic ions and molecules research theme. This review emphasizes progress with activated carbon (AC), ion exchange resins, mineral sorbents, membranes, and destruction technologies, as well as emerging materials such as metal-organic frameworks, covalent organic frameworks, and polymeric or nanocomposite sorbents, while highlighting performance constraints, regeneration challenges, operational limitations, and critical gaps for scalable and sustainable PFAS management.

PMID:41944997 | DOI:10.1007/s11356-026-37723-x

Toxicology. 2026 Apr 5;524:154468. doi: 10.1016/j.tox.2026.154468. Online ahead of print.

ABSTRACT

Obesity is a major global health challenge associated with a cluster of comorbidities, including metabolic syndrome and type 2 diabetes, necessitating a deeper understanding of the environmental factors contributing to this epidemic. This study investigated the in vitro adipogenic/lipogenic potential of paracetamol and its in vivo endocrine and metabolic modulating effects following prenatal exposure. Using the 3T3-L1 preadipocyte model, cells were exposed to paracetamol at physiologically relevant concentrations. Results demonstrated that paracetamol promoted lipid accumulation and upregulated G3PDH activity. Furthermore, low concentrations significantly increased the protein expression of key adipogenic regulators (PPARγ, C/EBPα, LPL, and SREBP1), suggesting interference with transcriptional cascades governing adipogenesis and lipogenesis. To assess in vivo effects, pregnant CD1 mice were exposed to paracetamol at three human relevant doses (Cmax/10, Cmax, and Cmax×10). In male F1 offspring, prenatal exposure resulted in increased anogenital distance and a higher incidence of sperm morphological abnormalities, indicating reproductive developmental alterations despite unchanged circulating hormone levels. Metabolically, offspring exhibited dyslipidemia characterized by elevated serum triglycerides and total cholesterol. Although body weight and glucose tolerance remained unaffected, lipidomic profiling of epididymal adipose tissue revealed pronounced remodeling, including the accumulation of neutral lipids and altered membrane phospholipid composition. This was accompanied by the upregulation of the adipogenic genes Pparγ, Lpl, and Fasn in adipose tissue. Collectively, these findings suggest that paracetamol may act as an endocrine modulator and metabolic disruptor when exposed prenatally, inducing latent metabolic dysregulation that may predispose offspring to metabolic syndrome later in life, even in the absence of overt obesity.

PMID:41946439 | DOI:10.1016/j.tox.2026.154468

J Biosci Bioeng. 2026 Apr 6:S1389-1723(26)00097-6. doi: 10.1016/j.jbiosc.2026.03.004. Online ahead of print.

ABSTRACT

Phthalate esters, widely used as plasticizers in plastic manufacturing, are known for their endocrine-disrupting effects. γ-Oryzanol derivatives, functional lipids composed of sterol and ferulic acid esters, possess diverse biological activities. In this study, we cloned and heterologously expressed a lipase-encoding gene (lipO745) from Aspergillus oryzae RIB40, deleting a 23-amino-acid N-terminal signal peptide, in Pichia pastoris using the pPICZαC vector. The resulting recombinant enzyme (rLipO745Δ23) was successfully secreted as an active extracellular protein. The purified recombinant lipase exhibited an apparent molecular mass of approximately 65 kDa, as determined using SDS-PAGE. Substrate specificity assays using p-nitrophenyl (pNP) esters (C2-C16) revealed that pNP butyrate (pNP-C4) was hydrolyzed most efficiently, with a specific activity of 369.2 ± 6.6 nmol·mL^-1 mg^-1. rLipO745Δ23 catalyzed the conversion of dibutyl phthalate (DBP) to monobutyl phthalate (MBP) without further degradation to phthalic acid, and exhibited an activity of 7.24 ± 0.61 nmol·mL^-1 mg^-1 toward DBP. The kinetic parameters (K_m and k_cat) were 0.66 ± 0.1 mM and 37.8 ± 6.4 s^-1, respectively, for pNP-C4 substrate, and 0.40 ± 0.05 mM and 1.30 ± 0.23 s^-1, respectively, for DBP. Moreover, rLipO745Δ23 showed detectable hydrolytic activity toward γ-oryzanol, including cycloartenyl ferulate, a conjugate of ferulic acid and triterpene alcohol. Notably, β-sitosterol, a major hydrolysate of phytosterol type γ-oryzanol, did not inhibit enzymatic activity. These findings highlight the potential of rLipO745Δ23 as a versatile biocatalyst for the enzymatic degradation of phthalates and γ-oryzanol derivatives in environmental and industrial applications.

