Endocrine Disruption

Lipidomic alterations in oysters caused by environmentally relevant exposure to microplastics and estrogenic endocrine disrupting chemicals - February 28, 2026

Ecotoxicology. 2026 Feb 28;35(4):70. doi: 10.1007/s10646-026-03055-2.

NO ABSTRACT

PMID:41762286 | DOI:10.1007/s10646-026-03055-2

Hydrodynamic modulation of microplastic bioaccumulation in edible fish: Integrating biomarker networks, machine learning, and food safety perspectives - February 28, 2026

Food Chem. 2026 Feb 25;509:148610. doi: 10.1016/j.foodchem.2026.148610. Online ahead of print.

ABSTRACT

Microplastic (MP) pollution poses increasing environmental and food safety risks, yet the role of hydrodynamics in MPs bioaccumulation and fish physiology is unclear. This study assessed the effects of 5 μm polystyrene MPs (1000 μg/L) on Ctenopharyngodon idella under static conditions and at water velocities of 1, 3, and 5 body lengths per second (BL/s). Fish exposed to high velocity showed highest MPs bioaccumulation (58.1 ± 10.5 × 10³ μg/kg), and histological damage, including fiber degeneration, necrosis, and hemorrhage. Biomarkers indicated oxidative stress, neurotoxicity, and disrupted energy metabolism, while endocrine and neurochemical disturbances reflected systemic stress and reduced tissue quality. Factorial ANOVA and structural equation modeling revealed independent and synergistic effects of MPs and hydrodynamics on muscle damage. Machine learning identified ATPase, superoxide dismutase, and cholinesterase as key predictive biomarkers (87.5% accuracy). Collectively, these findings challenge static-exposure paradigms in MPs toxicity studies and demonstrate hydrodynamics drive MPs bioaccumulation and effects, requiring ecological risk assessment inclusion.

PMID:41762579 | DOI:10.1016/j.foodchem.2026.148610

Early antidepressant exposure rewrites the script of coping - February 28, 2026

J Hazard Mater. 2026 Feb 23;506:141586. doi: 10.1016/j.jhazmat.2026.141586. Online ahead of print.

ABSTRACT

Exposure to neuropharmaceuticals at early stages of development may affect brain development and elicit long-lasting effects, leading to alterations in stress-coping behaviour, critical for adaptation in ecosystems progressively shaped by anthropogenic influences. Paroxetine (PAR), a selective serotonin reuptake inhibitor antidepressant, has been increasingly detected in water systems worldwide, raising concerns about its impact on biota, as it has been shown to affect fish behaviour. However, the effects of PAR exposure on stress-coping styles, such as the bold-shy scope and personality-linked behavioural responses, remain unexplored. Nevertheless, considering the role of behavioural variability in population adaptability, disruptions to these traits during brain development may have important ecological implications. Thus, this study aimed to assess how zebrafish's early developmental exposure to environmental levels of PAR may affect later-life stress-coping behaviours. To investigate this, zebrafish embryos were exposed during a susceptible developmental window (from 3 to 48 h post-fertilisation, hpf) to 0.04 and 0.4 µg/L PAR. After exposure, embryos were transferred to clean media and allowed to develop until the larval stage (8 days post-fertilisation, dpf) and the juvenile stage (45 dpf). Transient embryonic exposure to PAR disrupted the normal development of coping styles, with early behavioural alterations progressing into more pronounced, phenotype-specific disruptions in behaviour, monoaminergic and endocrine regulations at the juvenile stage.

PMID:41762460 | DOI:10.1016/j.jhazmat.2026.141586

Lipidomic alterations in oysters caused by environmentally relevant exposure to microplastics and estrogenic endocrine disrupting chemicals - February 28, 2026

Ecotoxicology. 2026 Feb 28;35(4):70. doi: 10.1007/s10646-026-03055-2.

NO ABSTRACT

PMID:41762286 | DOI:10.1007/s10646-026-03055-2

In vitro transformation assessment of organophosphate esters (OPEs) via electrochemistry and rat liver S9 and their toxicological evaluation - February 28, 2026

Ecotoxicol Environ Saf. 2026 Feb 26;312:119959. doi: 10.1016/j.ecoenv.2026.119959. Online ahead of print.

ABSTRACT

Organophosphate esters (OPEs) can be biodegraded through phase Ⅰ process in liver by cytochrome P450 enzymes and cause adverse effects to target organs. This study examined the transformation of three OPEs using electrochemistry (EC) and rat liver S9 system to compare the distinctions between the two systems concerning their transformation products (TPs) formed. The toxic effects of OPEs and the primary TPs include endocrine disruption, genotoxicity and dioxin-like potential were further investigated across a range of exposure concentrations that do not induce significant cytotoxicity. OPEs were transformed in both EC and S9 with the degradation degree followed as tris(4-isopropylphenyl) phosphate (T4IPPP)> tris(2-butoxyethyl) phosphate (TBOEP)> tris(1,3-dichloro-2-propyl) phosphate (TDCIPP). Compared with S9 system, the transformation of OPEs in EC method was relatively slower. Bis(butoxyethyl) phosphate (BBOEP), hydroxyethyl phosphate triester (BBOEHEP) and bis(2-butoxyethyl) 2-(3-hydroxybutoxy) ethyl phosphate triester (3-OH-TBOEP) were the most abundant TPs of TBOEP, while bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was the only TPs of TDCIPP detected in EC and S9 system. Concerning the toxic effects, OPEs declined the cell viability significantly in H4ⅡE, A549 and U2OS cells in time- and concentration- specific relationship. However, no significant cytotoxic effect occurred after exposure to the TPs up to 1000 μM. TDCIPP showed significant antagonistic activities against ERα and AR with IC10 value of 42.4 and 0.301 μM, respectively. BBOEHEP and BDCIPP also exhibited ERα agonistic activity and antagonistic AR activity, which was lower than that of their respective parent compounds. Furthermore, OPEs and their TPs caused significant micronucleus formation in the absence or presence of S9 fraction compared to the solvent control. Taken together, TDCIPP pose considerable risks to humans and the environment considering the limited transform capability and strong toxic effects.

PMID:41762593 | DOI:10.1016/j.ecoenv.2026.119959

Melatonin safeguards against butylparaben-induced oxidative stress, DNA damage, microtubule instability, and organelle dysfunction during porcine oocyte maturation - February 28, 2026

J Hazard Mater. 2026 Feb 26;506:141621. doi: 10.1016/j.jhazmat.2026.141621. Online ahead of print.

ABSTRACT

Butylparaben (BP) is widely used in food, beverage containers, personal care products, and cosmetics, resulting in high human exposure. Previous studies reported a potential link between BP and adverse effects on human health, but its effects on female reproduction and the underlying mechanisms remain to be fully elucidated. This study examined the molecular mechanisms of BP-induced female reproductive damage and a potential therapeutic strategy. BP exposure was found to impair cumulus cell expansion, oocyte nuclear maturation, and subsequent embryonic development. BP-exposed oocytes exhibited abnormalities in microtubule structure, stability, and actin-mediated cytoskeleton dynamics. BP exposure also induced cytoplasmic maturation defects by disrupting mitochondria, the endoplasmic reticulum, and lipid metabolism. In addition, BP exposure induces oxidative stress, which interferes with DNA double-strand break repair, causes DNA damage, and ultimately leads to cell death. However, melatonin (MLT) supplementation ameliorated BP-induced meiotic and developmental defects in porcine oocytes. These results suggest that MLT plays a protective role in BP-exposed oocytes by preventing meiotic failure due to impaired nuclear and cytoplasmic maturation. MLT supplementation, therefore, offers a strategy to improve oocyte quality, fertility, and subsequent embryonic development. Our findings regarding the toxicological effects of endocrine disruptors on female reproduction suggest a novel approach for preserving female fertility.

PMID:41762836 | DOI:10.1016/j.jhazmat.2026.141621

Hydrodynamic modulation of microplastic bioaccumulation in edible fish: Integrating biomarker networks, machine learning, and food safety perspectives - February 28, 2026

Food Chem. 2026 Feb 25;509:148610. doi: 10.1016/j.foodchem.2026.148610. Online ahead of print.

ABSTRACT

PMID:41762579 | DOI:10.1016/j.foodchem.2026.148610

Diethyl phthalate-induced oxidative stress, genotoxicity, and thyroid hormone disruption in female Wistar rats - February 28, 2026

Food Chem Toxicol. 2026 Feb 26:116031. doi: 10.1016/j.fct.2026.116031. Online ahead of print.

ABSTRACT

BACKGROUND: Diethyl phthalate (DEP), a common plasticizer in cosmetics and personal care products, is known to induce oxidative stress and endocrine disruption. Its widespread use raises concerns about thyroid toxicity.

OBJECTIVE: This study aimed to evaluate the genotoxic and endocrine effects of subacute DEP exposure on thyroid tissue in female Wistar albino rats using thyroid hormones, oxidative stress markers, DNA damage, and histopathology.

METHODS: Twenty-eight female Wistar albino rats were divided into four groups (n=7): control, 100 mg/kg, 300 mg/kg, and 600 mg/kg DEP. DEP was administered orally for 21 days. DNA damage was assessed by Comet Assay, oxidative stress markers (TAS, TOS, OSI) were measured, and serum TSH, T3, and T4 levels were determined by ELISA. Body weights were monitored, and thyroid tissues were examined histologically.

RESULTS: Compared to the control group, T3 and T4 levels decreased (P<0.05), TSH levels increased (p<0.05), TAS levels decreased (p<0.05), and TOS and OSI levels increased (p<0.05). Comet Assay showed dose-dependent DNA damage (tail DNA%, p<0.05). With higher DEP doses, thyroid tissue histopathology changed significantly.

CONCLUSION: Subacute DEP exposure causes dose-dependent genotoxicity, oxidative stress, and endocrine disruption in thyroid tissue. These findings emphasize the need to limit environmental and human DEP exposure.

PMID:41763288 | DOI:10.1016/j.fct.2026.116031

Chain-length matters: How benzylalkyldimethylammonium quaternary disinfectants disrupt gonadal steroidogenesis via 3beta-hydroxysteroid dehydrogenase inhibition - February 28, 2026

Ecotoxicol Environ Saf. 2026 Feb 27;312:119960. doi: 10.1016/j.ecoenv.2026.119960. Online ahead of print.

ABSTRACT

Benzylalkyldimethylammonium (BAC) quaternary disinfectants are extensively used as antimicrobial agents. However, the specific BACs responsible for inhibition and their structure-activity relationship (SAR) for human 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) and its homolog rat 3β-HSD1, the critical enzyme in gonadal steroidogenesis, remain poorly understood. This study evaluated nine BACs for their inhibitory effects on human 3β-HSD2 and rat 3β-HSD1, determining potency (IC₅₀), inhibition kinetics, cellular impact, and binding interactions via molecular docking and 3D-QSAR. Inhibitory potency (IC₅₀) revealed C18 (11.84 μM) > C16 (15.51 μM) > C14 (25.25 μM) > C12 (30.63 μM) > C10 (56.86 μM) > C1-C8 BACs (no inhibition at 100 μM) against human 3β-HSD2 and C18 (8.23 μM) > C16 (10.74 μM) > C14 (12.21 μM) > C12 (14.38 μM) > C10 (26.62 μM) > C1-C8 BACs (no inhibition at 100 μM) against rat 3β-HSD1. Both enzymes exhibited mixed-type inhibition. Cellular suppression showed that C14, C16, and C18 BACs inhibited progesterone synthesis in human KGN granulosa tumor cells at ≥ 5 μM. Docking and SAR revealed binding at the NAD+ /steroid site via hydrogen bonding, hydrophobic, and van der Waals interactions. Lipophilicity (LogP), steric bulk, Fsp3, and flexibility correlated positively with potency, indicating that longer alkyl chains (≤C18) enhance inhibition. 3D-QSAR confirmed the importance of hydrophobic regions in binding affinity due to long alkyl chain. In conclusion, BACs inhibit gonadal 3β-HSD activity in a chain-length-dependent manner (C10-C18), with lipophilicity as a key determinant. These findings suggest that BAC disinfectants may act as potential endocrine disruptors by interfering with steroidogenesis.

PMID:41762982 | DOI:10.1016/j.ecoenv.2026.119960

Bisphenol A induces IRE1-dominant endoplasmic reticulum stress, apoptosis, and functional impairment in BeWo trophoblast cells - February 28, 2026

Reprod Toxicol. 2026 Feb 26:109208. doi: 10.1016/j.reprotox.2026.109208. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in polycarbonate plastics and epoxy resins, resulting in human exposure primarily through food-contact materials and thermal paper, as well as environmental sources. Studies suggest that BPA has adverse effects on trophoblast cells, which are critical for placental formation, and that the endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may contribute to BPA-induced cellular dysfunction. However, the mechanisms by which BPA affects placental trophoblast function remain incompletely understood. This study aimed to explore the connection between ER stress/UPR signaling and BPA-induced trophoblast disfunction. BeWo cells were stimulated with forskolin to induce a syncytium formation, a hallmark of trophoblast differentiation, and then exposed to different concentrations of BPA. The effect of BPA on differentiation and secretion capacity, viability, and apoptosis of the trophoblast cells was examined comparing the results with data related to ER stress. Our findings provide evidence that ER stress/UPR activation is involved in BPA-induced trophoblast dysfunction and that BPA-induced apoptosis may be linked to ER stress. In conclusion, this study offers mechanistic insights into how BPA impacts trophoblast cells and may help in understanding the pregnancy-related adverse outcomes associated with BPA exposure.

PMID:41763332 | DOI:10.1016/j.reprotox.2026.109208

Per- and polyfluoroalkyl substances (PFAS) and menstrual cycle characteristics in midlife women: the Study of Women's Health Across the Nation - February 28, 2026

Reprod Toxicol. 2026 Feb 26:109207. doi: 10.1016/j.reprotox.2026.109207. Online ahead of print.

ABSTRACT

OBJECTIVE: Evidence suggests exposure to endocrine-disrupting chemicals, including per- and polyfluoroalkyl substances (PFAS), may disrupt ovarian function and influence menstrual bleeding. PFAS have been associated with reproductive aging; however, longitudinal data on PFAS and menstrual cycle characteristics (cycle length, bleeding patterns) are limited.

METHODS: We examined 952 women aged 45-55 years from the Study of Women's Health Across the Nation, with seven PFAS concentrations measured in serum collected in 1999-2000. Menstrual cycle data were collected prospectively using monthly calendars for two years following PFAS measurement. Menstrual cycle length (MCL) was evaluated using linear quantile mixed models at the 25th, 50th, 75th, and 90th percentiles. Bleed length and binary bleeding outcomes (long and heavy) were analyzed using linear and generalized linear mixed models. Models were adjusted for race/ethnicity, education, physical activity, menopause status, smoking status, body mass index, and baseline menstrual characteristics.

RESULTS: Higher perfluorooctane sulfonic acid concentrations were associated with shorter short cycles (MCL at the 25^th percentile) (-0.52 days; 95% CI, -1.09 to 0.05) and longer long cycles (MCL at the 90^th percentile) (2.77 days; 95% CI, 1.96 to 3.58). Perfluorononanoic acid was associated with longer short cycles (0.56 days; 95% CI, 0.06 to 1.05). No PFAS was associated with median MCL. Most PFAS, except 2-(N-methyl-perfluorooctane sulfonamido) acetic acid and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid, were associated with shorter menses and lower odds of long or heavy bleeding.

CONCLUSION: PFAS exposure may be associated with increased menstrual cycle variability and reduced bleeding. Further research in younger cohorts is needed.

PMID:41763333 | DOI:10.1016/j.reprotox.2026.109207

Association between prenatal exposure to per- and polyfluoroalkyl substances and pubertal development in boys and girls in the Spanish INMA cohort - February 28, 2026

Environ Res. 2026 Feb 26:124095. doi: 10.1016/j.envres.2026.124095. Online ahead of print.

ABSTRACT

Exposure to endocrine-disrupting chemicals (EDCs), including per- and polyfluoroalkyl substances (PFAS), has been linked to altered pubertal timing, though epidemiological findings remain inconsistent. This study examined associations between prenatal PFAS exposure and pubertal development in children. Concentrations of perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and perfluorononanoic acid (PFNA) were quantified in maternal plasma collected during the first trimester of pregnancy in the Spanish INMA (Infancia y Medio Ambiente) cohort. Children's pubertal development was assessed longitudinally between ages 7 and 13 using the parent-reported Pubertal Development Scale (PDS), with specific scales for gonadal and adrenal development. Data were available for 492 mother-girls pairs at the 7-9-year follow up and 475 mother-boys pairs at the 11-13-year follow up based on the typical sex-specific timing of puberty. Poisson regression and Bayesian Kernel Machine Regression (BKMR) were used to estimate associations between PFAS (individually and as mixtures, respectively) and the risk of earlier puberty development (PDS stage 1 vs. 2+), adjusting for confounders. Among girls, PFHxS was associated with an increased risk of early adrenarche (Relative Risk [RR]=1.85; 95% confidence interval [CI]: 1.05-3.25), while PFOS was inversely associated with early gonadarche RR=0.61; 95% CI: 0.37-1.00). In boys, PFOS showed a marginal trend toward an increased risk of early overall pubertal onset (RR=1.47; 95% CI: 0.99-2.19). Stratified analyses mainly revealed stronger associations among overweight/obese children. The mixture analysis suggested a positive trend for early adrenal development in both sexes, with significant associations in boys. Although our findings do not provide definitive evidence of a relationship between prenatal PFAS exposure and pubertal timing, they are compatible with the endocrine-disrupting potential of PFAS. The observed patterns, including possible modification by weight status and mixture signals, warrant further research.

PMID:41763473 | DOI:10.1016/j.envres.2026.124095

Freshwater Snails Avoid PFOS But Only At Concentrations Well Above EPA Safe Water Standards - February 28, 2026

Environ Toxicol Chem. 2026 Feb 27:vgag049. doi: 10.1093/etojnl/vgag049. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent synthetic chemicals with known toxicological effects, including endocrine and developmental disruption. Perfluorooctanesulfonic acid (PFOS), one of the most prevalent PFASs, can enter freshwater ecosystems via runoff and effluents, potentially transferring through food webs to humans. Freshwater pulmonate snails (family: Lymnaeidae) occupy a basal trophic position and may act as both PFOS bioindicators and contaminant vectors. We tested whether Stagnicola elodes snails could detect and behaviorally avoid PFOS at environmentally relevant concentrations using a Y-tube choice assay. Snails were given a choice between control water and PFOS solutions ranging from 4 to 2500 ng/L. Behavioral outcomes were classified as movement toward PFOS, toward control water, or no decision. Avoidance behavior was significant at 300 ng/L when excluding non-decision snails, and at 100, 300, and 400 ng/L when including them. These results suggest that S. elodes can detect PFOS within a narrow concentration range, but behavioral responses are modest and at levels above safe drinking water standards (∼4 ng/L), minimizing both their potential as a strong bioindicator species for PFOS contamination and their ability to limit trophic transport.

PMID:41761455 | DOI:10.1093/etojnl/vgag049

Freshwater Snails Avoid PFOS But Only At Concentrations Well Above EPA Safe Water Standards - February 28, 2026

Environ Toxicol Chem. 2026 Feb 27:vgag049. doi: 10.1093/etojnl/vgag049. Online ahead of print.

ABSTRACT

PMID:41761455 | DOI:10.1093/etojnl/vgag049

Association between prenatal exposure to per- and polyfluoroalkyl substances and pubertal development in boys and girls in the Spanish INMA cohort - February 28, 2026

Environ Res. 2026 Feb 26:124095. doi: 10.1016/j.envres.2026.124095. Online ahead of print.

ABSTRACT

PMID:41763473 | DOI:10.1016/j.envres.2026.124095

Per- and polyfluoroalkyl substances (PFAS) and menstrual cycle characteristics in midlife women: the Study of Women's Health Across the Nation - February 28, 2026

Reprod Toxicol. 2026 Feb 26:109207. doi: 10.1016/j.reprotox.2026.109207. Online ahead of print.

ABSTRACT

CONCLUSION: PFAS exposure may be associated with increased menstrual cycle variability and reduced bleeding. Further research in younger cohorts is needed.

PMID:41763333 | DOI:10.1016/j.reprotox.2026.109207

Genetic and Environmental Architecture of Ram Fertility Traits: A Review - February 27, 2026

Genes (Basel). 2026 Feb 9;17(2):210. doi: 10.3390/genes17020210.

ABSTRACT

BACKGROUND/OBJECTIVES: Ram fertility is essential for sheep production, influenced by genetic, physiological, behavioral, and environmental factors. This narrative review synthesizes findings from over 190 peer-reviewed publications to evaluate the phenotypic indicators, genetic architecture, molecular candidates, and management conditions influencing testicular development, semen quality, and reproductive performance in rams.

METHODS: A narrative synthesis of peer-reviewed studies was conducted, integrating findings from quantitative genetics, genome-wide association studies, transcriptomics, and controlled environmental and management experiments. Emphasis was placed on studies evaluating fertility-related traits across breeds, ages, and production systems.

RESULTS: Recent genomic and transcriptomic studies have identified potential biomarkers (e.g., IGF1, IGFALS, FOXO1) and gene networks linked to ram fertility, including semen quality, scrotal circumference, and endocrine regulation. For instance, genome-wide association studies (GWASs) have identified candidate genes such as SLC2A8 and MAPK3, which are associated with spermatogenesis and semen quality. Additionally, Y-linked SNPs such as ZFY16: g.146 C > T have been linked to testicular development. Genetic potential is heavily modulated by environmental constraints. Heat stress emerges as a disruptor of testicular thermoregulation, with recent evidence highlighting the vulnerability of spermatogenesis even in adapted breeds. Management interventions, specifically nutritional supplementation and hormonal modulation via melatonin, are discussed as effective strategies to mitigate environmental impacts.

CONCLUSION: Improving ram fertility will require an approach that prioritizes phenotypic traits supported by candidate genes identified through transcriptomic analyses and GWASs. Integrating these genetic tools together with cost-effective nutritional and hormonal management strategies can further improve semen quality, libido, and testicular traits, thereby enhancing fertility gains while maintaining sheep breed adaptability across production systems.

PMID:41751594 | PMC:PMC12940677 | DOI:10.3390/genes17020210

Comprehensive Analysis of the Placenta-Cortex Transcriptomic Database Reveals a Neuroactive Ligand-Receptor Dysregulation After Prenatal Alcohol Exposure - February 27, 2026

Int J Mol Sci. 2026 Feb 14;27(4):1819. doi: 10.3390/ijms27041819.

ABSTRACT

Neuroplacentology is an emerging field of research supporting that the placenta actively contributes to the fetal brain development through the release of bioactive molecules. Recent angiogenesis-focused data showed that prenatal alcohol exposure (PAE) disrupts inter-organ gene expression between the placenta and fetal cortex. The present study aimed to perform the first comprehensive and untargeted analysis of a murine placenta-cortex transcriptomic database of PAE. Gene lists from a recently NCBI-deposited PAE Placenta-Cortex transcriptomic database were analyzed using g:Profiler for unbiased functional profiling querying Gene Ontology, KEGG, and Reactome databases. Genes intersecting with cell-cell communication terms were submitted to STRING and ShinyGO analyses to identify enriched protein-protein interactions and pathways. Several ligand or receptor candidates were then validated by Western blot. g:Profiler revealed 21 enriched GO functional maps, seven KEGG pathways, and six Reactome pathways, of which 11 were related to cell-to-cell communication. STRING analysis exhibited substantial protein-protein interaction enrichments supporting that proteins belonging to the functional maps and pathways are biologically connected. Notably, 38 ligands or receptors from endocrine families including angiotensinogen, leptin, somatostatin, or PACAP were identified. Western blot analysis of protein candidates showed different validation patterns. In particular, the PACAP receptor family confirmed transcriptomic findings and revealed sex-dependent PAE-impacted expression profiles. The present study indicates that PAE is associated with alterations in the transcriptomic placenta-cortex expression profile, including changes in the expression ratios of several ligands and/or receptors implicated in key physiological pathways such as energy balance, vascular development, and neurogenesis. These transcriptomic associations suggest that altered placenta-fetal brain signaling at the gene expression level may be involved in alcohol-induced neurodevelopmental disorders, highlighting the need for future functional validation studies.

PMID:41751956 | PMC:PMC12940763 | DOI:10.3390/ijms27041819

The Impact of Hyperphosphatemia on Mineral and Bone Metabolism: Implications for Bone and Vascular Health - February 27, 2026

Int J Mol Sci. 2026 Feb 17;27(4):1931. doi: 10.3390/ijms27041931.

ABSTRACT

Phosphorus is an essential mineral involved in bone mineralization, energy metabolism, and cellular signaling, whose serum concentration is tightly regulated by an endocrine network including fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), vitamin D and Klotho. Disruption of this balance, particularly in chronic kidney disease (CKD), leads to hyperphosphatemia, which is strongly associated with bone fragility, vascular calcification, and increased mortality. In CKD, impaired phosphorus homeostasis triggers endocrine dysregulation characterized by elevated PTH and FGF23 levels, Klotho deficiency, and altered vitamin D metabolism, resulting in major skeletal and vascular consequences. Experimental and clinical evidence indicates that phosphorus overload contributes directly to skeletal deterioration and early vascular remodeling, even prior to clinically detectable renal impairment. Moreover, high dietary phosphorus intake under conditions of normal renal function reproduces several molecular and structural alterations typically observed in CKD, supporting a pathogenic role for chronic phosphorus excess. The dietary source of phosphorus has gained increasing relevance, as inorganic phosphate additives exhibit high intestinal bioavailability and impose a greater systemic phosphorus burden. Current management strategies rely on dietary restriction, phosphate binders, modulation of intestinal phosphorus transport and optimization of mineral-regulating hormones, although evidence for improved clinical outcomes remains limited. A deeper understanding of the molecular mechanisms linking phosphorus overload to bone and vascular pathology may facilitate the development of more effective preventive and therapeutic strategies.

PMID:41752068 | PMC:PMC12941187 | DOI:10.3390/ijms27041931

Association of PFAS, Metals, Phthalate and Organophosphate Metabolites with Depression Among U.S. Adults - February 27, 2026

Int J Environ Res Public Health. 2026 Feb 6;23(2):205. doi: 10.3390/ijerph23020205.

ABSTRACT

Depression is a major public health concern, and evidence continues to show that environmental toxicants may contribute to its development. This study evaluated the association between depressive symptoms and per- and polyfluoroalkyl substances (PFAS), heavy metals, phthalates, and organophosphate metabolites using data from NHANES 2017-2018. Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Environmental exposure variables were analyzed using multivariable linear regression and Bayesian Kernel Machine Regression (BKMR). All models adjusted for demographic, socioeconomic, behavioral, and clinical covariates. In multivariable linear regression models adjusted for demographic, socioeconomic, behavioral, and clinical covariates, higher urinary dimethylphosphate concentrations were significantly associated with increased depressive symptom scores (β = 0.15; 95% CI: 0.04, 0.27; p = 0.0098). Mono-(2-ethylhexyl) phthalate (MEHP) was also positively associated with PHQ-9 scores (β = 0.001; 95% CI: 0.0003, 0.0019; p = 0.0043). Because environmental mixtures tend to follow non-linear patterns, BKMR analysis was run. BKMR analyses indicated that organophosphate metabolites exhibited the greatest overall contribution to depressive symptoms (group posterior inclusion probability = 0.7875), with diethylphosphate emerging as the most influential individual exposure within the group (conditional PIP = 0.7211). Exposure-response functions suggested non-linear and threshold relationships for several metabolites. These findings identify specific organophosphate and phthalate metabolites as potential contributors to depressive symptoms and support the importance of evaluating chemical mixtures rather than single exposures. Additional longitudinal studies are needed to clarify temporal relationships and to inform public health efforts aimed at reducing exposure to organophosphate pesticides and endocrine-disrupting chemicals.

PMID:41752287 | PMC:PMC12941221 | DOI:10.3390/ijerph23020205

Environmental Pollution and Its Impact on Kidney Diseases: A Comprehensive Review of Current Evidence - February 27, 2026

Life (Basel). 2026 Feb 8;16(2):291. doi: 10.3390/life16020291.

ABSTRACT

Kidney disease is a growing global public health challenge that accounts for substantial morbidity, premature mortality, and rising healthcare costs. Although diabetes mellitus and hypertension remain the principal clinical risk factors for renal injury, accumulating evidence indicates that environmental pollution represents an independent and globally pervasive contributor to kidney disease burden. Long-term exposure to environmental toxicants, including heavy metals, ambient air pollutants, persistent organic pollutants, and endocrine-disrupting chemicals, has been consistently associated with acute kidney injury, an accelerated decline in renal function, and progression to end-stage kidney disease. The kidney is characterized by a high perfusion rate, specialized tubular transport systems, and a central role in xenobiotic metabolism and excretion, which confer heightened vulnerability to environmental insults. Experimental and epidemiological studies have demonstrated that pollutant exposure across the life course converges on shared pathogenic mechanisms, including oxidative stress, inflammatory signaling, mitochondrial dysfunction, fibrogenesis, and persistent epigenetic alterations. Importantly, environmental toxicants not only initiate renal injury, but they also impair intrinsic repair processes, exacerbating susceptibility to chronic and progressive kidney disease. This Review integrates population-based epidemiological data with experimental mechanistic evidence to define environmental exposures, renal cellular targets, and convergent molecular pathways underlying pollutant-induced nephrotoxicity, and aims to translate this knowledge into actionable strategies for kidney disease prevention, clinical risk stratification, and evidence-informed environmental policy.

PMID:41752927 | PMC:PMC12941669 | DOI:10.3390/life16020291

Adipose Tissue Circadian Dysregulation Beyond BMI: Implications for Cardiometabolic Risk and Cardiovascular Disease - February 27, 2026

Life (Basel). 2026 Feb 10;16(2):305. doi: 10.3390/life16020305.

ABSTRACT

Cardiometabolic and cardiovascular risks are commonly assessed using body mass index (BMI) and static measures of adiposity; however, individuals with similar BMI frequently exhibit markedly different metabolic and cardiovascular outcomes. This heterogeneity reflects not only differences in fat distribution but also variation in adipose tissue function and its temporal regulation. Adipose tissue contains intrinsic circadian clocks that coordinate daily rhythms in lipid storage and mobilization, insulin sensitivity, adipokine secretion, and immune activity in alignment with sleep-wake and feeding-fasting cycles. Circadian misalignment, as occurs with shift work, irregular sleep, or mistimed food intake, disrupts this coordination and promotes adipose tissue dysfunction characterized by impaired rhythmic lipid handling, altered endocrine signaling, inflammation, fibrosis, and oxidative stress. Emerging evidence suggests that circadian dysregulation may differentially affect adipose depots, including visceral, epicardial, and perivascular fat, thereby linking chronodisruption to insulin resistance, endothelial dysfunction, atherosclerosis, heart failure phenotypes, and arrhythmia susceptibility. This narrative review synthesizes human, experimental, and translational studies examining adipose tissue circadian regulation as a functional determinant of cardiometabolic and cardiovascular risk beyond BMI. We also discuss the clinical implications of circadian-informed strategies, including chrononutrition and time-restricted eating, as potential tools to improve risk stratification and cardiometabolic health.

PMID:41752941 | PMC:PMC12941584 | DOI:10.3390/life16020305

Impact of Short-Term Dietary Restriction Combined with Amaranth and Canola Oil Supplementation on Salivary Adipokines in Adults with Obesity - February 27, 2026

Nutrients. 2026 Feb 14;18(4):628. doi: 10.3390/nu18040628.

ABSTRACT

Background: Adipose tissue is a crucial endocrine organ, and obesity, due to its associated chronic inflammation and oxidative stress, disrupts adipokine secretion. These adipokines can be detected not only in blood but also in saliva. Dietary changes are a crucial part of managing obesity, encompassing a balanced diet, increased physical activity, and lifestyle modifications. Moreover, adding functional foods like amaranth and canola oils, recognized for their health benefits, may further improve metabolic and inflammatory health. These products have anti-inflammatory effects and may help reduce the pro-inflammatory activity of adipose tissue, thereby improving systemic and oral health. The study aimed to assess the impact of a 3-week calorie-restricted diet, supplemented with canola or amaranth oil on salivary adipokines, i.e., serpin A12, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor receptor-1 (TNF-R1), pH, and salivary flow in obese patients. Methods: A total of 115 adults with obesity (BMI > 30 kg/m²) were enrolled and placed on a 3-week calorie-restricted diet. The study group (n = 44) received additional supplementation: 21 participants received 20 mL of canola oil daily, and 23 received 20 mL of amaranth oil. The control group (n = 71) followed the same calorie-restricted diet without oil supplementation. Non-stimulated saliva was collected twice, for 20 min each time, before and after the intervention, to evaluate flow rate, pH, and concentrations of serpin A12, PAI-1, and TNF-R1. Concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Results: An increase in saliva flow rate was observed in patients supplemented with amaranth oil (p = 0.0367). Both the amaranth oil and canola oil groups showed a significant rise in salivary pH (p = 0.0425). Across all participants, the 3-week calorie-restricted diet resulted in a reduction in salivary PAI-1 (p = 0.0339), serpin A12 (p = 0.0001), and TNF-R1 (p = 0.0058). Conclusions: The 3-week calorie-restricted diet contributed to a decrease in the concentration of adipokines in saliva. The low-calorie diet, combined with supplementation of amaranth and canola oils, increased salivary flow and resulted in higher pH values, indicating greater alkalinity.

PMID:41754145 | PMC:PMC12943514 | DOI:10.3390/nu18040628

Vascular Destabilization and Pericyte Detachment are Mediated by hIAPP Aggregation in Transgenic Mice - February 27, 2026

bioRxiv [Preprint]. 2026 Feb 22:2026.02.21.707196. doi: 10.64898/2026.02.21.707196.

ABSTRACT

AIMS/HYPOTHESIS: Human islet amyloid polypeptide (hIAPP) deposition is a common feature of type-2 diabetes (T2D). Previous studies have demonstrated hIAPP-mediated endothelial cell (EC) dysfunction and inflammation, but little is known about islet microvascular stability or pericyte function in hIAPP-containing islets. This study investigates how islet endothelial cells and pericytes are influenced by hIAPP aggregation.

METHODS: Bulk RNAseq and qPCR were conducted on hIAPP or vehicle treated MS-1 cells and bead-purified human islet CD31+ cells from donors with or without T2D to determine how islet ECs respond to hIAPP exposure. Confocal imaging of living pancreatic slices obtained from hIAPP transgenic mice was conducted to evaluate the effect of hIAPP deposition on islet pericyte function and vasomotor responses.

RESULTS: hIAPP-treated MS-1 cells and ECs purified from T2D islets demonstrate downregulation of leading-edge genes associated with extracellular matrix and cell adhesion pathways. Pericytes from hIAPP-expressing mouse islets appear detached from underlying endothelial cells, which was associated with impaired vasomotor responses to constrictive or dilatory stimuli.

CONCLUSIONS/INTERPRETATION: hIAPP induces vascular destabilization by downregulating mRNA of key extracellular matrix and cell adhesion molecules in ECs, likely promoting the breakdown of EC-EC and EC-pericyte coupling. hIAPP disrupts EC-pericyte connections, and pericyte detachment ultimately impairs pericytes' ability to modulate capillary diameter without impairing intracellular Ca ²⁺ dynamics. Our data suggest that amyloid deposition compromises EC health and survival by altering islet microvascular morphology, stability, and function. This, in turn, may disrupt islet microvascular stability and exacerbate endocrine cell dysfunction in T2D.

RESEARCH IN CONTEXT: What is already known about this subject?: - hIAPP is cytotoxic to islet endothelial cells and beta cells, and contributes to islet failure in type-2 diabetes (T2D)- hIAPP transgenic mice demonstrate islet capillary dilation, loss of vascular structures, and increased pericyte density- Impaired pericyte anchorage and vascular fragmentation drive diabetes-related vasculopathies in other tissues, like the retina, kidney, and brainWhat is the key question?: - How does the surviving microvasculature in islets respond to hIAPP deposition?What are the new findings?: - Endothelial cells demonstrate transcriptional downregulation of key genes involved in cytoskeleton, ECM, and cell-adhesion maintenance, including Thbs1 , Tln1 , and Plec . - Amyloid deposits disrupt homeostatic interactions between endothelial cells and pericytes.- Amyloid-adjacent islet pericytes are detached from endothelial cells and display impaired ability to modulate capillary diameter.How might this impact on clinical practice in the foreseeable future?: - Therapies targeting endothelial cell-pericyte interactions may restore islet microvascular stability and improve islet function, especially in the context of early T2D.

PMID:41756871 | PMC:PMC12934679 | DOI:10.64898/2026.02.21.707196

Obesity and oxidative stress: potential mechanisms in endometrial disorders - February 27, 2026

Front Endocrinol (Lausanne). 2026 Feb 11;17:1709556. doi: 10.3389/fendo.2026.1709556. eCollection 2026.

ABSTRACT

Obesity is a systemic metabolic disorder that is inducing factor for other diseases such as diabetes mellitus, cardiovascular diseases, malignancies, hepatic dysfunction, renal dysfunction and endometrial diseases. Emerging evidence has shown that Oxidative stress (OS) plays a key mediator in the development of obesity and its complications. Obesity itself can produce OS through several different pathways, including disrupting energy metabolism, interfering with endocrine homeostasis, inducing systemic chronic inflammatory responses and changing gut microbiota. Among the complications induced by obesity, endometrial diseases have been closely related to OS. OS damages molecular phenotype of endometrial cells, induces endometrial apoptosis and affects endometrial angiogenesis, decidualization and receptivity. In this review, we will summarize the relationship among obesity, OS and endometrium, that is, how obesity can induce OS with various pathways, how OS damage endometrial structure and function, and further explore the relationship between OS and obesity-associated endometrial disorders and the potential of using antioxidant strategy as a new therapeutic method.

PMID:41757245 | PMC:PMC12932235 | DOI:10.3389/fendo.2026.1709556

What every dentist needs to know about microplastics and dental materials - February 27, 2026

Gen Dent. 2026 Mar-Apr;74(2):52-56.

ABSTRACT

Microplastics (MPs), defined as plastic particles ranging from 1 μm to 5 mm, have become a growing concern with potentially significant implications for human health. Originating from diverse sources, including consumer products, industrial activities, and biomedical supplies, MPs have been detected in water, food, air, and even human tissues. This review focuses on the potential health risks and sources of MPs, particularly those arising from dental products. Dental products such as toothpastes, toothbrushes, dental floss, resin-based composites, denture base materials, and thermoplastic orthodontic appliances contain or generate MPs through degradation and routine use. Human exposure to MPs occurs via ingestion, inhalation, and dermal contact, with evidence suggesting systemic distribution that affects multiple organ systems, including the cardiovascular, nervous, and endocrine systems. MPs can cross critical biological barriers, leading to neurotoxicity, hormonal disruption, and potential carcinogenesis. The cumulative plastic waste from dental care contributes to environmental pollution. Emerging solutions such as biodegradable materials and improved waste management strategies show promise but require further investigation. This review underscores the need for continued research on MP exposure to mitigate health risks and environmental impact.

PMID:41758632

Association of PFAS, Metals, Phthalate and Organophosphate Metabolites with Depression Among U.S. Adults - February 27, 2026

Int J Environ Res Public Health. 2026 Feb 6;23(2):205. doi: 10.3390/ijerph23020205.