PMID:41946630 | DOI:10.1016/j.jbiosc.2026.03.004

Nat Rev Gastroenterol Hepatol. 2026 Apr 7. doi: 10.1038/s41575-026-01188-7. Online ahead of print.

ABSTRACT

Human liver tissue has been found to contain microplastics and nanoplastics (MNPs), with evidence that hepatic MNP accumulation has markedly increased over the past 10 years, prompting critical questions regarding their potential causal role in liver disease. In cell-based and murine models, MNP exposure can trigger oxidative stress, fibrogenesis and inflammation, pathological features that resemble those of advanced liver disease, suggesting shared mechanistic pathways. Furthermore, the capacity for MNPs to act as vectors for microbial pathogens, antimicrobial resistance, endocrine-disrupting chemicals and carcinogenic additives might have important implications for liver pathology. This Perspective examines emerging evidence on the consequences of MNPs for liver health and disease, introducing the concept of plastic-induced liver injury. By highlighting critical methodological bottlenecks, key knowledge gaps and unmet research priorities, it lays out a road map for the emerging field of environmental hepatology.

PMID:41946921 | DOI:10.1038/s41575-026-01188-7

Front Cell Dev Biol. 2026 Mar 19;14:1788805. doi: 10.3389/fcell.2026.1788805. eCollection 2026.

ABSTRACT

BACKGROUND: Male infertility (MI) impacts about one in seven couples globally, involving complex gene-environment interactions. Environmental pollutants may disrupt spermatogenesis via mitochondrial dysfunction, but key targets and mechanisms are unclear. Integrating multi-omics with computational toxicology offers a novel strategy to decipher these interactions.

METHODS: We integrated blood transcriptomics from MI patients, GWAS summary statistics, and QTL data (methylation, expression, protein). MI-related mitochondrial genes were identified through differential expression analysis, followed by enrichment and PPI network analysis. SMR approach was employed to assess genetic causality between molecular levels of genes and MI risk, using cis-QTLs as instrumental variables and applying the HEIDI test (p < 0.05) to distinguish pleiotropy from linkage. The candidate gene FIS1 was functionally validated in vitro by siRNA knockdown in GC-1 spg cells. Reverse network toxicology was then used to screen environmental pollutants potentially targeting FIS1, with candidate compounds selected from the CTD based on unidirectional inhibitory effects on FIS1, high bioaccumulation potential (Log P > 5), and predicted toxicity (mutagenicity, cytotoxicity, or endocrine disruption). Binding affinity was evaluated via molecular docking.

RESULTS: We identified 232 dysregulated mitochondrial genes in MI. SMR analysis revealed that FIS1 showed a consistent, significant protective association with MI risk across three molecular levels: DNA methylation (e.g., site cg19802458), gene expression, and plasma protein abundance. Clinical samples confirmed downregulated FIS1 expression in MI patients. In vitro, FIS1 knockdown in spermatogonial cells reduced mitochondrial membrane potential, elevated reactive oxygen species, decreased antioxidant enzyme activity, and significantly inhibited proliferation. Reverse toxicology screened six environmental pollutants predicted to target FIS1, including di (2-ethylhexyl) phthalate, bisphenol S, aflatoxin B1, and benzo [a]pyrene. Molecular docking confirmed stable binding of all six compounds to the FIS1 protein (ΔG < -5.0 kcal/mol), suggesting a direct mechanism for disrupting mitochondrial function.

CONCLUSION: By integrating multi-omics and computational toxicology, this study validates FIS1's causal protective role in male infertility, reveals its multi-level regulation, and predicts six targeting pollutants with preliminary experimental evidence. This framework offers new insights into gene-environment interactions and establishes a foundation for biomarker development and targeted interventions.

PMID:41938534 | PMC:PMC13044088 | DOI:10.3389/fcell.2026.1788805

ACS Omega. 2026 Mar 17;11(12):19782-19789. doi: 10.1021/acsomega.6c00246. eCollection 2026 Mar 31.