ABSTRACT

PMID:41752287 | PMC:PMC12941221 | DOI:10.3390/ijerph23020205

Maternal Poly (I:C)-Induced Placental Inflammation and Endocrine Dysfunction Are Associated with Disrupted Corticogenesis in Mouse Offspring - February 27, 2026

Brain Sci. 2026 Jan 24;16(2):126. doi: 10.3390/brainsci16020126.

ABSTRACT

BACKGROUND/OBJECTIVES: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking MIA to altered neurodevelopment remain incompletely understood. Increasing evidence highlights the placenta as a critical mediator in shaping fetal brain development through immunological and hormonal regulation. Likewise, disruption of placental regulatory functions upon MIA may therefore represent a mechanistic pathway. Here, we investigated how alterations in placental cytokine profiles, innate immune cell composition, and endocrine outputs relate to neuroinflammation and neurogenesis in the offspring.

METHODS: Pregnant mice at gestational day 12.5 received a single intraperitoneal injection of poly (I:C). Placental macrophages, neutrophils, inflammatory cytokines, and nerve growth factor (NGF) expression were examined 72 h later. Neurodevelopmental outcomes, including microglial activity and neurogenic markers, were evaluated in mouse offspring at postnatal day (P) 1 and 6.

RESULTS: MIA induced a significant accumulation of monocytes and neutrophils in the placenta, which was associated with elevated levels of a broad spectrum of inflammatory mediators, including Th17-biased proinflammatory cytokines, chemokines, and adhesion proteins, in the placenta and amniotic fluid. In contrast, the placenta-derived NGF levels were significantly reduced. MIA induced strong and sustained microglial activation in the fetal and neonatal brain. This inflammatory milieu was accompanied by disrupted cortical neurogenesis, characterized by a marked increase in Ki67+ neuronal progenitor cells (NPCs) in the subventricular zone (SVZ), overproduction of early-born Tbr1+ neurons at P1, later-born Satb2+ neurons at P6.

CONCLUSIONS: Collectively, these findings suggest that heightened Th17 inflammatory signaling, coupled with impaired placental endocrine function, contributes to dysregulated cortical neurogenesis in the offspring.

PMID:41750127 | PMC:PMC12937977 | DOI:10.3390/brainsci16020126

Impacts of Long-Term High-Temperature and Low-Salinity Stress on the Circadian Rhythms of Antioxidant, Immune, and Endocrine Systems in Turbot (Scophthalmus maximus) - February 27, 2026

Antioxidants (Basel). 2026 Feb 17;15(2):257. doi: 10.3390/antiox15020257.

ABSTRACT

Turbot (Scophthalmus maximus) is an economically vital cold-water fish frequently challenged by summer heat and low salinity. However, the temporal response of physiological circadian rhythms to such long-term stress remains underexplored. This study investigated antioxidant, immune, and endocrine rhythms in turbot acclimated to control (16 °C, 30 ppt), high-temperature (23 °C), and low-salinity (10 ppt) conditions for 30 days. Subsequently, time-series sampling was performed every 4 h for 72 consecutive hours. Under optimal conditions, hepatic superoxide dismutase (SOD), serum alanine aminotransferase (ALT), and melatonin exhibited robust 24 h rhythms. Long-term stress disrupted this homeostasis through divergent mechanisms. Low-salinity stress induced "rhythmic remodeling," maintaining balance via phase shifts or novel infradian (48-72 h) oscillations in thyroid hormones (T3, T4) and ALT, without oxidative damage. Conversely, high-temperature stress triggered "rhythmic collapse," characterized by a loss of daily rhythms in SOD and ALT, sustained inflammation indicated by elevated acid phosphatase (ACP), metabolic depression (suppressed T3), and malondialdehyde accumulation. These findings demonstrate that heat stress poses a more destructive threat to circadian integrity than hyposmotic stress. Consequently, the rhythmic dynamics of ACP, ALT, T3, and T4 are identified as critical indicators of stress status, serving as potential biomarkers for screening stress-tolerant strains for selective breeding.

PMID:41750637 | PMC:PMC12937773 | DOI:10.3390/antiox15020257

The Complex Path from Mammary Ductal Hyperplasia to Breast Cancer: Elevated Malignancy Risk in Atypical Forms - February 27, 2026

Biomedicines. 2026 Feb 2;14(2):349. doi: 10.3390/biomedicines14020349.

ABSTRACT

BACKGROUND: Mammary ductal hyperplasia represents a spectrum of benign proliferative breast lesions, some of which pose elevated risks for malignant transformation into ductal carcinoma in situ and invasive breast cancer. This narrative review explores why only specific types, particularly those with atypia, exhibit higher progression potential, synthesizing epidemiologic, histopathologic, molecular, and environmental insights.

METHODS: We reviewed key literature from databases, including PubMed, focusing on classification, risk stratification, genetic/epigenetic mechanisms, tumor microenvironment dynamics, and modifiable factors influencing progression.

RESULTS: Benign breast lesions are categorized into non-proliferative, proliferative without atypia, and proliferative with atypia, such as atypical ductal hyperplasia and atypical lobular hyperplasia. Atypia represents a morphologic continuum toward low-grade ductal carcinoma in situ, driven by genetic alterations, epigenetic reprogramming, and changes in the tumor microenvironment, including stromal remodeling, immune infiltration, hypoxia-induced angiogenesis, and extracellular matrix degradation. Dietary factors, such as high-fat intake and obesity, exacerbate progression through inflammation, insulin resistance, and adipokine imbalance, while environmental toxins, including endocrine disruptors, pesticides, and ionizing radiation, amplify genomic instability.

CONCLUSIONS: Understanding differential risks and mechanisms underscores the need for stratified surveillance, biomarker-driven interventions, and lifestyle modifications to mitigate progression. Future research should prioritize molecular profiling for personalized prevention in high-risk hyperplasia.

PMID:41751248 | PMC:PMC12937821 | DOI:10.3390/biomedicines14020349

Evaluation of Cat Exposure to Bisphenol A (BPA) Using Hair Sample Analysis - February 27, 2026

Animals (Basel). 2026 Feb 12;16(4):567. doi: 10.3390/ani16040567.

ABSTRACT

Bisphenol A (BPA) is a synthetic organic compound commonly used as a plasticiser in the industry. It pollutes the environment, harms human and animal organisms, and exhibits endocrine-disrupting properties. Companion animals, living in proximity to humans, are highly exposed to BPA. However, knowledge of cat exposure to this compound is extremely scarce. In the present study, BPA levels were analysed for the first time in cat hair using liquid chromatography-triple quadrupole mass spectrometry. BPA concentrations ranged from below the limit of detection to 955.4 pg/mg, with a mean (±standard deviation) of 67.98 ± 145.2 pg/mg and a median of 27.3 pg/mg. Higher levels of BPA have been found in the strictly indoor cats (mean 79.45 ± 162.2 pg/mg, median 35.3 pg/mg) than in cats with outdoor access (mean 25.93 ± 8.07 pg/mg, median 24.4 pg/mg). Some differences in BPA levels have also been noted depending on age and body condition scores. The results show that cats are exposed to BPA to a considerable extent, and the levels of this compound in hair may depend on many factors. It can be assumed that BPA may negatively affect cat health, but due to limited knowledge of BPA metabolism in cats and its harmful effects in this species, many aspects of these issues require further comprehensive studies.

PMID:41751028 | PMC:PMC12937472 | DOI:10.3390/ani16040567

Health impacts of micro- and nanoplastics in humans: systematic review of in vivo evidence - February 27, 2026

Environ Health. 2026 Feb 27. doi: 10.1186/s12940-026-01282-y. Online ahead of print.

ABSTRACT

BACKGROUND: Microplastics and nanoplastics (MNPs) are pervasive environmental contaminants with potential human health implications. Although laboratory models implicate MNPs in oxidative stress, inflammation, and endocrine disruption, a comprehensive synthesis of direct in vivo human evidence is lacking. We aimed to systematically review studies measuring MNPs in living human subjects and summarise associated health findings.

METHODS: We systematically searched PubMed, Web of Science, Scopus, Cochrane and Embase through 26 December 2024. Two investigators independently screened and selected original research articles that quantified MNPs in biological samples from living humans. We excluded animal, in vitro, cell-line, and injection-based studies, as well as reports on non-plastic micro- and nanoparticles. Data extraction, performed in duplicate, included study design, participant characteristics, detection methods, polymer types, and reported health outcomes. Methodological quality was appraised using Risk Of Bias in Non-Randomized Studies-of Exposures (ROBINS-E). The primary outcome was the presence and burden of MNPs; secondary outcomes were clinical or biomarker associations. No metaanalysis was performed due to heterogeneity.

RESULTS: From 5 522 records, 25 studies met inclusion. Studies employed pyrolysis-gas chromatography/mass spectrometry (n = 9), Raman spectroscopy (n = 8), infrared spectroscopy (n = 7), and Fourier-transform infrared spectroscopy (n = 3), often combined with microscopy for MNP detection. Predominant polymers were polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, and polystyrene. In cardiovascular research (5 studies; n = 454), higher thrombus and plasma MNP burdens correlated with inflammatory markers and adverse cardiac events. Reproductive research (seven studies; n = 327) linked semen and tissue MNPs to reduced sperm quality and accumulation in tumor and placental samples. Gastrointestinal research (9 studies; n = 537) associated fecal MNPs with liver enzyme elevations and gut dysbiosis. Respiratory (3 studies; n = 171) and ocular (1 study; n = 49) research detected MNPs in airway fluids and vitreous humor respectively, with links to airway inflammation and increased intraocular pressure. ROBINS-E assessments indicated moderate to high risk of confounding and exposure-measurement bias; consistency across detection modalities was limited.

CONCLUSION: Human in vivo evidence confirms that MNPs accumulate in multiple organ systems and are associated with inflammation and functional impairment. Methodological heterogeneity and bias constrain causal inference. Prospective cohort studies with rigorous exposure assessment and confounder control are needed to advance understanding and guide policy.

PMID:41761215 | DOI:10.1186/s12940-026-01282-y

LC-MS/MS for Simultaneous Determination and Isomer Separation of 12 Glucocorticoid Residues in Multiple Aquatic Foods - February 27, 2026

Foods. 2026 Feb 11;15(4):652. doi: 10.3390/foods15040652.

ABSTRACT

Glucocorticoid (GC) residues present in aquatic products raise food safety concerns, as their chronic dietary intake may pose potential risks of endocrine and metabolic disruption. For the first time, a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated herein for the simultaneous determination of 12 GCs residues, including critical isomeric pairs and acetate ester derivatives, in a variety of aquatic foods, employing deuterated isotopic internal standards. Key optimizations included using a pentafluorophenyl column for effective isomer separation, a synergistic extraction system for high recovery, and QuEChERS purification to mitigate matrix effects. The method exhibited excellent linearity (r² > 0.996) and high accuracy (recoveries 97.3-99.3%), and the intra- and inter-day precision values were below 3% in five representative aquatic matrices, with a limit of detection (LOD) and a limit of quantification (LOQ) of 0.5 μg/kg and 0.75 μg/kg, respectively. Animal experiments confirmed the in vivo retention of acetate derivatives, justifying their inclusion in monitoring. Real sample analysis of 18 market samples revealed the presence of cortisone and hydrocortisone in 17 samples. This represents the first reported LC-MS/MS method that provides a sensitive, reliable tool for regulatory monitoring of GC residues in diverse aquatic products, thereby supporting food safety assurance.

PMID:41750844 | PMC:PMC12940018 | DOI:10.3390/foods15040652

Health impacts of micro- and nanoplastics in humans: systematic review of in vivo evidence - February 27, 2026

Environ Health. 2026 Feb 27. doi: 10.1186/s12940-026-01282-y. Online ahead of print.

ABSTRACT

PMID:41761215 | DOI:10.1186/s12940-026-01282-y

Neurovascular Impairment in Type 2 Diabetes Mellitus: The Role of Adipocyte-Derived Exosomes - February 27, 2026

Biomolecules. 2026 Feb 3;16(2):233. doi: 10.3390/biom16020233.

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a major metabolic disorder characterized by chronic hyperglycemia with far-reaching morbidities. Among these, diabetes-related cerebrovascular complications such as ischemic and hemorrhagic stroke, cerebral blood vessel disease, and vascular dementia are significant contributors to morbidity and mortality. Adipose tissue is a metabolically active endocrine organ that becomes dysfunctional in T2DM and communicates with distant tissues via secreted factors, including extracellular vesicles such as exosomes (EXs), phospholipid bilayer-enclosed nanosized particles. These adipocyte-derived exosomes (Ad-EXs) carry bioactive cargo, including lipids, proteins, and microRNAs that influence the function of distant organs, including the brain. Evidence indicates that Ad-EXs in T2DM are a significant risk factor for cerebrovascular complications via neurovascular impairment either directly through the adipose tissue-brain axis or indirectly by other organs. This review provides an overview of current knowledge on how Ad-EXs from different adipocyte populations contribute to cerebrovascular complications through oxidative stress, blood-brain barrier disruption, neuroinflammation, and mitochondrial dysfunction. Particular emphasis is placed on recent findings and gaps in knowledge linking diabetic Ad-EXs with brain microvascular endothelial cells that mediate neurovascular crosstalk, contributing to stroke susceptibility and cognitive decline. We also discuss the potential of Ad-EXs as biomarkers and therapeutic targets for cerebrovascular complications of T2DM.

PMID:41750303 | PMC:PMC12937626 | DOI:10.3390/biom16020233

Mas Knockout Mice Present Altered Behavioral and Neuroendocrine Coping Responses to Chronic Unpredictable Stress - February 27, 2026

Mol Neurobiol. 2026 Feb 27;63(1):474. doi: 10.1007/s12035-026-05747-6.

ABSTRACT

Stress is defined as a disruption of homeostasis that elicits adaptive responses aimed at restoring physiological balance. However, when stress becomes chronic or overwhelming, maladaptive changes may occur, contributing to endocrine, behavioral, and neuropsychiatric dysfunctions. Beyond the classical neuroendocrine axes, such as the sympatho-adrenomedullary and hypothalamic-pituitary-adrenal (HPA) axes, the renin-angiotensin system has also being implicated in stress modulation. Previous studies have shown that angiotensin-(1-7), acting through its receptor Mas, exerts a modulatory effect on the stress response, attenuating anxiety- and depression-like behaviors induced by various stressors. Here we investigated the impact of genetic deletion of Mas on the consequences of chronic unpredictable stress (CUS) exposure. Over 21 consecutive days, mice were subjected to random stressors, after which endocrine, behavioral and neurochemical assessments were performed. Mas knockout (KO) mice exposed to CUS exhibited significantly elevated corticosterone and blood glucose levels compared to stressed wild-type mice. In behavioral tests, stressed Mas KO mice displayed the highest immobility times in the forced swimming test, indicating enhanced depressive-like behavior. Anxiety-like behavior was also heightened in Mas KO mice, as evidenced by a significant reduction in the percentage of time spent in the open arms of the elevated plus maze test. Neurochemical analysis revealed a marked reduction in brain-derived neurotrophic factor (BDNF) levels in key brain regions of stressed Mas KO animals. Together, these findings suggest that Mas plays a critical role in the neurobiology of stress, since its absence exacerbates HPA axis hyperactivity, depression- and anxiety-like behaviors, as well as BDNF reduction. Overall, these results highlight the potential neuroprotective role of Mas in stress-related disorders.

PMID:41760815 | PMC:PMC12948773 | DOI:10.1007/s12035-026-05747-6

Assessment of Gold-Mediated Male Reproductive Dysfunction in Male WISTAR Rats Through Sperm Analysis and Testosterone Measurement - February 27, 2026

J Appl Toxicol. 2026 Feb 26. doi: 10.1002/jat.70129. Online ahead of print.

ABSTRACT

Gold has been used for centuries in both ornamental and medicinal contexts. More recently, gold compounds, containing ions or nanoparticles, have attracted attention for their anti-inflammatory, anticancer, and diagnostic applications. Therefore, concerns about systemic toxicity and biodistribution have prompted investigations into the biological effects of gold in animal models and humans. In the present study, we explored the impacts of a gold solution, used in chrysotherapy, on the reproductive function of male Wistar rats. Seven chronic intraperitoneal injections of sodium 3-aurothio-2-hydroxypropane-1-sulfonate at 30% of gold (allochrysine) were administered to adult male Wistar rats over a period of 2 weeks. The control rats received 0.9% NaCl solution. Our results showed that gold has no notable effect on the absolute weight of reproductive organs (testicles, epididymides, seminal vesicles, and the two caudae of the epididymides) and of nonreproductive organs (liver and brain) excepting the kidneys. The assessment of the fertility parameters showed a significant decline in the motility and viability of sperm cells. A slight reduction in the sperm density, and many malformations affecting the spermatozoa were detected, and the testosterone levels in rats' blood were also significantly diminished. Our study showed that administration of gold solution reduced sperm parameters and was a disruptive agent for the endocrine function of testicles. The oxidative stress generation, attributed to this heavy metal, led to a significant hypertrophy of the kidneys probably after inflammation. Thus, gold existing in different medical treatments could be classified as an endocrine disruptor and could be a detrimental factor of male fertility.

PMID:41749514 | DOI:10.1002/jat.70129

What every dentist needs to know about microplastics and dental materials - February 27, 2026

Gen Dent. 2026 Mar-Apr;74(2):52-56.

ABSTRACT

PMID:41758632

Anthropogenic Underwater Noise Induces Anxiety-like Behavior in Zebrafish - February 27, 2026

Animals (Basel). 2026 Feb 9;16(4):536. doi: 10.3390/ani16040536.

ABSTRACT

Underwater noise pollution, driven by human activities, is an emerging environmental concern, yet its effects on fish behavior and physiology remain poorly understood. As a vertebrate model with conserved stress pathways, zebrafish (Danio rerio) is well-suited for investigating the mechanistic basis of such impacts. We hypothesized that daytime and nighttime noise exposure would differentially induce anxiety-like behavior and associated neuroendocrine disruptions in zebrafish, with effects varying by sex. To evaluate this hypothesis, adult zebrafish were exposed to anthropogenic noise (100-1000 Hz, 130 dB) for seven days, specifically during daytime (08:00-20:00) and nighttime (20:00-08:00) periods. Behavioral assays revealed that noise exposure delayed the first entry of females into the top zone during daytime, while both sexes exhibited prolonged bottom-dwelling and reduced exploratory behavior under nighttime noise. Physiological analyses showed elevated plasma cortisol levels in females, accompanied by up-regulated HPI-axis genes, whereas males displayed a non-significant cortisol increase. Neurotransmitter profiling indicated a sex-specific response to nighttime noise: In females, brain 5-hydroxytryptamine (5-HT) showed a non-significant increasing trend, whereas in males it was significantly elevated, while dopamine (DA) decreased in both sexes. Gene expression analysis further revealed disruptions in 5-HT and DA pathways. These findings demonstrate that underwater noise induces anxiety-like behavior in zebrafish by dysregulating endocrine and neurotransmitter systems, with nighttime noise exhibiting more pronounced effects, suggesting that chronic exposure to anthropogenic noise may impair natural behavior and stress regulation in aquatic species, particularly during nighttime periods.

PMID:41750998 | PMC:PMC12937299 | DOI:10.3390/ani16040536

Mycotoxin Alternariol Induces Ca<sup>2+</sup> Dysregulation and Cell Death in Astrocytes: Mechanistic Toxicological Insights - February 26, 2026

J Appl Toxicol. 2026 Feb 26. doi: 10.1002/jat.70054. Online ahead of print.