ABSTRACT

Endocrine-disrupting chemicals can interfere with thyroid hormone signaling and may contribute to adverse health outcomes. Among these, halogenated phenolic derivatives of household and personal care product (HPCP) ingredients are of increasing concern due to their structural resemblance to thyroid hormones. In this study, a comprehensive library of halogenated parabens, bisphenols, UV filters, and nonylphenols was evaluated for thyroid receptor (TR) modulatory activity using a GH3.TRE-Luc reporter assay. Halogenated bisphenol F derivatives displayed pronounced TR agonistic activity, with dichlorinated BPF emerging as the most potent agonist. In contrast, dihalogenated long-chain parabens, particularly dibrominated analogs, demonstrated antagonistic effects in the low micromolar range. Overall, our findings demonstrate that halogenation significantly influences TR modulation by phenolic HPCP ingredients, emphasizing the need for further investigation into their potential endocrine-disrupting impact.

PMID:41939347 | PMC:PMC13044685 | DOI:10.1021/acsomega.6c00246

Front Immunol. 2026 Mar 10;17:1708940. doi: 10.3389/fimmu.2026.1708940. eCollection 2026.

ABSTRACT

Tic Disorders (TDs) are common neurodevelopmental disorders characterized by complex pathophysiological mechanisms. A growing body of evidence in recent years suggests that immune system dysregulation plays a critical role in the pathogenesis and clinical course of TDs in a subset of pediatric patients. This review aims to systematically summarize the current understanding of the core mechanisms of immune dysregulation in pediatric TDs, potential biomarkers, and related therapeutic frontiers. We detail three core pathophysiological pathways, Post infectious autoimmunity, represented by the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) models. Its core mechanism involves the production of autoantibodies induced by molecular mimicry, which target basal ganglia neurons, such as cholinergic interneurons and dopamine receptors. Neuroinflammation is another critical pathway. This process involves T helper 17 (Th17) cell-mediated disruption of the blood-brain barrier and microglial activation. It is further characterized by elevated pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). Microbiota-gut-brain axis dysregulation, wherein gut dysbiosis and compromised intestinal barrier function influence central nervous system (CNS) function through the neuro immune endocrine network. Building upon this framework, we evaluate potential biomarkers across various dimensions, including the findings and limitations in serology (cytokines), cerebrospinal fluid analysis (oligoclonal bands, MCP-1), neuroimaging (volumetric changes in the basal ganglia and PET imaging of neuroinflammation), and genetics (variations in the IL-1RN gene). Finally, we discuss the evolution from conventional treatments to emerging immune-targeted therapies. This encompasses core immunomodulatory therapies (Intravenous Immunoglobulin (IVIG) and plasmapheresis) and promising future strategies, such as fecal microbiota transplantation (FMT), targeted B-cell therapies, and small-molecule anti-inflammatory drugs. In conclusion, a deeper understanding of the immunological basis of TDs is paving the way for the development of more precise diagnostic tools and novel, individualized immunomodulatory interventions.

PMID:41939897 | PMC:PMC13047447 | DOI:10.3389/fimmu.2026.1708940

Environ Pollut. 2026 Apr 4;398:128057. doi: 10.1016/j.envpol.2026.128057. Online ahead of print.

ABSTRACT

Endocrine-disrupting chemicals are recognized for their impact on fallopian tube function; however, epidemiological evidence linking phthalates to fallopian tube disorders is still limited. In this cross-sectional study within the Tongji Reproductive and Environmental (TREE) Cohort, we collected urine and follicular fluid (FF) samples from 291 infertile women aged 20 to 45 years with no history of sexually transmitted infections (STIs) or pelvic inflammatory disease (PID), and measured eight phthalate metabolites. Salpingitis cases (n = 62) were identified based on clinical diagnosis documented in medical records. Notably, residual confounding by STI/PID-related factors may still exist despite this exclusion. We evaluated associations with individual metabolites and mixtures using logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. In both crude and adjusted models, higher tertiles of monobenzyl phthalate (MBzP) in FF were positively associated with salpingitis (P for trend = 0.04). Upon adjusting for covariates, a per logarithm (ln)-unit rise in mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) levels in FF was linked to a 1.63-fold elevation (95% CI: 1.01, 2.64) in salpingitis odds. Furthermore, concentrations of monoethyl phthalate (MEP) in urine samples were positively correlated with salpingitis [adjusted model: 1.38 (1.06, 1.80)]. Additionally, the mixtures of phthalate metabolites in both urine and FF generally did not show significant associations with salpingitis. Stratified analyses revealed an increased odds of salpingitis associated with urinary mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) in women under 30 years of age (P for interaction = 0.03), with urinary MBzP in women with body mass index (BMI) ≥ 24 kg/m² and non-female factor infertility (P for interaction = 0.01), and with FF mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) in the female-factor infertility group (P for interaction = 0.02). These results indicate that certain phthalate metabolites in FF and urine show a positive correlation with salpingitis, underscoring the necessity for further research.

PMID:41942020 | DOI:10.1016/j.envpol.2026.128057

Food Res Int. 2026 Jun 1;233(Pt 1):118968. doi: 10.1016/j.foodres.2026.118968. Epub 2026 Mar 17.

ABSTRACT

Environmental endocrine disruptors, such as bisphenol A (BPA), pose significant threats to male reproductive health. Cordycepin, a bioactive nucleoside derived from Cordyceps militaris, has demonstrated antioxidant and bioregulatory effects; however, its protective role against BPA-induced reproductive toxicity remains insufficiently understood. This study investigated the protective role of cordycepin in male mice exposed to BPA through physiological, histological, metabolomic, microbiota-related, and molecular analyses. BPA exposure markedly decreased the average serum testosterone level (-59.3%), sperm count (-49.2%), and testis index (-28.1%), and increased the sperm abnormality rate (+72.4%). Cordycepin administration dose-dependently restored average testosterone level (up to +118% compared to BPA), improved sperm density and morphology, and recovered seminiferous epithelial thickness (+36.7%). At the molecular level, cordycepin attenuated BPA-induced suppression of PI3K, mTOR, and HIF-1α expression at both mRNA and protein levels. Metabolomic analysis revealed normalization of BPA-perturbed metabolites, including serine, glycine, and L-valine. Gut-microbiota analysis showed that cordycepin increased the abundance of beneficial genera Ruminococcus and Bacteroides, which positively correlated with reproductive parameters. Complementary in vitro assays confirmed that cordycepin exerted its protective effects by activating the PI3K/mTOR/HIF-1α signaling pathway. Overall, cordycepin effectively alleviated BPA-induced male reproductive toxicity by restoring endocrine balance, improving sperm quality and testicular structure, and modulating metabolic and microbial homeostasis. These findings suggest that cordycepin may be a promising candidate for mitigating reproductive damage caused by environmental toxicants.

PMID:41942214 | DOI:10.1016/j.foodres.2026.118968

BMC Pregnancy Childbirth. 2026 Apr 7. doi: 10.1186/s12884-026-08987-5. Online ahead of print.

ABSTRACT

BACKGROUND: Exposure to chemical products during pregnancy is a growing threat to maternal and fetal health.

OBJECTIVE: The aim of this study is to investigate the effectiveness of Motivational Interviewing (MI) based education in reducing the use of products that may contain chemicals among pregnant women and in creating a change in attitudes towards the use of these chemicals.

METHODS: The study was conducted using a pretest-posttest randomized controlled design with 130 pregnant women. Intervention group received three face-to-face MI based education sessions aimed at reducing the use of products that may contain chemicals. Participants reported using frequencies of personal care and domestic products that may contain chemicals. Attitudes toward avoiding potentially harmful chemicals were additionally measured using an Endocrine Disrupting Attitude Scale (EDAS).

RESULTS: A statistically significant difference was found when comparing the differences (pre-test-post-test) in personal care and domestic products that contain chemicals usage between the experimental and control groups p < 0.05. In the experimental group, a decrease in the use of most products was observed in the post-test. While the pretest EDAS mean scores of the pregnant women in the intervention and control groups were similar, the posttest EDAS mean scores increased. Results indicated a significant main effect in traction between group and time for EDAS (F13.06; η2 = .093, P < .001).

CONCLUSION: MI based education was an effective method to reduce the use of products that may chemicals and develop positive attitude towards protection against use of products.

TRIAL REGISTRATION: The study was registered retrospectively with the Clinical Trials Protocol Registration and Results System. NCT06380634. (registered 24.04.2024).

PMID:41942949 | DOI:10.1186/s12884-026-08987-5

Environ Sci Technol. 2026 Apr 6. doi: 10.1021/acs.est.6c00107. Online ahead of print.