ABSTRACT

Alternariol (AOH) is a low-molecular-weight mycotoxin produced by Alternaria species, frequently found in cereal grains, tomatoes, and processed foods. While its genotoxic and endocrine-disrupting effects are well established, emerging studies suggest a neurotoxic potential that remains poorly understood. Astrocytes-key regulators of neuronal support and calcium (Ca²⁺) balance in the central nervous system (CNS)-are an underexplored target of AOH toxicity. Here, we investigated the effects of AOH on Ca²⁺ signaling and viability in human astrocytes (Gibco Human Astrocyte, GHA cells). AOH exposure (25-125 μM) caused a concentration-dependent rise in cytosolic Ca²⁺ concentrations ([Ca²⁺]ᵢ) and induced significant cytotoxicity. These effects were reversed by the intracellular Ca²⁺ chelator BAPTA-AM, suggesting a Ca²⁺-dependent mechanism. Mechanistically, AOH mobilized Ca²⁺ from the endoplasmic reticulum (ER), as shown by thapsigargin blockade, and facilitated extracellular influx via store-operated calcium entry (SOCE), inhibited by 2-APB (a SOCE inhibitor) and GF109203X (a protein kinase C, PKC inhibitor). Notably, inhibition of phospholipase C (PLC) by U73122 completely abolished the Ca²⁺ rise, implicating the PLC-ER axis as a key upstream trigger. Together, our findings reveal a novel Ca²⁺-dependent mechanism by which AOH disrupts astrocyte homeostasis, providing new insights into its neurotoxic potential and highlighting Ca²⁺ signaling as a potential therapeutic target in glial toxicology.

PMID:41744135 | DOI:10.1002/jat.70054

Construction of an Adverse Outcome Pathway Framework for Glyphosate-Induced Female Reproductive Toxicity Based on Toxicity Pathways - February 26, 2026

Environ Health (Wash). 2025 Oct 3;4(2):173-188. doi: 10.1021/envhealth.5c00184. eCollection 2026 Feb 20.

ABSTRACT

Glyphosate (GLY), the most widely used herbicide globally, is pervasive in the environment and has been detected in human tissues. Evidence from in vitro and in vivo studies suggests that GLY and its commercial formulations, glyphosate-based herbicides (GBHs), disrupt normal endocrine function, adversely affecting reproduction. This review synthesizes the current knowledge on GLY/GBHs-induced female reproductive toxicity, elucidating mechanisms across molecular, cellular, tissue, organ, and individual/population levels. Using the adverse outcome pathway (AOP) framework, we identify three key molecular initiating events (MIEs): (1) activation of estrogen receptor α (ERα), (2) inhibition of aromatase activity, and (3) disruption of mitochondrial electron transport chain complexes. These MIEs trigger key events (KEs) such as oxidative stress, DNA damage, mitochondrial dysfunction, and epigenetic modifications, leading to cell death. At the tissue/organ level, these changes cause hormonal homeostasis imbalance, impaired oocyte maturation, ovulatory dysfunction, ovarian reserve depletion, and abnormal endometrial hyperplasia, culminating in clinical conditions such as premature ovarian insufficiency and endometrial cancer. By constructing an AOP network, this review establishes causal relationships across biological levels, providing a theoretical basis for health risk assessment and environmental management of GLY. The AOP framework enhances our understanding of GLY-induced female reproductive toxicity and identifies potential biomarkers and intervention targets, offering critical insights for regulatory decision-making and public health protection.

PMID:41743805 | PMC:PMC12930319 | DOI:10.1021/envhealth.5c00184

Atrophic Skeletal Muscle-Derived Extracellular Vesicles Transfer miR-125a-5p to Inhibit Bone Formation in Osteoporosis during Aging - February 26, 2026

Adv Sci (Weinh). 2026 Feb 26:e15362. doi: 10.1002/advs.202515362. Online ahead of print.

ABSTRACT

Understanding how skeletal muscle influences bone formation is essential for uncovering the mechanisms of muscle-bone communication and developing therapies for osteoporosis. Here, we demonstrate that extracellular vesicles (EVs) derived from atrophic skeletal muscle (Aged-SKM-EVs) inhibit bone formation during aging. Utilizing a muscle-specific EV tracking transgenic mouse model, we found that Aged-SKM-EVs were significantly increased and taken up by osteoblasts in bone during aging. Notably, pharmacological blockade of muscle EV generation via a skeletal muscle-targeted delivery of GW4869 significantly restored osteoblast activity and alleviated bone loss in aged mice. Functional studies revealed that Aged-SKM-EVs suppressed bone formation and inhibited osteogenic differentiation both in vivo and in vitro. Mechanistically, we identified miR-125a-5p as a key cargo enriched in EVs from sarcopenic patients and aged mice. Muscle-specific overexpression of miR-125a-5p inhibited osteogenesis and exacerbated muscle atrophy and bone loss, whereas silencing miR-125a-5p in skeletal muscle effectively reversed these effects. Further investigation demonstrated that miR-125a-5p inhibits osteogenic differentiation by directly targeting Sirt7 in preosteoblasts, thereby disrupting SIRT7-mediated histone deacetylation at the Sp7 promoter and suppressing Sp7 transcription. Our findings reveal a novel endocrine pathway from muscle to bone mediated by EV-associated miRNA and highlight miR-125a-5p as a promising therapeutic target for sarcopenia-related osteoporosis.

PMID:41747076 | DOI:10.1002/advs.202515362

Fructose-induced prediabetes causes persistent DNA methylation changes in white adipose tissue despite metabolic normalization - February 26, 2026

Mol Cell Endocrinol. 2026 Feb 24;616:112772. doi: 10.1016/j.mce.2026.112772. Online ahead of print.

ABSTRACT

BACKGROUND: White adipose tissue (WAT) is a key endocrine organ regulating lipid and glucose homeostasis. Early metabolic disturbances may disrupt its endocrine function through epigenetic mechanisms; however, how DNA methylation contributes to prediabetes and its reversal remains largely unexplored.

OBJECTIVE: To characterize genome-wide DNA methylation changes in visceral WAT from prediabetic rats and after dietary normalization.

METHODS: Male rats were fed a standard diet for 70 days and divided into 3 groups: Control (C) received tap water, Fructose (F) consumed a 10% fructose solution, and FC drank a 10% fructose solution for 21 days followed by tap water for 49 days. Plasma parameters were measured and Whole Genome Bisulfite Sequencing was performed on visceral WAT to identify differential CpG methylation, followed by pathway enrichment and network analyses. RT-qPCR was used to evaluate gene expression.

RESULTS: Fructose intake induced a prediabetic phenotype, which was reversed by dietary normalization. In visceral WAT, 1151 differentially methylated CpG sites were identified and 330 genes enriched in oxidative phosphorylation and thermogenesis, key regulators of adipocyte endocrine and mitochondrial function. A stringent analysis showed a subset of CpG sites associated with Kdm4c, Ces1f, and Uxs1, whose expression was modified, suggesting functional implications for endocrine regulation of adipocyte metabolism. Notably, several methylation alterations persisted despite metabolic recovery, indicating incomplete epigenetic reversal.

CONCLUSIONS: Fructose-induced prediabetes produces DNA methylation changes in visceral white adipose tissue. Despite normalization of plasma parameters in the FC group, several epigenetic alterations persisted, highlighting their potential role in early metabolic disturbances leading to T2D.

PMID:41748061 | DOI:10.1016/j.mce.2026.112772

ATPase N-ethylmaleimide-sensitive factor mediated calcium dependent fusion pore closure and endocytosis - February 26, 2026

Commun Biol. 2026 Feb 26. doi: 10.1038/s42003-026-09743-3. Online ahead of print.

ABSTRACT

For a long time, it remained an unresolved question how the fusion pore is regulated to close after fusion occurs during kiss-and-run. Our study focuses on the physiological function of NSF in modulating single vesicle fusion events in live cells, using whole-cell capacitance recording coupled with live-cell confocal imaging. Our results demonstrates that in both male Sprague-Dawley rat adrenal chromaffin endocrine cells and dorsal root ganglion neurons, inhibiting or diminishing the ATPase activity of NSF significantly impedes fusion pore closure, inhibits various forms of endocytosis, and disrupts the replenishment of readily releasable pool. Interestingly, NSF is exclusively required for calcium-dependent exo-endocytosis but not for the calcium-independent process. In response to calcium influx, NSF disassembles the trans-SNARE complex intermediate via its ATPase activity, which regulates fusion pore closure and subsequently mediates slow, fast, and overshoot endocytosis. Our findings revealed a key mechanism for fusion pore regulation in calcium-evoked exo-endocytosis coupling.

PMID:41748728 | DOI:10.1038/s42003-026-09743-3

A helical peptide antagonist of the human growth hormone receptor - February 26, 2026

Endocrinology. 2026 Feb 26:bqag022. doi: 10.1210/endocr/bqag022. Online ahead of print.

ABSTRACT

The binding of human growth hormone (hGH) to the human growth hormone receptor (hGHR) is a key endocrinological process that controls critical aspects of cell growth, proliferation and differentiation. Mechanistically, this sequential, asymmetric binding event involves the interaction between a single hGH molecule and distinct sites (site 1 and site 2) on the extracellular domain of a preformed hGHR homodimer. Our group recently identified S1H, a rationally-designed peptide sequence mimetic of the hGH site 1-binding helix (residues 36-51) that disrupts the hGH-hGHR interaction and inhibits hGH-mediated phosphorylation of signal transducer and activator of transcription 5 (STAT5) in hGHR-positive cell lines. Structure-activity relationship studies revealed a positive correlation between helical propensity and inhibitory potency of the S1H peptide, prompting the design of structurally "stabilized" S1H variants (SS1H) with improved biological activity. In this study, we employed a chemical strategy, termed hydrocarbon stapling, to generate a series of SS1H peptides that proved to be more helical, proteolytically stable and biologically active compared to linear (unstructured) S1H. Notably, one SS1H derivative (SS1HB) inhibited hGH-induced STAT5 phosphorylation in hGHR-positive human bladder cancer cells more effectively than pegvisomant, the only hGHR antagonist currently approved by the FDA. Collectively, our results demonstrate that hydrocarbon stapling improves the antagonistic effects of S1H peptides and elevates their potential as chemical probes to study the molecular mechanisms of hGH signaling. It is also anticipated that SS1H peptides will serve as potent lead compounds for developing next-generation therapeutics designed to treat endocrine disorders that manifest along the hGH-hGHR signaling axis.

PMID:41742787 | DOI:10.1210/endocr/bqag022

Reproductive Toxicity of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer: A Case Report with a Literature Review - February 26, 2026

Diseases. 2026 Jan 30;14(2):51. doi: 10.3390/diseases14020051.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive malignancy that disproportionately affects young women. The integration of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in both early-stage and metastatic TNBC, shifting attention toward long-term survivorship issues, particularly endocrine function and fertility. However, the reproductive safety profile of ICIs remains insufficiently characterized. This narrative review synthesizes current preclinical and clinical evidence on ICI-associated reproductive toxicity, focusing on both direct immune-mediated gonadal injury and indirect disruption of the hypothalamic-pituitary-gonadal axis. Experimental models consistently demonstrate immune cell infiltration of ovarian and testicular tissue, cytokine-driven inflammatory cascades, follicular atresia, impaired spermatogenesis, and altered steroidogenesis following PD-1/PD-L1 and CTLA-4 blockade. Emerging clinical data report cases of immune-related orchitis, azoospermia, testosterone deficiency, diminished ovarian reserve, and premature ovarian insufficiency. Secondary hypogonadism due to immune-mediated hypophysitis represents an additional and frequently underdiagnosed mechanism. We further discuss the oncofertility challenges faced by young patients with TNBC treated with chemoimmunotherapy, emphasizing the uncertainty of fertility risk stratification and the importance of early fertility counseling and individualized fertility preservation strategies. To illustrate the potential clinical impact, we present the case of a 34-year-old nulliparous woman who developed premature ovarian insufficiency two years after neoadjuvant chemoimmunotherapy including atezolizumab, despite ovarian suppression. In conclusion, while ICIs have transformed the therapeutic landscape of TNBC, their potential long-term impact on reproductive and endocrine health represents a clinically significant concern. A precautionary, multidisciplinary oncofertility approach and prospective clinical registries are essential to define the true incidence and mechanisms of ICI-associated reproductive toxicity.

PMID:41745089 | PMC:PMC12939086 | DOI:10.3390/diseases14020051

The Collaborative Collapse: Bile Acid Dysmetabolism as a Central Pathogenic Driver in Canine and Feline Multi-Systemic Disorders-From Mechanisms to Precision Therapeutics - February 26, 2026

Vet Sci. 2026 Feb 12;13(2):182. doi: 10.3390/vetsci13020182.

ABSTRACT

Veterinary metabolomics has redefined bile acids (BAs) from simple digestive surfactants to systemic endocrine signals within a microbial-host metabolic axis. This review aims to evaluate how BA dysmetabolism acts as a central pathogenic factor in canine and feline disease. We analyze the BA pool's integrity, which depends on a specialized functional guild, primarily Peptacetobacter hiranonis, responsible for 7α-dehydroxylation. We delineate two principal pathological profiles: (1) microbial collapse, characterized by secondary bile acid (SBA) depletion and compromised farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) signaling, which exacerbates inflammation in chronic enteropathy (CE), protein-losing enteropathy (PLE), and exocrine pancreatic insufficiency (EPI); and (2) hepato-biliary spillover, wherein host-induced dysfunction results in primary bile acid (PBA) excess. Recent data have linked these disruptions to skeletal health, feline renal fibrosis, cardiac remodeling in myxomatous mitral valve disease (MMVD), and neuroinflammation in epilepsy and hepatic encephalopathy. The discovery of microbially conjugated bile acids (MCBAs) and microbial extracellular vesicles (MEVs) reveals highly specific, vesicle-mediated communication pathways impacting systemic health. Diagnostic protocols should prioritize functional profiling, including the dysbiosis index (DI), serum conjugated BA analysis, and SBA/PBA ratios. Clinical management is moving beyond empirical fecal microbiota transplantation (FMT), towards precision synthetic microbial consortia (SynComs), neuroprotective BAs like tauroursodeoxycholic acid (TUDCA), and molecular postbiotics to restore the collaborative metabolome.

PMID:41745976 | PMC:PMC12944954 | DOI:10.3390/vetsci13020182

Probiotics as Microbiome Modulators in Male Infertility: Rethinking Dysbiosis Across the Gut-Testis Axis - February 26, 2026

J Pers Med. 2026 Feb 6;16(2):99. doi: 10.3390/jpm16020099.

ABSTRACT

Male infertility contributes substantially to couple infertility, and a large proportion of cases remain idiopathic. Dysbiosis within the gut, seminal, and urinary microbiomes has been associated with impaired semen parameters, reproductive tract inflammation, and oxidative stress. This narrative review, informed by a structured literature search, summarizes current evidence for the gut-testis axis and the androbactome in male infertility and discusses mechanistic pathways linking microbial imbalance to sperm dysfunction. Proposed mechanisms include immune activation, increased oxidative stress, endocrine and metabolic perturbations, and disruption of epithelial barriers, including the blood-testis barrier. Early clinical trials report that selected probiotic or synbiotic formulations may be associated with improvements in one or more World Health Organization (WHO) semen parameters and with reductions in oxidative or inflammatory biomarkers (surrogate laboratory endpoints; pregnancy and live-birth outcomes are rarely reported and remain unproven) in selected populations, such as idiopathic infertility and the post-varicocelectomy setting. Given patient heterogeneity, a personalized approach requires prespecified clinical phenotypes and measurable monitoring targets, rather than indiscriminate supplementation. At present, probiotics should be considered an adjunct rather than a stand-alone therapy. Well-designed, contamination-aware microbiome studies and adequately powered randomized trials with clinically meaningful endpoints, including pregnancy and live birth, are required before routine clinical implementation. This synthesis is intended to support personalized counseling and trial design by clarifying candidate phenotypes, appropriate monitoring endpoints, and realistic limitations of current evidence.

PMID:41745391 | PMC:PMC12942581 | DOI:10.3390/jpm16020099

Premature Neuroimmune and Redox-Inflammatory Breakdown at the Prodromal Stage in Male and Female Triple-Transgenic Alzheimer's Disease Mice - February 26, 2026

Diseases. 2026 Feb 9;14(2):61. doi: 10.3390/diseases14020061.

ABSTRACT

BACKGROUND/OBJECTIVES: Homeostatic (nervous, immune and endocrine) systems and their communications network are crucial for health and aging rate. We previously reported behavioral and peritoneal leukocyte function alterations and oxidative-inflammatory stress in young female triple-transgenic (3xTg) mice for Alzheimer's disease (AD). Here, the deterioration of the homeostatic systems and their interplay was investigated, in an integrated way, at prodromal stages and in both sexes of 3xTg-AD mice.

METHODS: An integrative analysis of the behavioral profile, peripheral immune splenic and thymic leukocyte functions, splenic oxidative-inflammatory state, and plasmatic corticosterone in both sexes of 3xTg-AD mice at 4 months of age was compared to that of age- and sex-matched NTg counterparts.

RESULTS: The prodromal stage of 3xTg-AD, characterized by anxiety-like behaviors and disrupted exploration, was aligned with reduced chemotaxis, natural killer activity, and lymphoproliferation-especially in the spleen. In addition, 3xTg-AD mice exhibited lower anti-inflammatory (IL-10) and higher pro-inflammatory (IL-2, IL-1β, and TNF-α) cytokine concentrations and oxidative stress (higher oxidants and lower antioxidants). Several of these alterations displayed sex-dependent differences (worse in males). However, no differences in corticosterone were found.

CONCLUSIONS: These findings suggest that neuroimmune and redox-inflammatory dysfunctions, indicative of premature aging, emerge at the prodromal stage of AD, preceding corticosterone changes, unveiling a time lag in the neuroimmunoendocrine alterations in these animals. They may act as early indicators of premature aging in AD pathology and provide potential targets for sex-specific prodromal intervention.

PMID:41745099 | PMC:PMC12939257 | DOI:10.3390/diseases14020061

Spatial Patterns of Breast Cancer Risk Associated with Industrial and Environmental Pollutants: A Scoping Review - February 26, 2026

Toxics. 2026 Jan 30;14(2):139. doi: 10.3390/toxics14020139.

ABSTRACT

This scoping review examined published evidence linking environmental and industrial exposures to breast cancer, synthesizing studies conducted between 2015 and 2025. Using the Arksey and O'Malley framework, 51 peer-reviewed studies were identified and analyzed across five domains: study design, evidence quality, pollutant associations, geographic emphasis, and research gaps. Most studies used retrospective designs, primarily case-control, ecological, cross-sectional, and cohort approaches, which identified associations but could not establish causation. Evidence of quality varied due to heterogeneous environmental modeling methods, exposure to misclassification concerns, and unmeasured confounding, even though 86 percent of studies had sample sizes larger than 1000 cases. Pesticides, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were consistently associated with breast cancer, and nitrogen oxides (NOx), particulate matter (PM), and endocrine-disrupting chemicals (EDCs) also showed frequent significant associations. Research was geographically concentrated in North America and Europe, and few studies examined industrial hotspots or low-income regions. Gaps included the need for stronger epidemiological designs, multipollutant models, standardized exposure metrics, and clearer integration of significant environmental findings into public health protections. Overall, while evidence of pollution-related breast cancer risk continued to accumulate, the precautionary principle remained largely unimplemented. Advancing environmental policy, improving exposure transparency, and incorporating hotspot-based approaches are critical for reducing pollutant burdens and strengthening cancer prevention.

PMID:41745813 | PMC:PMC12944497 | DOI:10.3390/toxics14020139

PM<sub>2.5</sub>-Bound Organophosphate Esters and Childhood Sleep Disorders: Evidence from the Pearl River Delta Study - February 26, 2026

Toxics. 2026 Jan 29;14(2):134. doi: 10.3390/toxics14020134.