ABSTRACT

The large-scale production and recycling of electric equipment have led to widespread contamination by persistent, bioaccumulative, and endocrine-disrupting brominated organic compounds. However, efficient methods for identifying these compounds in soil matrices remain limited. Here, a nontarget screening method was developed to detect characteristic bromine isotopic ions from mass spectrometry data acquired in data-independent analysis mode and applied to soil samples collected from e-waste dismantling sites in Taizhou (Zhejiang Province) and Guiyu (Guangdong Province), China. A total of 24 traditional and emerging polybrominated organic pollutants were identified, including Tetrabromobisphenol A (TBBPA) and its transformation products (TPs), brominated carbazoles (BCZs), bromoindoles (BIs), bromophenols (BPs), and hexabromocyclododecane (HBCDs). Six TBBPA TPs, BCZs, and BIs were identified for the first time in e-waste contaminated soils. Among these, TBBPA and its low-bromination homologues showed the highest detection rates and concentrations, reaching up to 4770 ng/g. Notably, six TBBPAs TPs were exclusively detected in Guiyu, while BCZs and BPs were found at all 12 sampling sites. HBCDs levels were lower than those of other e-waste sites. These findings highlight significant contamination by polybrominated compounds released through improper e-waste disassembly practices, providing critical data for monitoring and risk assessment.

PMID:41937607 | DOI:10.1021/acs.est.6c00107

Front Oncol. 2026 Mar 19;16:1784356. doi: 10.3389/fonc.2026.1784356. eCollection 2026.

ABSTRACT

INTRODUCTION: Tamoxifen is a cornerstone of endocrine therapy for estrogen receptor-positive breast cancer; however, its partial estrogen agonist activity in the endometrium predisposes patients to hyperplasia and, in some cases, malignant transformation. The molecular mechanisms underlying this tissue-specific adverse effect remain incompletely understood.

METHODS: We employed immortalized human endometrial epithelial cells to investigate the role of p53 in tamoxifen-induced proliferation. Cells were genetically manipulated to express wild-type (WT) or mutant p53 (R248Q), and ALKBH5 or REG1A was silenced or overexpressed using lentiviral constructs. A comprehensive set of molecular techniques-including quantitative reverse transcription PCR (qRT-PCR), Western blotting, chromatin immunoprecipitation (ChIP), luciferase reporter assays, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and functional proliferation assays (CCK-8 and colony formation)-was applied to dissect transcriptional and post-transcriptional regulatory mechanisms.

RESULTS: Tamoxifen promoted the recruitment of WT p53 to the ALKBH5 promoter, transcriptionally activating this m⁶A RNA demethylase. ALKBH5 subsequently erased m⁶A modifications from REG1A mRNA, preventing YTHDF2-mediated decay and thereby stabilizing REG1A expression. Elevated REG1A protein functioned as a negative feedback regulator, attenuating tamoxifen-induced proliferation. In stark contrast, the p53 R248Q mutant, despite retaining promoter-binding capacity, suppressed ALKBH5 transcription-potentially through altered cofactor recruitment-leading to increased m⁶A methylation of REG1A transcripts, enhanced YTHDF2-dependent degradation, and consequently, exaggerated cellular proliferation. Loss-of-function and genetic rescue experiments established that ALKBH5 is both necessary and sufficient to regulate REG1A mRNA stability, and that REG1A serves as the critical downstream effector mediating proliferative restraint under tamoxifen treatment.

CONCLUSIONS: Tamoxifen's anti-proliferative effects in endometrial epithelial cells are critically dependent on WT p53, which coordinates a protective epitranscriptomic regulatory axis. In contrast, mutant p53 disrupts this checkpoint and redirects tamoxifen signaling toward hyperproliferation. These findings establish a mechanistic link between hormonal signaling, p53 allelic status, and m⁶A-dependent post-transcriptional regulation. Although further in vivo validation is required, disruption of the ALKBH5-REG1A axis may contribute to heterogeneous endometrial responses to tamoxifen, thereby providing a conceptual framework for biomarker-oriented investigation.

PMID:41939469 | PMC:PMC13044134 | DOI:10.3389/fonc.2026.1784356

Mol Metab. 2026 Apr 2:102362. doi: 10.1016/j.molmet.2026.102362. Online ahead of print.

ABSTRACT

Cellular identity is fundamentally determined by the precise regulation of protein synthesis, which governs growth, differentiation, and function. In the pancreas, the balance between exocrine and endocrine cell types is critical for organ function, and the disruption of protein synthesis in these cells can lead to diseases such as exocrine insufficiency and diabetes. The specialized mRNA translation factor eukaryotic initiation factor 5A (eIF5A) has emerged as an essential regulator of on-demand protein synthesis in professional secretory cells. Here, we investigate the role of eIF5A-mediated mRNA translation in lineage specification during pancreas development. Using genetic mouse models, our studies reveal that loss of eIF5A results in a marked reduction of exocrine volume and a paradoxical expansion of the insulin-producing beta cell population. We reveal that these cellular changes are driven by impaired on-demand protein synthesis during the critical stage of pancreatic cell differentiation. Mechanistically, we show that eIF5A deficiency disrupts the synthesis of proteins critical for proper pathway signaling-most notably Notch-that instruct cell fate decisions. As a result, we observe impaired ductal branching and tip formation as well increased Ngn3+ endocrine progenitors within the ducts. These changes in lineage allocations directly contribute to decreased acinar cell and increased beta cell mass. Remarkably, eIF5A-deficient mice maintain elevated beta cell mass and exhibit preserved glucose tolerance despite severe exocrine deficiency. Collectively, our findings establish that eIF5A-mediated mRNA translation regulates critical developmental signaling pathways and reinforces the finding that disruptions in protein synthesis can reprogram cellular identity and drive disease pathogenesis.

PMID:41935829 | DOI:10.1016/j.molmet.2026.102362

Aquat Toxicol. 2026 Mar 31;295:107815. doi: 10.1016/j.aquatox.2026.107815. Online ahead of print.

ABSTRACT

Endocrine disruptors, ubiquitous in terrestrial and aquatic environments, have come under increased public and scientific scrutiny and are classified as substances of great concern for human health and the environment. The main objective of which is to determine the potential role of sodium fluoride (NaF) on rainbow trout health, with a particular interest in the thyroid hormone system, the immune system, and the development and behavior in early life stages. Rainbow trout (Oncorhynchus mykiss) embryos (265DD) were exposed for 15 days to NaF at 0, 0.5, 1, 5, 8 and 15 mg/L of F^-. After the first 15 day-exposure, larvae were divided into three batches (1) exposed to NaF for further 8 days at the same concentrations, (2) infected with the Infectious Hematopoietic Necrosis virus, or (3) held in clean water. Fish were monitored daily to follow their development, morphology and behavior and sampled after 15 or 23 days of exposure, with and without viral infection, to evaluate effects on the THS (eye development, thyroid) and their capacity of resistance to IHNV. Results show impaired growth (decrease in size and an increase in the rate of abnormalities rate) and significative behavior impact at 15 mg/L of F^- with a decrease of activity (speed, and light stress reaction). 5 mg/L of F^- caused delayed hatching, a decrease in virus-related mortality, an increase of thyroid follicles number, and increased photoreceptor layer thickness. Further analyses will determine the immunotoxicity of this potential ED by analyzing gene activity and blood parameters in older fish.

PMID:41936154 | DOI:10.1016/j.aquatox.2026.107815

J Reprod Immunol. 2026 Apr 1:104882. doi: 10.1016/j.jri.2026.104882. Online ahead of print.

ABSTRACT

Polycystic ovary syndrome (PCOS) is increasingly recognized as a disorder of impaired immune-endocrine homeostasis. Emerging evidence indicates that intestinal dysbiosis and microbial metabolite imbalance can activate pattern recognition receptors (PRRs), forming a PRR microbiota reproductive axis that contributes to PCOS pathophysiology. This review synthesizes current insights into how gut-derived signals, including LPS, peptidoglycans, SCFAs, bile acids, and tryptophan metabolites, modulate TLR-, NLR-, and RLR-mediated pathways to disrupt ovarian, endometrial, and systemic immune regulation. We further propose a unifying framework, the Reproductive Immune Tolerance Disruption Theory, which posits that chronic PRR activation shifts reproductive tract immunity from a tolerogenic to a low-grade inflammatory state, thereby promoting hyperandrogenism, anovulation, insulin resistance, and metabolic dysfunction. We also summarize recent multi-omics and immunometabolic studies that clarify the crosstalk between gut microbial signatures and innate immune signaling. Finally, we highlight precision strategies, including PRR-selective immunomodulation, microbiota-based therapies, and epigenetic metabolic interventions that hold translational potential for redefining PCOS management. Understanding PRR-driven microbial immunomodulation provides a mechanistic framework for reconciling endocrine, metabolic, and reproductive abnormalities in PCOS, guiding the development of targeted therapeutic approaches.