ABSTRACT

Although particulate matter has been associated with sleep problems, the effects of PM_2.5-bound organophosphate esters (OPEs) on children's sleep remain unclear. OPEs have neurotoxic and endocrine-disrupting effects that may disrupt sleep-wake regulation during neurodevelopment, supporting biological plausibility for sleep impacts. In this study, we quantified the individual and mixture effects of PM_2.5-bound OPEs on the sleep disorder domain. This cross-sectional study included 110,169 children aged 6-18 years from primary and secondary schools in the Pearl River Delta (PRD), China. Sleep disorders were evaluated using the validated Sleep Disturbance Scale for Children (SDSC). Elastic net and mixed effect models identified specific OPE-sleep associations, while weighted quantile sum regression evaluated mixture effects. All odds ratios indicate a change in the likelihood of sleep disorders per interquartile range (IQR) increase in OPE concentrations. The strongest individual associations were observed for TDCIPP with short sleep duration (OR = 1.56-1.61; moderate association), TEHP with short sleep duration (OR = 1.59-1.64; moderate association), and TPHP with overall sleep disorder (OR = 1.32-1.42; modest association). Combined OPE exposure was positively associated with all sleep disorder domains (ORs = 2.02-2.85; moderate-to-large associations). These results indicate that inhaling PM_2.5-bound OPE mixtures could negatively impact children's sleep health. This emphasizes a critical developmental period and highlights the importance of public health concerns related to emerging airborne contaminants.

PMID:41745808 | PMC:PMC12944893 | DOI:10.3390/toxics14020134

Dynamics of Endocrine Disruptor Exposure in Early Life: A Mother-Infant Hair Biomonitoring Study - February 26, 2026

Toxics. 2026 Feb 16;14(2):175. doi: 10.3390/toxics14020175.

ABSTRACT

BACKGROUND: Fetal and postnatal development appears to be influenced in multiple ways by exposure to endocrine-disrupting chemicals (EDCs). We used hair biomonitoring to assess the burden of selected EDCs-bisphenol S (BPS), parabens (PBs), triclosan (TCS), and organochlorine pollutants-in pregnant women and their children at birth and at ten months of follow-up.

METHODS: Hair samples were collected from pregnant women in Crete at delivery and from their infants shortly after birth and during follow-up. The assessment of EDCs' burden was performed using liquid and gas chromatography-mass spectrometry (LC-MS, GC-MS).

RESULTS: Pregnant mothers had higher BPS levels than their infants at birth, whereas at 10 months' follow-up, infants exhibited markedly higher BPS concentrations than both their birth levels and the maternal levels, indicating increasing postnatal exposure. Infants at birth had higher TCS levels than their mothers; these levels then declined at follow-up. In contrast, mothers contained higher levels of MeP, EthP, BenP, and ButP levels than those of infants, either at birth or at ten months' follow-up. Organochlorine compounds were present at low but measurable levels. Significant pairwise comparisons were observed for some of the EDC analytes, mostly between mothers and their infants and between mothers and infants at follow-up.

CONCLUSIONS: These findings demonstrate constant, compound-specific, and time-dependent EDC burdens, highlighting the importance of prenatal EDC exposure in infants at birth and at ten months' follow-up compared to that of mothers.

PMID:41745849 | PMC:PMC12945111 | DOI:10.3390/toxics14020175

Phthalate Metabolites in Maternal Urine and Breast Milk After Very Preterm Birth: Matrix Concordance - February 26, 2026

Toxics. 2026 Jan 30;14(2):141. doi: 10.3390/toxics14020141.

ABSTRACT

BACKGROUND: Exposure to environmental pollutants, especially endocrine-disrupting chemicals, disproportionately affects vulnerable populations like pregnant women, lactating mothers, and preterm infants. This study aimed to assess the detection patterns of DiNP-, DEP-, and DEHP-related metabolites in maternal urine and breast milk, examine agreement between matrices, and explore maternal factors associated with phthalate exposure.

METHODS: Fifty-five mothers who delivered at ≤32 gestational weeks and whose infants were hospitalized in the Neonatal Intensive Care Unit (NICU) were enrolled. Breast milk and urine samples were analyzed using a validated isotope-dilution LC-MS/MS method. Urinary phthalate metabolite concentrations were adjusted for specific gravity. Linear mixed-effects models with a random intercept for mother were used to examine associations between urinary and breast milk phthalate metabolite concentrations, assess temporal changes, and evaluate the influence of breast milk lipid content.

RESULTS: DEHP and DiNP metabolites were detected in nearly all maternal urine samples. Breast milk contained predominantly primary metabolites (MEHP and MiNP), while secondary oxidative metabolites were rarely detected. Urine concentrations consistently exceeded breast milk concentrations. Urinary and breast milk phthalate concentrations were not correlated across sampling periods, indicating limited matrix concordance.

CONCLUSIONS: Mothers of very preterm infants experience sustained phthalate exposure in the postpartum period; however, limited metabolite transfer to breast milk indicates that maternal urine remains the preferred biomonitoring matrix for assessing systemic phthalate exposure. Breast milk phthalate profiles exhibit compound-specific temporal changes and appear largely independent of concurrent urinary exposure biomarkers.

PMID:41745816 | PMC:PMC12944914 | DOI:10.3390/toxics14020141

Exposure to Phthalates and Alterations in Reproductive Hormones in Pregnant Women - February 26, 2026

Ecohealth. 2026 Feb 26. doi: 10.1007/s10393-026-01778-6. Online ahead of print.

ABSTRACT

Phthalates are ubiquitous environmental contaminants known for their endocrine-disrupting properties. Pregnancy is a particularly vulnerable period during which exposure to these compounds may adversely affect maternal health and fetal development. This study aimed to evaluate the exposure of pregnant women to phthalates, specifically diethyl phthalate (DEP), di-(2-ethylhexyl) phthalate (DEHP), and di-n-butyl phthalate (DnBP), and to investigate potential associations between urinary concentrations of their metabolites (MEP (monoethyl phthalate), MEHP (mono-(2-ethylhexyl) phthalate), and MnBP (mono-n-butyl phthalate)) and circulating reproductive hormone levels. A cross-sectional study was conducted on 384 pregnant women. Reproductive hormones (LH, FSH, testosterone, progesterone, estradiol, and prolactin) were quantified by electrochemiluminescence. Urinary concentrations of phthalate metabolites were measured using LC-MS/MS and normalized to creatinine levels. Phthalate metabolites were detected in the majority of samples (MEP: 97.4%; MEHP: 95.6%; MnBP: 92.9%). Mean concentrations were 83.50 ± 89.13 µg/g creatinine for MEP, 37.92 ± 41.08 µg/g for MEHP, and 44.64 ± 48.17 µg/g for MnBP. Phthalate detection frequencies did not differ significantly across residential regions, except for urinary MEHP concentrations, which were higher among women residing in the Eastern region of Algiers (53.039 µg/g creatinine). No significant differences in detection frequencies between 2022, 2023, and 2024 were observed; however, the highest urinary MEHP concentrations were recorded in 2022 (47.922 µg/g creatinine). Significant inverse associations were observed between urinary MEP and MEHP concentrations and plasma progesterone and testosterone levels (β_{MEP-progesterone}: - 0.216; β_{MEHP-progesterone}: - 0.523; β_{MEP-testosterone}: - 0.001; β_{MEHP-testosterone}: - 0.001). Estradiol levels were also negatively associated with MEP (β = - 23.301) and MnBP (β = - 33.241). Maternal exposure to phthalates was associated with alterations in reproductive hormone levels during pregnancy. These findings underscore the need to further investigate the potential implications of such hormonal disruptions for both maternal and fetal health.

PMID:41748857 | DOI:10.1007/s10393-026-01778-6

Phthalate Esters in Aquatic Ecosystems: A Multiscale Threat from Molecular Disruption to Ecological Risks - February 26, 2026

Toxics. 2026 Feb 23;14(2):185. doi: 10.3390/toxics14020185.

ABSTRACT

Phthalate esters (PAEs), ubiquitous plastic additives, have emerged as persistent contaminants in aquatic ecosystems, yet their propagation from molecular initiating events to ecosystem-level collapse remains poorly integrated. This review synthesizes current knowledge on the source-to-sink dynamics of PAEs, revealing a critical paradox in their bioaccumulation patterns: unlike classical persistent organic pollutants, high molecular weight PAEs exhibit distinct trophic dilution rather than biomagnification along food webs, driven by metabolic biotransformation in higher trophic organisms. Despite this dilution, PAEs trigger a bottom-up toxicity cascade. Driven by molecular initiating events, PAEs induce a range of adverse effects at the individual level, including immunotoxicity, neurotoxicity, endocrine disruption, metabolic dysfunction, and trans-trophic oxidative stress. Crucially, prolonged exposure drives epigenetic reprogramming, which reduces reproductive output, thereby threatening long-term population recruitment. These individual and population deficits could escalate into higher ecological consequences, specifically by diminishing benthic biological control over phytoplankton, dampening energy transfer efficiency, and simplifying community structure, thereby posing a potential threat to primary productivity and aquatic ecosystem sustainability. Despite recent advances, critical knowledge gaps remain, particularly regarding their cascading impacts on ecosystem services, as well as synergistic interactions between PAEs and other contaminants. In order to validate laboratory results with actual ecological risk assessments, future research should incorporate multi-scale models and quantitative adverse outcome Pathways as well as their synergistic interactions between PAEs and other contaminants, and advanced in vitro systems such as organoids. Resolving these issues is essential to reducing the risks that PAEs pose to aquatic environments.

PMID:41745859 | PMC:PMC12944614 | DOI:10.3390/toxics14020185

Exploring the Impact of Polychlorinated Biphenyls (PCBs) on the Development of MASLD: A Comprehensive Review - February 26, 2026

Cells. 2026 Feb 18;15(4):364. doi: 10.3390/cells15040364.

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is becoming the most common liver disease, affecting between 30 and 40% of the global population. MASLD is a multifaceted disease spectrum that is closely associated with obesity, insulin resistance, type 2 diabetes mellitus and, more broadly, metabolic syndrome. All these conditions increase the risk of liver-related mortality, which explains the intense research efforts in recent years to better elucidate its pathogenesis. The crucial impact of environmental pollutants on the development of MASLD is now well recognized. Polychlorinated biphenyls (PCBs) are environmental contaminants that act as endocrine disruptors. Recently, they have been associated with the development of diabetes, obesity, MASLD, and cancer. The association between liver diseases, namely toxicant-associated steatotic liver disease and steatohepatitis (TASLD and TASH, respectively), and occupational exposure to PCBs and other industrial chemicals has been documented by several lines of evidence, whereas the potential role of low-level environmental pollution in liver disease and in MASLD remains incompletely understood. Previous studies on animal models have shown that PCB exposure is associated with steatosis/steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma (HCC), altered liver enzymes, and mortality in exposed populations. This review investigates the mechanisms underlying hepatic steatogenesis in preclinical and animal models and analyzes the existing literature on the possible role of PCBs, together with the other conventional risk factors, in the development of MASLD in humans.

PMID:41744807 | PMC:PMC12939530 | DOI:10.3390/cells15040364

Bisphenol A and its analogues in thyroid diseases: Evidence from dysfunction, autoimmunity, and cancer - February 25, 2026

iScience. 2026 Feb 4;29(3):114890. doi: 10.1016/j.isci.2026.114890. eCollection 2026 Mar 20.

ABSTRACT

Bisphenol A (BPA) and its analogues are widely used industrial chemicals in the production of polycarbonate plastics, epoxy resins, and related polymeric materials. Their extensive production and application have led to pervasive environmental contamination, enabling human exposure via ingestion, inhalation, and dermal absorption. As endocrine disruptors, BPA and its analogues (such as bisphenol S and bisphenol F) can influence thyroid homeostasis through interference with hormone synthesis, metabolism, and receptor signaling pathways. Recent studies suggest that exposure to bisphenols may contribute to thyroid dysfunction, autoimmune thyroid disease, and possibly thyroid carcinogenesis. Although some BPA alternatives appear to exert thyroid disrupting effects comparable to BPA, limited epidemiological evidence precludes a clear assessment of their relative safety. Given the ongoing rise in global bisphenol exposure, clarifying molecular mechanisms, defining susceptible subpopulations, and improving regulatory oversight are critical steps toward reducing thyroid-related health risks.

PMID:41736862 | PMC:PMC12927062 | DOI:10.1016/j.isci.2026.114890

Distinct Sorption and Rejection Behavior of Hydrophobic Endocrine-Disrupting Compounds by Chlorinated Polyamide Nanofiltration Membranes: Mechanisms and Implications - February 25, 2026

Environ Sci Technol. 2026 Feb 25. doi: 10.1021/acs.est.5c14877. Online ahead of print.

ABSTRACT

Effective removal of hydrophobic endocrine-disrupting compounds (EDCs) using polyamide nanofiltration (NF) membranes remains a challenge in membrane-based water treatment. A common belief is that the sorption of hydrophobic EDCs is key to their rejection, while high sorption often leads to low rejection. However, this study reported distinct sorption-rejection behavior of EDCs by various chlorinated polyamide membranes. Specifically, the chlorinated NF90 membrane exhibited significantly reduced sorption and, thus, enhanced rejection for EDCs. This is primarily attributed to the enhanced hydrophilic carboxyl groups through chlorination-induced hydrolysis, which can suppress the hydrophobic interactions between the membrane and the EDCs. More interestingly, the chlorinated VNF1 membrane demonstrated higher sorption but also higher rejection of EDCs than that of the virgin membrane. The high sorption can be attributed to the strong hydrophobic interaction between EDCs and the hydrophobic chlorine attached to the membrane. Meanwhile, the large size of chlorine also strengthened membrane size exclusion, thereby enhancing its rejection of EDCs. Such enhanced size exclusion overperformed the impact of increased sorption, thus leading to enhanced rejection. These findings elaborate the existing membrane sorption-rejection framework and offer valuable insights for the rational design of advanced NF membranes aiming for the effective elimination of EDCs in water and wastewater treatment.

PMID:41739532 | DOI:10.1021/acs.est.5c14877

The Critical Nature of a Robust Weight of Evidence Assessment to Conclude on Endocrine Disruption Using Diflufenican as a Case Study - February 25, 2026

Regul Toxicol Pharmacol. 2026 Feb 23:106068. doi: 10.1016/j.yrtph.2026.106068. Online ahead of print.

ABSTRACT

Diflufenican (DFF) is a herbicide registered globally since the mid-1980s and submitted for renewal in the European Union (EU) in 2016. The submission included extensive data from repeat-dose studies, reproductive and developmental toxicity studies and ToxCast/Tox21 high-throughput in vitro screening data to allow an assessment of endocrine adversity and activity. Despite no evidence of estrogen, androgen, thyroid, or steroidogenic (EATS) mediated patterns of adversity, regulatory reviewers deemed the investigations insufficient due to outdated guidelines lacking EATS parameters. Such a shortfall is common for many plant protection products (PPPs) undergoing renewal due to advances in scientific methodology. The EU's stepwise testing strategy addresses this by requiring OECD Level 2 and Level 3 studies to assess activity. If negative, further testing is unnecessary. However, DFF's positive result in the in vitro steroidogenesis assay (Level 2) triggered an OECD Level 5 extended one-generation reproductive toxicity (EOGRT) study. The EOGRT data confirmed previous findings that DFF does not cause endocrine disruption (ED) related adversity. A comprehensive weight of evidence (WoE) assessment of existing data could have sufficed to conclude DFF's lack of ED properties, preventing unnecessary animal testing. This underscores the need to enhance WoE methodologies to better utilize existing data in regulatory evaluations.

PMID:41740827 | DOI:10.1016/j.yrtph.2026.106068

Hydrophobicity-driven inhibition of human and rat 11β-hydroxysteroid dehydrogenase 2 by isothiazolinone biocides: Insights from enzyme kinetics and SPR interactions - February 25, 2026

Comp Biochem Physiol C Toxicol Pharmacol. 2026 Feb 23:110492. doi: 10.1016/j.cbpc.2026.110492. Online ahead of print.

ABSTRACT

Isothiazole (IT) derivatives are a class of broad-spectrum antimicrobial agents. Despite their widespread use, their effects on the glucocorticoid endocrine system remain unclear. This study investigates the potential interaction of IT biocides with 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), a key enzyme in glucocorticoid metabolism. The inhibitory strength and structure-activity relationship (SAR)/3D-QSAR of IT and its 6 derivatives on human (placental) and rat (renal) 11β-HSD2 were assessed. The results demonstrated that the IT biocides exhibited a range of inhibitory potencies against human 11β-HSD2, with half-maximal inhibitory concentration (IC₅₀) values spanning from 11.76 μM to greater than 100 μM. These IT biocides inhibited rat 11β-HSD2 in a similar order. Surface Plasmon Resonance analysis revealed that dichlorooctylisothiazolinone (KD = 12.1 μM) had higher affinity to human 11β-HSD2 than benzisothiazolinone (KD = 14.9 μM). Bivariate correlation analysis demonstrated a positive correlation between pIC₅₀ values and hydrophobicity, molecular weight, heavy atom number, volume, and Log D. Molecular docking analysis indicated that these IT biocides bind to cofactor binding sites or between the steroid and cofactor interface. Additionally, 3D-QSAR modeling highlighted the influence of hydrogen bond acceptors and hydrophobic regions on the inhibitory activity of these compounds. The suppression of cortisol metabolism in intact placental BeWo cells is influenced not only by their inhibitory potency on human 11β-HSD2 but also by their cell membrane permeability. These findings provide valuable insights into the endocrine-disrupting potential of IT biocides and their interactions with 11β-HSD2.

PMID:41740912 | DOI:10.1016/j.cbpc.2026.110492

Investigating ovarian effects of perfluorooctanoic acid in post-pubertal pigs during thermal neutral and heat stress conditions - February 25, 2026

J Anim Sci. 2026 Feb 25:skag062. doi: 10.1093/jas/skag062. Online ahead of print.

ABSTRACT

Perfluorooctanoic acid (PFOA) is associated with disrupted female endocrine and reproductive function. In this study, the ovarian impact of PFOA exposure was investigated in post-pubertal pigs housed in thermal neutral (TN) or heat stress (HS) environments. Gilts (n = 48) were housed in either TN conditions (21.0 ± 0.10 °C) or cyclical HS (32.2 ± 0.1 °C to 26.2 ± 0.1 °C) for 19 d and assigned randomly to TN vehicle control (TC; n = 12), TN PFOA (TP; n = 12, 70 ng PFOA/kg), HS control (HC; n = 12), and HS PFOA (HP; n = 11; 70 ng PFOA/kg) treatments. Relative to TC, ovarian weight was decreased in TP (P = 0.03) and tended to be decreased in HP (P = 0.08). Follicular fluid estradiol tended (P = 0.08) to be decreased in HP relative to HC gilts. Dominant follicle size, vulva size, uterine weight and follicular fluid progesterone level were not altered by treatment. The number of ovarian primordial, primary, and secondary follicles was not affected by PFOA treatment, but tertiary follicles tended (P = 0.08) to be decreased by HS. In HP gilts, there were more primordial (P = 0.05), secondary (P = 0.002) and empty (P = 0.008) follicles and a tendency for increased primary (P = 0.06) and tertiary (P = 0.08) follicles compared to TC gilts. The abundance of ovarian microsomal epoxide hydrolase (EPHX1) was reduced in HP relative to TC (P = 0.005) and HC (P = 0.006) gilts. In TP gilts, 3β-hydroxysteroid dehydrogenase (3BHSD) was reduced (P = 0.02) and both cytochrome P450 family 19 subfamily A member 1 (CYP19A1) tended (P = 0.06) to be reduced, while 3BHSD tended to be reduced in HP compared to HC gilts (P = 0.09). Thus, there were ovarian impacts of PFOA exposure in TP gilts with some additive impacts in heat-stressed pigs.

PMID:41741380 | DOI:10.1093/jas/skag062

Mechanistic insights into triclosan-induced hepatotoxicity: A network toxicology and molecular docking approach - February 25, 2026

PLoS One. 2026 Feb 25;21(2):e0333244. doi: 10.1371/journal.pone.0333244. eCollection 2026.