PMID:41935935 | DOI:10.1016/j.jri.2026.104882

Ultrason Sonochem. 2026 Mar 28;129:107830. doi: 10.1016/j.ultsonch.2026.107830. Online ahead of print.

ABSTRACT

Bisphenols are widespread in the environment and can cause harm to aquatic and terrestrial life by acting as an endocrine disruptor, affecting reproduction, growth, and development. Hydrodynamic cavitation and photocatalysis can both be used to remove bisphenols from aquatic bodies, yet the reports on the combination of the two in a single system are scarce. Herein, we studied the removal of five bisphenols from tap water (TW) and real wastewater (WW) effluent at two environmentally relevant concentration levels, 200 ng/L and 1000 ng/L, by means of hydrodynamic cavitation, both independently and in combination with photocatalysis, using a TiO₂-SiO₂ composite catalyst immobilized on Al₂O₃ monoliths. For tap water, inside the short treatment times (15 min or 30 min) the efficiency of removal reached up to 100% for tetramethyl bisphenol F (TMBPF) while only 15% for bisphenol S (BPS). Interestingly, the average total amount of BPAs removed across all treatment combinations was almost the same in case of TW (58.5 ng) and WW (60.4 ng). The current study shows an important advancement in the practical applicability of the two methods for treating polluted water bodies which is applicable to the upcoming implementation of the quaternary treatment in WW treatment plants.

PMID:41936211 | DOI:10.1016/j.ultsonch.2026.107830

Int J Hyg Environ Health. 2026 Apr 4;274:114794. doi: 10.1016/j.ijheh.2026.114794. Online ahead of print.

ABSTRACT

Environmental phenols are endocrine-disrupting chemicals widely used in personal care products. They have been shown to affect the mammary gland, but knowledge about their impact on breastfeeding duration is limited. We aimed to explore associations between maternal phenols exposure during pregnancy and breastfeeding duration. We included 373 mother-infant pairs from the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio, USA) enrolled from 2003 to 2006. We measured urinary concentrations of eight phenols at 16 and 26 weeks of gestation (bisphenol A, triclosan, benzophenone-3, 2,4-/2,5-dichlorophenols, methyl-/propyl-/butyl-paraben) and collected breastfeeding information until mothers reported discontinuation of exclusive and any breastfeeding. We assessed the hazard ratios (HRs) and odds ratios (ORs) of the cessation of breastfeeding in relation to the eight phenols using confounder adjusted Cox proportional hazards and logistic regression models, respectively. In adjusted Cox regression models, each doubling of urinary triclosan concentration was associated with HRs of 1.09 (95% CI: 1.00, 1.18) for any breastfeeding cessation within 6 months, and 1.08 (95% CI: 0.96, 1.21) for cessation between 6 and 12 months, with tertile-categorized analyses suggesting a dose-response relationship for cessation within 6 months. We did not observe consistent associations with breastfeeding duration for the seven other phenols, but each doubling concentrations in triclosan and BP-3 were associated with 18% (95% CI: 3, 35%) and 13% (95% CI: 1, 26%), respectively, higher odds of terminating breastfeeding earlier than intended. Considering the limited sample size and multiple testing, our findings need to be confirmed in larger studies.

PMID:41936220 | DOI:10.1016/j.ijheh.2026.114794

Food Chem. 2026 Apr 1;514:149089. doi: 10.1016/j.foodchem.2026.149089. Online ahead of print.

ABSTRACT

Phenolic endocrine disrupting compounds (PEDCs) are associated with significant health hazards, necessitating the development of highly sensitive analytical detection methodologies‌. This study reported a novel covalent organic framework (DT-COF) by strategically incorporating hydroxyl-rich building blocks into π-conjugated architectures. DT-COF demonstrated enhanced adsorption effect for PEDCs through the multiple hydrogen bond binding and multiple π-π interaction sites. By using DT-COF as a solid phase extraction adsorbent and integrating it with high performance liquid chromatography tandem the mass spectrometry, a robust analytical platform was provided to determine the trace PEDCs in green tea beverages, bottled water, and milk. Under optimized conditions, the method exhibited excellent analytical performance, including a low detection limit (0.018-0.219 ng mL^-1), good recovery rates (86.3-109%), and outstanding reproducibility (RSDs ≤6.6%). This study achieves dual objectives: enabling sensitive detection of PEDCs contaminants while pioneering functional COF material development.