ABSTRACT

BACKGROUND: Triclosan (TCS) is an artificially synthesized broad-spectrum antimicrobial agent, which is widely used in personal care products. It is a new endocrine disruptor and has potential health hazards to human body.

OBJECTIVE: Based on network toxicology and molecular docking technology, the compounds that may cause hepatotoxicity in triclosan were predicted and the mechanism was discussed.

METHOD: From April to May 2025, the targets of triclosan were identified using databases such as STITCH, CTD, Swiss Target Prediction, and TargetNet. Additionally, gene targets associated with liver toxicity were identified from the GeneCards and OMIM databases. The intersection of triclosan-targets and liver toxicity-related gene targets was used to identify candidate targets. Using the String platform, a protein interaction network was constructed for these candidate targets to identify core functional modules within the network. The candidate targets were analyzed for GO and KEGG enrichment using DAVID, and a triclosan-liver toxicity-target pathway network was constructed using Cytoscape 3.10.1 software. Network topology analysis was conducted to screen for key components and targets. Finally, molecular docking was performed on the core targets using CB-Dock2.

RESULTS: 683 candidate targets for liver toxicity caused by triclosan were identified. The core targets for liver toxicity from triclosan production include TP53, EGFR, AKT1, IL6, JUN, and FN1. Molecular docking analysis shows that the binding free energy of triclosan with these core targets is less than -5.5 kcal/mol. The comprehensive analysis results showed that the liver damage caused by triclosan was mainly related to the activation of Pathways in cancer, Endocrine resistance, AGE-RAGE signaling pathway in diabetic complications, hepatitis B, and lipid and atherosclerosis signaling pathways.

CONCLUSION: The potential targets and molecular mechanisms of triclosan (TCS) induced liver injury were investigated, and 6 key targets and 5 pathways were identified, providing a new paradigm for evaluating the health risks caused by environmental pollutants.

PMID:41739763 | PMC:PMC12935200 | DOI:10.1371/journal.pone.0333244

Associations of prenatal exposure to bisphenols and phthalates with the fetoplacental ratio in the New York University Children's Health and Environment Study (NYU CHES) - February 25, 2026

Ecotoxicol Environ Saf. 2026 Feb 24;312:119925. doi: 10.1016/j.ecoenv.2026.119925. Online ahead of print.

ABSTRACT

Fetoplacental ratio (FPR), the ratio of birthweight (BW) to placental weight (PW), indicates placental efficiency. Changes in FPR are linked to poor pregnancy outcomes and child health risks. Bisphenols and phthalates are endocrine disruptors found in plastics and personal care products that can cross the placenta and have been linked to pregnancy complications and adverse child health outcomes. We examined prenatal exposure to these chemicals in relation to FPR as a possible explanation for these risks. Our analysis included 393 participants in the New York University Children's Health and Environment Study with data on prenatal chemical exposure, BW, and PW from singleton live births. We calculated molar sums of bisphenols and of metabolites of low and high molecular weight (LMW, HMW) phthalates, diethylhexyl phthalate (DEHP), and antiandrogenic phthalates. Linear regression models were adjusted for maternal age, prepregnancy BMI, parity, gestational age at delivery, and fetal sex. Analyses were stratified by fetal sex. HMW were positively associated with FPR in the combined fetal sex sample (beta=0.26, [0.01, 0.50]) with a similar trend for DEHP and antiandrogenic phthalates (betas=0.21 [-0.04, 0.45] and 0.21 [-0.04, 0.45], respectively). Stratified analyses revealed that these results were driven by females, among whom LMW were also associated with higher FPR (beta=0.23 [0.003, 0.45]). No associations were observed between chemicals and BW in either combined or sex-stratified models. In contrast, HMW, LMW, DEHP, di-n-octylphthalate and bisphenols had negative associations with PW, suggesting placental growth as a target for phthalate-mediated endocrine disruption.

PMID:41740550 | DOI:10.1016/j.ecoenv.2026.119925

Obesogens in Prostate Cancer: An Endocrine and Metabolic Threat - February 25, 2026

Curr Obes Rep. 2026 Feb 25;15(1):14. doi: 10.1007/s13679-026-00690-y.

ABSTRACT

PURPOSE OF REVIEW: This review addresses the contribution of obesogenic endocrine-disrupting chemicals (EDCs) to prostate carcinogenesis. It provides an in-depth overview of obesogens, tracing their mechanisms of action and effects impacting prostate cell fate. The direct effects of obesogens in disrupting adipose tissue and metabolic homeostasis, as well as disturbing prostate cells, are discussed, along with the potential indirect effects mediated by the dysregulation of the adipose tissue.

RECENT FINDINGS: Obesogens represent a group of EDCs that interfere with endocrine and metabolic processes, underpinning the spread of obesity. Moreover, the ubiquitous presence in the environment, the ability to accumulate in adipose tissue and the broad range of effects targeting several biological pathways highlight that obesogens can be detrimental to human health beyond their action on promoting obesity. Prostate cancer (PCa) is a hormone-dependent cancer for which environmental influences and obesity are established risk factors, with emerging evidence suggesting that obesogens may affect its development and progression.

SUMMARY: The available data indicate that obesogens may contribute to the development of PCa. They can have direct actions in prostate cells modulating signalling pathways that drive tumour aggressiveness. Moreover, the adipose tissue dysregulated by obesogens can acquire an obesity-like phenotype, which may play a crucial role in facilitating tumour growth. Further research is needed to clarify the liaison between obesogen-induced dysregulation of the periprostatic adipose tissue depot and PCa aggressiveness. Unravelling this complex crosstalk will be pivotal for identifying novel therapeutic strategies and preventing aggressive PCa, especially in obese patients.

PMID:41739363 | PMC:PMC12935831 | DOI:10.1007/s13679-026-00690-y

Exposure to per- and polyfluoroalkyl substance (PFAS) mixtures increases papillary thyroid cancer risk and clinicopathological aggressiveness: Findings from a case-control study and risk assessment - February 25, 2026

Ecotoxicol Environ Saf. 2026 Feb 24;312:119941. doi: 10.1016/j.ecoenv.2026.119941. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) have been reported to possess endocrine-disrupting and tumor-promoting activity. However, the association between PFAS exposure and papillary thyroid carcinoma (PTC) remains poorly understood. This case-control study investigated whether PFAS exposure is associated with PTC risk, and if so, whether this association is mediated through thyroid hormone disruption and linked to specific clinicopathological and genetic features of the tumor. We recruited 60 PTC patients and 60 healthy controls from Shanghai, China. Serum levels of PFAS and thyroid hormones were measured. Multiple linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were used to analyze associations between PFAS mixtures and individual congeners with PTC risk and thyroid function. A chronic reference dose (CRfD) for PFOS was derived from animal studies using benchmark dose modeling. PTC patients had significantly elevated serum levels of several PFAS, including perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), and 8:2 chlorinated perfluoroalkyl ether sulfonic acid (8:2Cl-PFESA), compared to controls. WQS regression indicated a significant positive association between PFAS mixture exposure and PTC risk (OR = 2.01, p = 0.023), with 8:2CI-PFESA, PFDoDA, PFBS, and PFOS identified as the primary contributors. Furthermore, specific PFAS congeners were associated with more aggressive tumor features, including advanced TNM stage and with high-risk genetic alterations such as TERT mutation, and RAS&TERT promoter co-mutations. In terms of hormonal effects, Furthermore, perfluorobutanesulfonic acid (PFBS) and 8:2Cl-PFESA showed significant negative dose-response relationships with FT3 levels in patients, suggesting a potential link between PFAS-induced thyroid disruption and carcinogenesis. The derived oral CRfD for PFOS, based on triiodothyronine reduction, was 40 ng/kg·bw/day. Our findings indicate that PFAS exposure is associated with an increased risk of PTC, potentially through mechanisms involving thyroid hormone disruption and the promotion of more aggressive tumor characteristics. These results underscore the need for stricter regulation of industrial PFAS emissions and enhanced thyroid function monitoring in high-risk populations.

PMID:41740556 | DOI:10.1016/j.ecoenv.2026.119941

Ecotoxicol Environ Saf. 2026 Feb 24;312:119941. doi: 10.1016/j.ecoenv.2026.119941. Online ahead of print.

ABSTRACT

PMID:41740556 | DOI:10.1016/j.ecoenv.2026.119941

PM(2.5)-induced ferroptosis via the miR-188-3p/GPX4 axis disrupts renal erythropoietin production - February 24, 2026

Toxicol Appl Pharmacol. 2026 Feb 22;510:117774. doi: 10.1016/j.taap.2026.117774. Online ahead of print.

ABSTRACT

Exposure to fine particulate matter (PM_2.5) is a significant environmental risk factor for renal pathologies, including chronic kidney disease and acute kidney injury. Ferroptosis is increasingly implicated in kidney pathology or PM_2.5-induced toxicology. However, the direct mechanistic link between PM_2.5 and renal ferroptosis, particularly within an endocrine context, remains elusive. In this study, pathological injury, kidney fibrosis, lipid peroxidation (LPO), iron ions, and ferroptosis effects were measured in in vivo and in vitro experiments following PM_2.5 exposure. Ferroptosis was visualized by confocal microscopy of glutathione (GSH)/reactive oxygen species (ROS). Next, the glutathione peroxidase-4 (GPX-4) function and its regulation by miR-188-3p were verified. EPO and aldosterone levels were also measured. Results showed that PM_2.5 exposure induced renal pathological injury and fibrosis, along with the abnormal changes in the levels of related factors (IL-6, TNF-α, Fibronection, Col4A2, TGF-β, and KIM-1). At the same time, PM_2.5 caused ferroptosis, as evidenced by iron overload, elevated ROS and LPO, reduced GSH levels, and dysregulation of ferroptosis-related proteins (GPX-4 and Acsl4). The critical role of GPX-4 was confirmed by the ferroptosis inhibitor ferrostatin-1, which attenuated these injurious effects. The miR-188-3p mimic and inhibitor experiments validated miR-188-3p regulation of GPX-4. Of note, PM_2.5 significantly reduced EPO levels compared with controls and was linked to ferroptosis. Our findings elucidate a novel miR-188-3p/GPX-4/ferroptosis pathway of PM_2.5-induced kidney injury, accompanied by renal EPO endocrine disruption. These also reveal potential therapeutic targets for combating air pollution-related kidney diseases.

PMID:41734873 | DOI:10.1016/j.taap.2026.117774

Decoding tamoxifen on idiopathic pulmonary fibrosis: integrating network toxicology and multi-omics - February 24, 2026

Int J Surg. 2026 Feb 1;112(2):2696-2716. doi: 10.1097/JS9.0000000000003620. Epub 2025 Oct 10.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Tamoxifen, a breast cancer therapeutic agent, raises environmental concerns due to its persistence and bioaccumulation potential, but its role as an endocrine disruptor in IPF pathogenesis remains unclear.

MATERIALS AND METHODS: We integrated computational toxicity prediction (ProTox-3.0/ADMETlab-3.0), FDA Adverse Event Reporting System (FAERS) pharmacovigilance, and Mendelian randomization (MR) to establish causal tamoxifen-IPF links. Network toxicology identified shared targets, with protein-protein interactions network construction revealing seven hubgenes. Multi-omics validation included: transcriptomics (GSE110147/GSE53845) for hubgenes expression, immune infiltration and single-cell RNA (scRNA) sequencing (GSE159354) for cellular associations, and machine learning (least absolute shrinkage and selection operator/support vector machine-recursive feature elimination/random forest) for biomarker identification. Mechanistic studies involved miRNA expression data (GSE27430) to explore the upstream regulators of key genes, and molecular docking to validate drug targets. Finally, in vivo validation was performed in C57BL/6 mice administered intraperitoneal tamoxifen, with assessment of pulmonary inflammation and fibrosis using bronchoalveolar lavage fluid protein exudation, cell counts, lung wet/dry weight ratio, and Ashcroft score, along with evaluation of epidermal growth factor receptor (EGFR)/phosphorylated EGFR (p-EGFR) and miRNA-432-3p expression.

RESULTS: Computational toxicity prediction revealed tamoxifen's high respiratory toxicity potential, corroborated by FAERS-reported lung fibrosis associations, and MR confirmed causal IPF risk. Network toxicology identified seven hubgenes functionally enriched in miRNA regulation, with multi-omics validation revealing a critical EGFR dysregulation pattern where transcriptional downregulation contrasted with post-translational hyperactivation evidenced by elevated p-EGFR in fibrotic lungs. Mechanistically, miR-432-3p was upregulated in IPF and confirmed to directly target EGFR, while molecular docking demonstrated tamoxifen's preferential binding to miR-432-3p over EGFR. This tamoxifen-miRNA-EGFR axis drove pulmonary fibrosis with concurrent p-EGFR and mmu-miR-432 elevation in vivo.

CONCLUSION: Tamoxifen promotes IPF via miR-432-3p-mediated EGFR suppression, establishing it as a pulmonary toxicant. Integrated network toxicology identifies EGFR as a diagnostic biomarker, highlighting environmental and clinical risks of tamoxifen exposure.

PMID:41731859 | DOI:10.1097/JS9.0000000000003620

LINE-1 Activation in Endocrine-Related Cancers: Molecular Mechanisms and Translational Implications - February 24, 2026

Mol Cancer Res. 2026 Feb 24. doi: 10.1158/1541-7786.MCR-25-0682. Online ahead of print.

ABSTRACT

LINE-1 retrotransposons are increasingly recognized as active molecular players in tumorigenesis, particularly through mechanisms involving genomic instability, epigenetic deregulation, and disruption of transcriptional networks. However, their specific role in endocrine-related cancers remains underexplored despite accumulating evidence of widespread LINE-1 derepression in tumors of the thyroid, adrenal, pituitary, and prostate glands. In this Review, we provide a focused synthesis of the mechanistic consequences of LINE-1 reactivation in endocrine tumors. We discuss how hypomethylation of LINE-1 loci and overexpression of retrotransposon-encoded proteins (ORF1p and ORF2p) may contribute to DNA damage, copy number alterations, and impaired p53 signaling. We also explore emerging evidence that ORF1p may act as a co-regulator of nuclear hormone receptors, thereby linking retroelement biology with hormone-dependent tumor behavior. Beyond these molecular insights, we highlight translational opportunities rooted in LINE-1 biology, including the use of ORF1p as a surrogate biomarker of epigenetic instability, and therapeutic strategies targeting the retrotransposon life cycle. By bridging foundational mechanisms with endocrine-specific tumor phenotypes, this Review positions LINE-1 derepression as a unifying framework with both biological and clinical relevance in endocrine-related cancers.

PMID:41733430 | DOI:10.1158/1541-7786.MCR-25-0682

Polydiacetylene (PDA) coated paper-based fluorescence sensor for the detection and quantification of bisphenol - February 24, 2026

Lab Chip. 2026 Feb 24. doi: 10.1039/d5lc00821b. Online ahead of print.

ABSTRACT

Bisphenol (BPA) is a common environmental contaminant found in water, food, packaging, and human biological samples, raising significant health concerns due to its endocrine-disrupting properties, particularly its interference with estrogen receptors. We have developed a novel, portable paper-based sensor that utilizes a polydiacetylene (PDA) dye coated on filter paper. This sensor exhibits a distinct, concentration-dependent color change from blue to red when exposed to BPA. The colorimetric and fluorescence responses are driven by hydrogen bonding interactions between BPA's phenolic hydroxyl (OH) groups and the carbonyl groups of PDA's carboxylic acid. The sensor's performance was characterized using techniques such as FT-IR, Raman spectroscopy, scanning electron microscopy, and fluorescence microscopy. Our method allows for rapid, cost-effective, and sensitive detection and quantification of BPA by correlating digital image RGB values or fluorescence intensity with BPA concentration. We achieved a highly linear calibration with an R² value of 0.99, enabling dual-mode detection. This sensor offers a promising tool for on-site BPA monitoring in both environmental and medical contexts, overcoming the limitations of traditional assays and enhancing public health protection against this hazardous chemical.

PMID:41733063 | DOI:10.1039/d5lc00821b

Role of constitutive androstane receptor in developmental toxicology: linking chemical exposure, nutrition, and disease susceptibility - February 24, 2026

Crit Rev Toxicol. 2026 Feb 24:1-17. doi: 10.1080/10408444.2026.2623026. Online ahead of print.

ABSTRACT

The constitutive androstane receptor (CAR) is a xenobiotic-sensing nuclear receptor that regulates gene transcription involved in drug metabolism, especially in the liver. CAR activation influences detoxification pathways and disrupts endocrine homeostasis, notably thyroid hormone (TH) signaling. THs are crucial for neurodevelopment, skeletal maturation, and metabolic regulation. When activated by antiseizure medications, such as phenobarbital, or environmental chemicals, such as perfluoroalkyl substances, CAR induces hepatic enzymes, including UDP-glucuronosyltransferases (UGTs), which increase the clearance of THs and raise thyroid-stimulating hormone levels. Developmental exposure to CAR activators in rodents has been linked to reduced circulating and brain TH levels, resulting in impaired neurodevelopmental outcomes. Given that CAR expression is very low in fetal and neonatal livers, maternal CAR activation may significantly disrupt fetal TH signaling. Additionally, CAR modulates host gene expression affecting microbial composition and bile acid homeostasis, with emerging evidence connecting it to early-life metabolic programming, including low birth weight. Epigenetic changes caused by CAR agonists during the neonatal period can persist into adulthood at least in rodents, suggesting a potential role of CAR in the developmental origins of health and disease, or DOHaD. While it is essential to consider species differences in ligand specificity and UGT isoform expression when extrapolating findings from rodents into humans, CAR is increasingly recognized as a mediator between environmental exposure and endocrine-metabolic disruption. This review integrates animal and human evidence to highlight the critical yet underappreciated functions of CAR in mediating developmental toxicity and long-term health outcomes.

PMID:41733502 | DOI:10.1080/10408444.2026.2623026

Role of constitutive androstane receptor in developmental toxicology: linking chemical exposure, nutrition, and disease susceptibility - February 24, 2026

Crit Rev Toxicol. 2026 Feb 24:1-17. doi: 10.1080/10408444.2026.2623026. Online ahead of print.

ABSTRACT

PMID:41733502 | DOI:10.1080/10408444.2026.2623026

Retraction notice to 'Physico-chemical and biological remediation techniques for the elimination of endocrine-disrupting hazardous chemicals' [Environ. Res. 232 (2023) 116363] - February 24, 2026

Environ Res. 2026 Feb 23;296:124050. doi: 10.1016/j.envres.2026.124050. Online ahead of print.

NO ABSTRACT

PMID:41734504 | DOI:10.1016/j.envres.2026.124050

Nutrient and endocrine factors affecting impaired growth in pediatric mitochondrial diseases - February 24, 2026

Endocrinol Diabetes Metab Case Rep. 2026 Feb 18;2026(1):EDM250140. doi: 10.1530/EDM-25-0140. Print 2026 Jan 1.

ABSTRACT

SUMMARY: Mitochondrial diseases cause systemic failure of energy production and can manifest as various disorders of hormone production and secretion from endocrine organs. These effects can prevent normal growth in children, resulting in adults of short stature. We therefore explored the nutritional and endocrinological status of pediatric mitochondrial disease patients with impaired growth. Four Japanese patients with genetically diagnosed mitochondrial disease were studied (one male and three females, aged 4-22 years). The age of onset ranged from 0 months to 7 years, and the causal genes identified were mtDNA, PDHA1, and NARS2 (in two sibling patients). Two patients were diagnosed with small for gestational age at birth, and their current height standard deviation scores ranged from -1.9 SD to -6.4 SD. Mitochondrial diseases can present as impaired growth with dysfunction of various organs, depending on the causal gene and the degree of heteroplasmy. Our patients had demonstrated low T3 syndrome and reduced IGF1 levels, which appeared to be influenced by impaired nutritional status. These findings emphasize the need for careful monitoring of growth trajectories alongside nutritional and endocrine evaluations to improve clinical management.

LEARNING POINTS: Mitochondrial diseases can disrupt endocrine function involving the GH-IGF1 axis and the thyroid and gonadal systems, leading to impaired growth during childhood. Patients with early-onset mitochondrial disease tend to experience severe symptoms and pronounced growth impairment. Children with mitochondrial diseases often show low IGF1 levels, low T3 syndrome, and delayed bone age, reflecting endocrine dysfunction commonly observed in chronic systemic diseases and the further influence of suboptimal nutritional status.

PMID:41734464 | PMC:PMC12921390 | DOI:10.1530/EDM-25-0140

Integrative computational and experimental analysis identifies MEK-mediated carcinogenic effects of bisphenol A and diethyl phthalate in head and neck cancer - February 24, 2026

Ecotoxicol Environ Saf. 2026 Feb 23;312:119924. doi: 10.1016/j.ecoenv.2026.119924. Online ahead of print.

ABSTRACT

We investigated the carcinogenic effects of four endocrine-disrupting chemicals-bisphenol A (BPA), diethyl phthalate (DEP), dimethyl phthalate (DMP), and dioctyl phthalate (DOP)-in nasopharyngeal carcinoma (NPC) and thyroid carcinoma (THCA) using an integrated toxicogenomic-machine learning-docking-experimental pipeline. Intersection analysis identified 31 NPC-related overlapping genes and 39 THCA-related overlapping genes, with 19 shared core targets across both malignancies. These shared targets were enriched in oncogenic signaling pathways including Mitogen-activated protein kinase （MAPK）, Phosphoinositide 3-Kinase-Protein Kinase B (PI3K-AKT), and Janus kinase/signal transducers and activators of transcription (JAK/STAT). A multi-algorithm machine learning framework constructed 113 predictive models and prioritized six diagnostic genes (CCNA2, CDK2, MET, F2, TYMS, PPARG). High expression of CCNA2 (HR=1.43, p = 0.016), CDK2 (HR=1.66, p = 0.002), MET (HR=1.58, p = 0.002), and PPARG (HR=1.45, p = 0.0072) was associated with worse overall survival, whereas TYMS and F2 were not significant. Molecular docking showed stable ligand-protein binding with energies from -5.2 to -8.1 kcal·mol⁻¹ , with the strongest affinities observed for BPA-CDK2 (-8.1) and BPA-PPARG (-8.1); DEP also showed strong binding to CDK2 (-7.0). In vitro, BPA and DEP (but not DMP/DOP) increased colony formation (p < 0.01), accelerated wound closure, upregulated oncogenic genes (e.g., CDK2/MET/CCNA2; p < 0.05), and elevated p-MEK without changing total MEK in 5-8 F and TPC-1 cells. Collectively, BPA and DEP promote head and neck tumor progression through MEK pathway activation and cell-cycle dysregulation.

PMID:41734620 | DOI:10.1016/j.ecoenv.2026.119924

Structural and mechanistic insights into industrial phenolic compounds as potent inhibitors of human and rat 5α-reductase 1 - February 24, 2026

Ecotoxicol Environ Saf. 2026 Feb 23;312:119914. doi: 10.1016/j.ecoenv.2026.119914. Online ahead of print.

ABSTRACT

This study identifies environmental chemicals 4-nonylphenol, 4-dodecylphenol, pentabromophenol, and popular anesthetics drug propofol as moderate to potent inhibitors of human and rat 5α-reductase type 1 (5α-R1), revealing novel endocrine-disrupting mechanisms in human brain cell and rat brain microsomes. Pentabromophenol exhibited the highest potency (IC₅₀ = 1.71 µM for human 5α-R1) with mixed/noncompetitive inhibition, supported by Surface Plasmon Resonance binding (KD = 1.22 µM). A 3D-QSAR pharmacophore model (Hypo1) highlighted critical structural features, including a hydrogen-bond acceptor and hydrophobic interactions, explaining pentabromophenol efficacy. Species differences emerged, with human 5α-R1 showing high pentabromophenol binding affinity (-6.80 kcal/mol via halogen bonds with Arg176). Inhibition may reduce neurosteroids (e.g., allopregnanolone) and androgens (e.g., dihydrotestosterone). These findings underscore industrial phenolic compound capacity to dysregulate neurosteroid homeostasis in a structure- and species-dependent manner, highlighting their endocrine-disrupting risks.

PMID:41734625 | DOI:10.1016/j.ecoenv.2026.119914

Role of lactic acid-mediated ALKBH5 in depression induced by blue light exposure at night - February 24, 2026

Ecotoxicol Environ Saf. 2026 Feb 23;312:119928. doi: 10.1016/j.ecoenv.2026.119928. Online ahead of print.

ABSTRACT

Artificial light at night (ALAN) has been classified as a significant environmental endocrine disruptor. Excessive exposure to ALAN has associated with an increased risk of depression. With the extensive use of high-density blue light LED screens, the risk of blue light exposure at night has increased. Animal studies have suggested a close relationship between blue light and depression, but the research on human population is limited. The mechanisms linking blue light to depression require in-depth investigation. We investigated whether nighttime artificial blue light exposure (NABLE) serves as a potential independent risk factor for depression and explored its underlying molecular mechanisms. A case-control study demonstrated that prolonged nighttime device use (> 4 h), high blue-light display patterns, and the use of nightlights during sleep were significantly associated with depressive symptoms in adolescents. This association was independent of demographic and sleep-related factors. Machine learning analyses confirmed these exposures as key predictors of depression. Our previous experimental work demonstrated that blue light exposure during sleep (BLS) induced depression-like behaviors in rodents. Building upon this, we have now reported that BLS elevates lactic acid levels in the lateral habenula (LHb), which upregulates the RNA demethylase ALKBH5 and modifies N⁶-methyladenosine (m⁶A) level. This cascade disrupts neuronal plasticity and induces depression-like phenotypes. Further validating the mechanism, LHb-specific ALKBH5 knockdown reduced both behavioral and synaptic abnormalities, while peripheral blood samples from adolescents with high NABLE exposure exhibited increased Alkbh5 expression. In conclusion, our findings indicate that NABLE is significantly associated with adolescent depression. The identified lactic acid-ALKBH5-m⁶A axis correlates environmental light exposure with neuroplasticity and mood regulation. These findings provide mechanistic insight into environmentally light-associated depression and highlight the significance of managing nocturnal blue light exposure as a potential preventive strategy for adolescent mental health.

PMID:41734626 | DOI:10.1016/j.ecoenv.2026.119928

The role of sleep stages in the regulation of erectile function: impacts of REM sleep fragmentation - February 24, 2026

Int J Impot Res. 2026 Feb 24. doi: 10.1038/s41443-026-01240-9. Online ahead of print.

ABSTRACT

Erectile function is a complex neurovascular process influenced by multiple physiological systems, including autonomic regulation, vascular integrity, and endocrine balance. Sleep-related erections (SRE), which occurs predominantly during rapid eye movement sleep (REM), plays a critical role in maintaining erectile physiology by ensuring periodic oxygenation of penile tissue and preventing fibrosis. Sleep fragmentation, particularly disruption of REM sleep, has been increasingly recognized as a contributing factor to erectile dysfunction (ED), with mechanisms involving heightened sympathetic activity, impaired parasympathetic vasodilation, and neuroendocrine dysregulation. Sleep disorders, such as obstructive sleep apnea and chronic sleep deprivation are associated with reduced SRE frequency, increased oxidative stress, and decreased nitric oxide bioavailability, all of which contribute to endothelial dysfunction and erectile impairment. Ageing exacerbates these issues by further reducing SRE occurrence and increasing the prevalence of sleep disturbances. Therapeutic strategies aimed at optimizing sleep architecture and its quality, including pharmacological, hormonal, and neuromodulatory interventions, may provide promising avenues for mitigating ED and promoting healthy ageing. This review highlights the interplay between sleep physiology, erectile function, and therapeutic implications, underscoring the importance of sleep optimization in ED management.

PMID:41735516 | DOI:10.1038/s41443-026-01240-9

Highlights - Consideration and vote on objections to formaldehyde in biocides - Committee on the Environment, Public Health and Food Safety - February 24, 2026

On 25 February, ENVI Members will consider and vote on objections to two Commission implementing regulations approving formaldehyde released from certain reaction products as an existing active substance for use in biocidal products.

The objectors oppose these measures on the grounds that they are not compatible with the aim and the content of the Biocidal Products Regulation. The objectors point out that the approval of the substances concerned is inappropriate and disproportionate because the Commission based its analysis of alternatives on an incomplete hazard profile, failed to consider their endocrine-disrupting properties in its evaluation, and proposed risk mitigation measures that cannot be considered binding. The objectors also argue that the regulation violates the precautionary principle and the Commission's obligation to ensure a high level of protection of human health and the environment. The objectors call on the Commission to withdraw the draft regulations.

Dendritic mixed-mode stationary phases prepared by thiol-epoxy click reaction for the determination of bisphenols in a variety of complex samples - February 23, 2026

Anal Chim Acta. 2026 Apr 8;1394:345216. doi: 10.1016/j.aca.2026.345216. Epub 2026 Feb 7.

ABSTRACT

BACKGROUND: Bisphenols are widely used in thermal paper, inks, coatings, and other fields. Among them, abnormal concentrations of bisphenol A (BPA) can disrupt the human endocrine system, making it essential to closely monitor BPA levels in environmental and daily life samples. Owing to its strong separation and analytical capabilities, high performance liquid chromatography (HPLC) enables accurate analysis of compounds in complex real-world samples. Among various HPLC stationary phases, dendritic stationary phase materials have attracted significant attention due to their unique branched spatial structure. Therefore, it is of great research importance to continuously investigate dendritic HPLC stationary phases, expand their variety, and broaden their applications.

RESULTS: The novel dendrimer based stationary phase named as Sil-G1-BDDE-TTCA was synthesized by modifying 1,4-butanediol diglycidyl ether and trithiocyanuric acid onto silica surfaces via thiol-epoxy click reaction. Through three repeated grafting, the third-generation stationary phase named as Sil-G3-BDDE-TTCA was prepared. The C18 modified dendrimer based stationary phase named as Sil-G3-BDDE-TTCA-C18 was finally prepared using 1-octadecene as a capping functional monomer. These dendritic stationary phases were characterized by Elemental analysis, Thermogravimetric analysis, Scanning electron microscope and X-ray photoelectron spectroscopy. To evaluate the hydrophobic, hydrophilic, and π-π interactions of the prepared dendritic stationary phases, test mixtures including alkylbenzenes, positional isomers, polycyclic aromatic hydrocarbons, nucleosides, and flavonoids were analyzed. The Tanaka test was employed to compare the chromatographic performance of different stationary phases. Thermodynamic parameters for the retention of alkylbenzenes and positional isomers on these stationary phases were calculated to investigate the effect of temperature on chromatographic behavior. The reproducibility of these prepared dendritic columns was investigated, yielding satisfactory results.

SIGNIFICANCE: For the first time, a dendritic mixed-mode stationary phase was fabricated via thiol-epoxy click reaction for detecting bisphenols in actual samples. This strategy overcomes the time-consuming and inefficient synthesis of traditional dendritic phases, offering a novel route for dendritic materials and extending their environmental applications.

PMID:41730599 | DOI:10.1016/j.aca.2026.345216

Bisphenols and Phthalates in Bottled Mineral Water: First Evidence of Co-Occurrence, Estrogenic Activity, and Health Risk in Brazil - February 23, 2026

Environ Toxicol. 2026 Feb 23. doi: 10.1002/tox.70063. Online ahead of print.

ABSTRACT

Bisphenol A (BPA), its structural analogs, and phthalates are synthetic chemicals widely used, with documented endocrine-disrupting activity. This study aimed to develop and validate a selective multiresidue analytical method for the simultaneous determination of BPA, 10 bisphenol analogs, and six phthalates in PET-bottled mineral water. To our knowledge, this is the first report assessing the co-occurrence of these contaminants in bottled mineral water in Brazil. Six commercial bottled water brands were sampled under two storage conditions: ambient temperature and solar exposure. Solid-phase extraction (SPE) was applied before GC-MS analysis. Among the 17 target analytes, BPA, BPF, BPS, and DIOP were detected in quantifiable concentrations. BPF and DIOP were found in all samples, with maximum concentrations of 7.92 and 3.85 μg L^-1, respectively. BPA and BPS were detected in specific brands only after sunlight exposure, reaching up to 7.10 and 9.08 μg L^-1, respectively. Despite concentrations being below current international regulatory limits, health risk assessment revealed that the estimated daily intake (EDI) of BPF and BPS resulted in safety factors (SF) below 1 for both adults and children, indicating a potential health concern. Estrogen equivalency (EEQ) values associated with BPA, BPF, BPS, and DIOP ranged from 0.5 to 13 ng E₂/L, exceeding effect-based trigger values proposed for estrogenic activity in bottled mineral water. The results suggest that even BPA-free labeled packaging may pose a risk due to the presence of its analogs and highlight the need for expanded regulatory oversight and routine monitoring of endocrine-disrupting compounds in bottled water.

PMID:41731303 | DOI:10.1002/tox.70063

Molecular mimicry in the agroecosystem: A new paradigm for understanding how pesticide residues drive the emergence of antimicrobial resistance - February 23, 2026

Environ Toxicol Pharmacol. 2026 Feb 21;123:104974. doi: 10.1016/j.etap.2026.104974. Online ahead of print.

ABSTRACT

Antimicrobial resistance (AMR) is a mounting global crisis, with environmental dissemination of antibiotic resistance genes (ARGs) emerging as a critical driver. Agroecosystems, chronically exposed to complex mixtures of bioactive chemicals, including pesticides, represent an underrecognized hotspot for AMR evolution. This review synthesizes established mechanisms by which pesticides select for resistance and introduces a novel hypothesis: molecular mimicry as a hidden driver. Evidence highlights three key pathways: cross-resistance via multidrug efflux pumps; coselection on mobile genetic elements; and enhanced horizontal gene transfer under pesticide-induced stress. Structural similarities may cause bacterial defense systems to misidentify pesticide molecules as antimicrobial threats, triggering resistance responses analogous to endocrine disruption by xenoestrogens such as BPA and DDT. Case studies on macrolides and ivermectin illustrate this concept, as both share macrocyclic lactone scaffolds with insecticides like spinosyns. This framework positions pesticide pollution as a central contributor to AMR, underscoring the need for One Health-based regulatory reform.

PMID:41730359 | DOI:10.1016/j.etap.2026.104974

Raising environmental awareness: evaluating microplastic education interventions in Jakarta's high schools - February 23, 2026

Int J Adolesc Med Health. 2026 Feb 25. doi: 10.1515/ijamh-2025-0231. Online ahead of print.

ABSTRACT

OBJECTIVES: Microplastics have emerged as a growing environmental and public health concern, found in air, water, and food, with potential health impacts including respiratory, digestive, and endocrine disruption. Therefore, the preventive effort needs to be amplified. This study aimed to evaluate the effectiveness of three different microplastic education interventions, lecture-based education, peer group education, and infographic distribution, among high school students in DKI Jakarta.

METHODS: A quasi-experimental design was employed involving 334 students from six schools, with pre- and post-intervention assessments of knowledge and attitudes. Data were analyzed using the Wilcoxon Signed-Rank Test and Kruskal-Wallis Test, followed by Dunn's post hoc test.

RESULTS: Findings revealed that peer group and infographic interventions significantly improved knowledge scores, with the peer group showing the most substantial gains. However, lecture-based education did not yield significant improvement in knowledge. Attitude changes across all interventions were not statistically significant, although numerical improvements were observed, especially in the peer group. The Kruskal-Wallis test indicated significant differences in knowledge improvement across groups (p=0.0041), and Dunn's test confirmed a statistically significant difference between peer group and lecture-based education.

CONCLUSIONS: The results suggest that interactive and peer-driven educational approaches may be more effective in enhancing students' understanding of microplastic pollution compared to traditional lectures. However, attitude change may require more prolonged or multifaceted interventions that integrate psychosocial and behavioral elements. Given the formative nature of adolescence and their potential as agents of environmental change, incorporating targeted and participatory education into school curricula is essential. These findings underscore the importance of using context-specific, engaging methods for environmental health education, contributing to the achievement of Sustainable Development Goals (SDGs), particularly SDG 12 and SDG 13.

PMID:41730020 | DOI:10.1515/ijamh-2025-0231

Exposure to a low dose mixture of endocrine disrupting chemicals alters the brain transcriptome and animal behavior - February 23, 2026

bioRxiv [Preprint]. 2026 Feb 11:2026.02.10.705055. doi: 10.64898/2026.02.10.705055.

ABSTRACT

Exposures to pervasive chemical toxicants such as endocrine disrupting chemicals (EDCs) are associated with adverse neurological and neurodevelopmental deficits. Although EDCs are widespread as sparse mixtures in the environment, most research has focused on single chemicals at high concentrations. Here, we studied the effects of ldEDC: a low-dose mixture of widely prevalent toxicants at doses representative of normal human exposure levels. Primary cultured mouse neurons treated with ldEDC exhibited altered gene expression compared to vehicle controls in genes critical for neuron activity, indicating low doses EDCs can affect neuronal function directly. We next tested persistent exposure through the maternal diet to define perinatal effects on offspring. Exposed offspring exhibited differences in development, tactile sensitivity, and sex-specific changes in motor behavior. Cortical single-nuclei sequencing identified broad transcriptomic changes, particularly in distinct cortical layer subpopulations, excitatory neurons, and astrocytes. Cell-cell signaling between neurons and non-neuronal populations were altered in exposed mice, specifically in pathways associated with cellular adhesion. Transcriptomic differences were also sex-specific. Together, these in vitro and in vivo findings reveal molecular and phenotypic consequences of EDC exposure at a mixture of doses well below commonly studied levels and highlights common functional pathways of susceptibility.

PMID:41727105 | PMC:PMC12918856 | DOI:10.64898/2026.02.10.705055

Raising environmental awareness: evaluating microplastic education interventions in Jakarta's high schools - February 23, 2026

Int J Adolesc Med Health. 2026 Feb 25. doi: 10.1515/ijamh-2025-0231. Online ahead of print.

ABSTRACT

PMID:41730020 | DOI:10.1515/ijamh-2025-0231

Biochar for the adsorption of endocrine-disrupting chemicals: performance, mechanisms, and strategies - February 23, 2026

RSC Adv. 2026 Feb 20;16(12):10310-10335. doi: 10.1039/d5ra08986g. eCollection 2026 Feb 20.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) in the environment can interfere with the normal levels of hormones in human bodies, posing threats to human health. Hence, the removal of EDCs is an urgent matter. Biochar, recognized as a low-cost and eco-friendly adsorbent, possesses significant potential for removing EDCs. In recent years, numerous studies have reported on the adsorption of pollutants by biochar. However, a systematic summary specifically addressing the adsorption of EDCs by biochar remains absent. This review addresses this gap by providing the first comprehensive synthesis of biochar applications in the adsorption of EDCs, introducing a novel modular design strategy which is proposed herein for the first time to tailor biochar properties to target EDC structures. This article initially summarizes and analyzes the preparation and modification methods of biochar. Secondly, a discussion is conducted regarding the analysis of various types of EDCs adsorbed by biochar. Based on the mechanism by which biochar absorbs EDCs, a modular design strategy for biochar is first proposed. Additionally, the main influencing factors and economic feasibility of biochar removal for EDCs are deliberated. Finally, prospects for future research on biochar removal of EDCs are presented.

PMID:41725828 | PMC:PMC12922941 | DOI:10.1039/d5ra08986g

Sex hormone-psoriasis interactions: from sex-specific clinical features to immunoregulatory mechanisms - February 23, 2026

Front Immunol. 2026 Feb 6;17:1731024. doi: 10.3389/fimmu.2026.1731024. eCollection 2026.