PMID:41936778 | DOI:10.1016/j.foodchem.2026.149089

Environ Pollut. 2026 Apr 3:128050. doi: 10.1016/j.envpol.2026.128050. Online ahead of print.

ABSTRACT

Pharmaceutical pollution is escalating worldwide due to increasing drug consumption and limited removal in conventional wastewater treatment plants. While low concentrations of SSRIs can already disrupt endocrine and behavioural functions in aquatic species, the long-term effects of sediment-associated SSRIs remain largely unexplored. In this study, we examined multigenerational effects of sediment-associated sertraline (SER; 0-15.6 μg/g dry weight sediment) on the polychaete Capitella teleta across three generations (f0-f2), assessing reproductive traits in all generations and behaviour only in f2. In f0, worms exposed to the lowest concentration (0.1 μg/g) produced ∼50% more mature individuals than controls after four weeks, but this stimulatory pattern reversed in f2. At the highest concentration (15.6 μg/g), maturation in f1 was delayed by one week relative to other concentrations. Worms exposed to 0.7 μg/g SER were consistently smaller across all generations, and in f2 they were ∼30% smaller than controls, whereas individuals in 15.6 μg/g were nearly 34% larger than controls. SER exposure delayed the onset of reproduction, particularly at higher concentrations, and caused subtle shifts in brooding intervals. Egg size and number were largely unaffected; however, worms in 15.6 μg/g increased egg production across generations, while those in 0-6.4 μg/g SER showed generational declines. Hatching success (quantified only in f2) decreased by ∼30% at both 6.4 and 15.6 μg/g. Behavioural endpoints in f2 revealed concentration-dependent effects: low SER enhanced negative phototaxis, intermediate concentrations increased burrowing activity, whereas high concentrations impaired burrowing and induced abnormal surface-rolling behaviour. Despite multigenerational exposure, worms did not avoid contaminated sediment in f2, suggesting no behavioural adaptation. Overall, our findings demonstrate that even environmentally relevant levels of sediment-associated SSRIs can elicit repro-toxic, neurotoxic, and multigenerational effects in C. teleta. Such multigenerational impacts in natural systems could alter population dynamics, potentially affecting ecological interactions.

PMID:41936806 | DOI:10.1016/j.envpol.2026.128050

Reprod Toxicol. 2026 Apr 3;143:109238. doi: 10.1016/j.reprotox.2026.109238. Online ahead of print.

ABSTRACT

INTRODUCTION: Hypospadias and undescended testis (UDT) are common genital malformations with multifactorial origins. Endocrine-disrupting chemicals, including pesticides, are suspected contributors, but prior reviews are outdated, and none has mapped evidence for both conditions together.

OBJECTIVE: To map evidence on the association between prenatal pesticide exposure and hypospadias/UDT, with particular attention to underexplored exposures such as pyrethroids and household pesticides, and to identify research gaps.

METHOD: Following PRISMA-ScR guidance, we searched PubMed, Web of Science, Cochrane, and Embase from 2003 to 2024. Eligible items were original human studies and reviews. Study selection and data extraction were performed by two reviewers.

RESULTS: We included 117 articles (62 case-control studies, 7 population-based/cohort/epidemiological studies, 4 meta-analyses, and 44 reviews). Evidence from primary studies was heterogeneous across designs, but several signals recurred: increased risks associated with maternal occupational or residential exposure in agricultural settings; positive associations when exposure was assessed using bioaccumulative matrices (placenta, breast milk, meconium); and limited or null findings with single time-point blood/urine measures. Data on household insecticides use remain scarce, particularly for pyrethroid insecticides. Few studies examined gene-environment interactions.

CONCLUSION: This scoping review highlights suggestive but inconsistent evidence that prenatal pesticide exposure contributes to hypospadias/UDT, with organochlorines (e.g., DDT/DDE, atrazine) most frequently implicated. Key gaps include pyrethroid exposure, prospective designs with improved exposure assessment, and stronger links between human epidemiological findings and existing mechanistic evidence. While causal inference is limited in a scoping review framework, the overall body of evidence supports adopting a precautionary approach to minimizing pesticide exposure during pregnancy.

PMID:41937090 | DOI:10.1016/j.reprotox.2026.109238