ABSTRACT

Psoriasis is a chronic inflammatory skin disease mediated by T cells, characterized by distinct sex differences and variations across different reproductive stages, suggesting that sex hormones may play a significant role in its pathogenesis. In recent years, research has increasingly focused on the bidirectional effects of sex hormones in psoriasis: on one hand, changes in hormone levels can affect the onset and progression of psoriasis; on the other hand, the systemic inflammation of psoriasis can interfere with the homeostasis of the sex hormone axis. This review systematically integrates clinical epidemiological evidence of sex hormone abnormalities in cutaneous psoriasis patients, outlines the molecular mechanisms of estrogen, androgen, and progesterone in immune-inflammatory regulation of psoriasis, and further explores how psoriasis-related inflammation, through cytokines, stress responses, and metabolic abnormalities, can in turn disrupt sex hormone balance. The focus is primarily on immunopathological mechanisms, with a secondary consideration of the impact of metabolic and stress-related factors, which modulate immune responses and may indirectly influence disease progression. We highlight the complex immune-endocrine network interaction between sex hormones and cutaneous psoriasis, emphasizing the need for future sex-stratified studies, dynamic hormone monitoring, and mechanistic validation models to clarify their causal pathways. This will aid in understanding the sex-specific clinical manifestations of psoriasis and provide a theoretical basis for developing hormone-targeted intervention strategies.

PMID:41727453 | PMC:PMC12920573 | DOI:10.3389/fimmu.2026.1731024

Exploratory assessment of preconception phthalate exposure on pregnancy and offspring health outcomes in mice - February 23, 2026

J Endocr Soc. 2026 Jan 23;10(3):bvag010. doi: 10.1210/jendso/bvag010. eCollection 2026 Mar.

ABSTRACT

Understanding how endocrine-disrupting chemicals influence reproductive success requires attention to sensitive windows beyond gestation, including the understudied preconception period. In this exploratory pilot study, female CD-1 mice were exposed to a human-relevant phthalate mixture (200 µg/kg/day) for 30 days prior to mating. Although implantation and litter size were unaffected, exposed dams exhibited nonsignificant shifts in estrus cyclicity, spending more time in proestrus and less in metestrus. Maternal liver transcriptomics revealed persistent changes more than a month after exposure ceased, with differential expression of genes involved in mitochondrial metabolism, oxidative phosphorylation, and xenobiotic processing, suggesting long-term metabolic reprograming in the absence of overt toxicity. Maternal effects coincided with developmental alterations at mid-gestation. At E14.5, fetuses from exposed dams were heavier, and placentas displayed expansion of the junctional zone, a region critical for endocrine function. This early growth enhancement reversed later in life, as exposed male offspring exhibited reduced adult body weight, consistent with altered developmental programing. Transcriptomic profiling revealed pronounced sex-specific placental responses: female placentas exhibited extensive reprograming across immune, metabolic, and extracellular matrix pathways (518 differentially expressed genes [DEGs]), whereas male placentas showed minimal differential expression (9 DEGs), despite enrichment for RNA processing and mitochondrial pathways. Adult offspring livers also displayed sex-specific transcriptional signatures, with exposed females downregulating metabolic and immune-regulatory genes and exposed males upregulating inflammatory pathways. Collectively, these hypothesis-generating findings provide early evidence that preconception exposures can shape maternal physiology, placental development, and long-term offspring health, highlighting the preconception period as a critical yet understudied window of susceptibility.

PMID:41728212 | PMC:PMC12922444 | DOI:10.1210/jendso/bvag010

Sensing element design in optical pesticide-detecting arrays - February 23, 2026

Anal Methods. 2026 Feb 23. doi: 10.1039/d5ay01971k. Online ahead of print.

ABSTRACT

The escalating global reliance on synthetic pesticides to secure agricultural productivity has intensified concerns over their adverse impacts on human health and ecosystems. With pesticide exposure linked to severe pathologies-including neurotoxicity, endocrine disruption, and carcinogenesis-there is an urgent need for rapid, sensitive, and field-deployable monitoring tools. Conventional analytical methods such as gas or liquid chromatography coupled with mass spectrometry offer high accuracy but are impractical for on-site, real-time screening due to their cost, complexity, and infrastructure demands. In response, optical (bio)sensor arrays have emerged as powerful alternatives that mimic biological sensory systems by generating multidimensional response patterns (analyte-specific fingerprints) from ensembles of cross-reactive sensing elements. This review provides a comprehensive and mechanism-driven analysis of the key sensing element classes used in these arrays for pesticide detection, including label-free plasmonic nanoparticles, chemosensors, host-guest systems, enzymes, antibodies, and aptamers. This review critically evaluates the operational principles, recent advances, practical limitations, and real-world applicability of each platform. By unifying diverse sensing paradigms under a common conceptual framework, this review distills key design principles from reported optical sensor arrays and provides actionable guidance for designing practical platforms to detect and discriminate pesticide residues-balancing robustness, simplicity, and scalability for real-world environmental and food safety applications.

PMID:41729128 | DOI:10.1039/d5ay01971k

Impact of polystyrene microplastic exposure at low doses on male fertility: an experimental study in rats - February 22, 2026

Sci Rep. 2026 Feb 23;16(1):7474. doi: 10.1038/s41598-026-38385-y.

ABSTRACT

Polystyrene microplastics (PS-MPs), widely used in commercial and pharmaceutical products, are emerging endocrine-disrupting pollutants with potential reproductive toxicity. This study evaluated the dose-dependent effects of PS-MPs on adult male rats by assessing semen quality, reproductive hormones, oxidative stress, mitochondrial and inflammatory markers, and testicular histology. Rats were assigned to six groups: a control group and five groups receiving PS-MPs orally (0.1, 1, 10, 20, or 40 µg/kg BW) for 45 days. PS-MP exposure reduced sperm count and motility, increased abnormal sperm, decreased testosterone, and elevated FSH and LH. Mitochondrial biogenesis/function markers (PGC-1α, UCP1, TFAM) were downregulated, while NF-κB, caspase-3, and TBARS were increased, accompanied by significant depletion of antioxidant defenses (GSH, GR, GPx, SOD, GST, CAT, TAC) and pronounced testicular histopathology. These effects were dose-dependent, and PS-MPs were detected in testicular tissue by pyrolysis-GC/MS at the doses of 10 µg/kg and higher. Collectively, the data identify mitochondrial dysfunction-driven oxidative stress and associated inflammation as a key mechanism by which PS-MPs induce spermatogenic failure, hormonal disruption, and testicular damage, highlighting their potential as potent male reproductive toxicants.

PMID:41724789 | PMC:PMC12929567 | DOI:10.1038/s41598-026-38385-y

Impact of polystyrene microplastic exposure at low doses on male fertility: an experimental study in rats - February 22, 2026

Sci Rep. 2026 Feb 23;16(1):7474. doi: 10.1038/s41598-026-38385-y.

ABSTRACT

PMID:41724789 | PMC:PMC12929567 | DOI:10.1038/s41598-026-38385-y

Placental Small Extracellular Vesicles as Modulators of Bisphenol A-Induced Oxidative Stress and Mitochondrial Activation in Human Astrocytoma Cells (U-373 MG) - February 21, 2026

Am J Physiol Cell Physiol. 2026 Feb 21. doi: 10.1152/ajpcell.00312.2025. Online ahead of print.

ABSTRACT

Astrocytes play a crucial role in maintaining central nervous system (CNS) homeostasis, supporting neuronal function and regulating oxidative stress. The placenta, through the secretion of small extracellular vesicles (sEVs), facilitates communication between the maternal and fetal environments, potentially mitigating external stressors. Bisphenol A (BPA), an endocrine disruptor, has been implicated in oxidative stress and mitochondrial dysfunction, particularly in the developing brain. However, the mechanisms by which placental sEVs influence astrocyte responses to BPA remain unclear. This study investigates the effects of BPA on astrocyte oxidative stress and mitochondrial activity and explores how placental sEVs modulate these responses. Human glioblastoma astrocytoma (U-373 MG) cells were exposed to environmentally relevant concentrations of BPA (10 nM), with or without placental sEVs isolated from human term placental explants. Reactive oxygen species (ROS) levels, mitochondrial activation, and antioxidant enzyme expression (SOD1, GCLC, GSTA) were assessed. Direct BPA exposure increased astrocyte ROS levels and mitochondrial activation, indicative of oxidative stress. Placental sEVs were rapidly internalized by astrocytes and counteracted BPA-induced ROS accumulation, restoring mitochondrial homeostasis. Notably, sEVs from BPA-exposed placental explants were more efficiently incorporated into astrocytes, suggesting an adaptive response. sEVs treatment also upregulated antioxidant enzyme expression and reduced inflammatory cytokine markers (CCL2, IL-1β), indicating a potential protective mechanism. These findings suggest that placental sEVs play a critical role in modulating astrocyte responses to oxidative stress and mitochondrial dysfunction. The ability of sEVs to restore redox homeostasis highlights their potential physiological function in fetal neuroprotection against environmental stressors.

PMID:41721783 | DOI:10.1152/ajpcell.00312.2025

Platelet mitochondrial DNA methylation mediates the association of bisphenol, phthalate, and paraben exposures with type 2 diabetes mellitus: An exploratory nested case-control study - February 21, 2026

Ecotoxicol Environ Saf. 2026 Feb 20;312:119908. doi: 10.1016/j.ecoenv.2026.119908. Online ahead of print.

ABSTRACT

Exposure to environmental pollutants has been found to be associated with epigenetic modifications of platelet mitochondria, which may influence the risk of type 2 diabetes mellitus (T2DM). However, research on the relationship between exposure to environmental endocrine disrupting chemicals (EDCs) and T2DM remains very limited at the molecular level of mitochondrial epigenetic alterations. This study aims to investigate the impact of mixed exposure to bisphenols (BPs), phthalates (PAEs), and parabens (PBs) on T2DM and platelet mitochondrial DNA (mtDNA) methylation, using a nested case-control study design. Levels of BPs, PAEs, and PBs metabolites were quantified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). We used weighted quantile sum (WQS) and bayesian kernel machine regression (BKMR) models to assess the association between individual and mixed exposure to multiple EDCs and T2DM. Methylation levels of mitochondrial coding genes were measured by bisulfite pyrosequencing. In logistic regression models, MT-COX1 methylation levels were significantly negatively associated with T2DM risk, whereas MT-COX3 methylation levels were significantly positively associated. Both WQS and BKMR models indicated that mixed exposure to BPs, PAEs, and PBs was positively linked to T2DM, with DnPrP and DEHP identified as the primary contributors. Mediation analysis demonstrated that MT-COX3 methylation significantly mediated the associations of DEP, DMP, DEHP, DnPrP, DAlP, and MP with T2DM. Our findings indicate that both individual and mixed exposure to PAEs and PBs are positively associated with T2DM risk. Platelet mtDNA methylation mediates the association between EDCs exposure and T2DM risk, suggesting its potential utility as a biomarker.

PMID:41722352 | DOI:10.1016/j.ecoenv.2026.119908

Binding interactions of Trametes villosa and Trametes lactinea laccases with 4-nonylphenol and its intermediates: molecular docking and molecular dynamics approaches - February 20, 2026

Environ Sci Pollut Res Int. 2026 Feb 20. doi: 10.1007/s11356-026-37475-8. Online ahead of print.

ABSTRACT

Emerging pollutants such as 4-nonylphenol (4-NP) act as endocrine disruptors and have been associated with reproductive toxicity in humans and wildlife, as well as with physiological disturbances in aquatic, terrestrial, and plant organisms. Laccases are oxidoreductases with notable biotechnological relevance and the ability to oxidize phenolic pollutants, making them attractive candidates for biodegradation strategies. This study investigated the interactions between laccases from Trametes villosa and Trametes lactinea and 4-NP and its degradation intermediates via molecular docking and molecular dynamics simulations (MDS). Ligands were geometrically optimized using the PM7 semiempirical method, and their global reactivity descriptors were computed to explore correlations between electronic properties and laccase binding affinity. Docking revealed favorable binding energies (ΔG_bind ≈ -6 kcal·mol^-1) and recurrent interactions with key amino acid residues, including Ala, Glu, Leu, Phe, Pro, Ser, Val, and His, mainly through hydrogen bonding and hydrophobic contacts. The MDS confirmed the stability of the enzyme-ligand complexes, as indicated by low root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, along with consistent radius of gyration and solvent-accessible surface areas throughout the trajectories. Binding free energy calculations using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method indicated stronger binding affinity under solvation, with ΔG_bind values of -26.45 and -17.73 kcal·mol^-1 for T. villosa and T. lactinea, respectively, highlighting hydrophobic and van der Waals contributions as the primary stabilizing forces. Overall, these results provide computational evidence that laccases from T. villosa and T. lactinea have potential for application in the oxidative biodegradation of 4-NP. These findings advance the molecular understanding of fungal laccase‒pollutant interactions and support future in vitro validation and protein engineering strategies aimed at enhancing biodegradation efficiency.

PMID:41719001 | DOI:10.1007/s11356-026-37475-8

Foam Cushing: endocrine disruption from excessive hygiene zeal - February 20, 2026

J Endocrinol Invest. 2026 Feb 20. doi: 10.1007/s40618-026-02840-4. Online ahead of print.

NO ABSTRACT

PMID:41719004 | DOI:10.1007/s40618-026-02840-4

Reproductive Impact of Natural, Synthetic and Emerging Chemicals on Wildlife and Domestic Animals - February 20, 2026

Adv Exp Med Biol. 2026;16:167-208. doi: 10.1007/978-3-031-87707-0_6.

ABSTRACT

Wildlife and domesticated animals are exposed to a wide range of natural and synthetic chemicals throughout their life span. Many of these chemicals possess endocrine-disrupting properties which have the potential to disrupt reproductive and developmental process in certain animals. Organochlorine compounds, used as pesticides or in industrial and consumer products in the 1950s, were one of the earliest examples of synthetic endocrine-disrupting chemicals to be linked with adverse reproductive effects in animals. These legacy chemicals have since been restricted for use but continue to persist in the environment and threaten reproductive health of top predators, including porpoises, dolphins and whales. Newer chemicals, including some that were made to replace legacy chemicals and in use today, have been reported to also have endocrine-disrupting properties. These chemicals are manufactured for a wide range of uses, covering a broad range of chemically diverse substances, which include brominated flame retardants, plasticizers and pharmaceutically active ingredients among many other classes of chemicals. When present in the environment, they have been collectively termed emerging contaminants and have been linked with many adverse effects in animals, including impairments in reproduction and development. Whilst exposure to individual chemicals receives regular regulatory interest, there remains a particular concern about wildlife exposures to cocktails of endocrine-disrupting chemicals, which, combined with other stressors, may play a significant role in reproductive disorders that cannot be reproduced in laboratory experiments with single- or multi-chemical exposures. Regulation of chemicals, including restriction on the use of some chemicals, affords some protection to animals of the adverse effects of exposure to some EDCs, but there are presently no specific regulations on a holistic cross-government discharge limit for EDCs into the environment that would significantly reduce or eliminate animal exposure to EDCs.

PMID:41718871 | DOI:10.1007/978-3-031-87707-0_6

How to Ensure a Bright Future for Reproductive Sciences in Animal Conservation - February 20, 2026

Adv Exp Med Biol. 2026;16:647-656. doi: 10.1007/978-3-031-87707-0_19.

ABSTRACT

The chapters in this book emphasize the critical role that reproductive sciences play in wildlife conservation, highlighting the significant progress that has been made since the first edition was published a decade ago. While initially, there was significant excitement around technologies like cloning and bringing animals back from extinction, practical limitations and ethical concerns have since tempered expectations. This new edition underscores that while advanced reproductive technologies can contribute to conservation, they are not standalone solutions for reversing wildlife population declines. Instead, multidisciplinary approaches that integrate environmental science, reproductive biology, and ethical considerations are essential. Key insights from these chapters include how important it is to understand the developmental origins of health and disease in wildlife, especially given how environmental stressors such as pollutants and climate change can affect reproductive success across generations. Papers also discuss the challenges posed by endocrine disruptors and microplastics, which threaten both terrestrial and aquatic species. Advances in noninvasive reproductive monitoring techniques for large marine mammals and birds are highlighted as promising tools for conservation efforts. However, one must be cognizant of ethical concerns central to conservation biology, particularly regarding the use of reproductive technologies in endangered species. The need for minimally invasive methods and more holistic experimental designs is stressed, alongside the importance of balancing scientific innovation with animal welfare. A central theme running through these chapters is the need for enhanced interdisciplinary collaboration, training programs, and public engagement to ensure that wildlife conservation efforts are sustainable and effective in the face of ongoing environmental and anthropogenic challenges.

PMID:41718884 | DOI:10.1007/978-3-031-87707-0_19

How to Ensure a Bright Future for Reproductive Sciences in Animal Conservation - February 20, 2026

Adv Exp Med Biol. 2026;16:647-656. doi: 10.1007/978-3-031-87707-0_19.

ABSTRACT

PMID:41718884 | DOI:10.1007/978-3-031-87707-0_19

Reproductive Science Methods for Marine Mammals - February 20, 2026

Adv Exp Med Biol. 2026;16:553-604. doi: 10.1007/978-3-031-87707-0_17.

ABSTRACT

Marine mammals encompass a wide array of species that have evolved specialized anatomical and physiological traits, enabling them to survive and thrive in the challenging conditions of oceanic environments which are often characterized by abiotic extremes (e.g., temperature, pressure, light) and biotic variability (e.g., food availability, distribution of conspecifics). As human activities increasingly encroach on coastal fringes and extend into even the remotest parts of the ocean, it becomes essential to understand the survival prospects of marine mammal populations. Understanding the rates at which marine mammals reproduce is vital for evaluating their capacity to endure and adapt in a rapidly changing marine world. In this chapter, we explore contemporary methodologies used to study diverse aspects of reproductive science in marine mammals, including direct observation of reproductive behavior and outcomes, endocrine assessments to determine reproductive state, and assisted reproductive technologies designed to enhance reproductive success. We emphasize the latest advances and innovations in reproductive sampling of marine mammals, noting a continuing progression towards noninvasive data collection methods that are driven by new technologies and emerging challenges. Among the most vulnerable in the world due to their unique combinations of function traits are northern right whales, Eubalaena spp., and the dugong, Dugong dugon. Here, these two case studies are presented to illustrate the challenges faced by researchers studying marine mammals in their natural habitats and to showcase the range of technical approaches employed. The North Atlantic right whale, Eubalaena glacialis, is on the brink of extinction through historical overharvest and present-day threats of entanglement and vessel collisions. Environmental disruption to their migratory routes and declining health have led to reduced reproductive rates. On the other hand, the emerging threat to the vulnerable dugong appears to be extreme weather events that affect the availability of their seagrass food sources. Climate disruption, with increasingly severe coastal storms and flooding, poses a risk to the health of coastal seagrass beds, thereby negatively impacting the reproductive success and survival of this species. It is anticipated that climate change will have varied and often severe impacts on the reproduction of marine mammal populations globally, and understanding reproduction in marine mammals has never been more critical.

PMID:41718882 | DOI:10.1007/978-3-031-87707-0_17

Sunscreens - January 1, 2006

2026 Feb 15. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–.

ABSTRACT

Sunscreen ingredients vary considerably from product to product and country to country. It is best to look for the individual sunscreen chemical(s) in a specific product than to rely on brand names. Organic chemical sunscreens are absorbed systemically when applied to human skin. Most organic chemical sunscreens are detectable in breastmilk, but the amounts that an infant would ingest are usually lower than current limits of concern.[1-5] Products containing octinoxate, enzacamene, and especially oxybenzone should probably be avoided during breastfeeding because of their possible endocrine-disrupting effects.[5,6] Inorganic mineral sunscreens containing titanium dioxide and zinc oxide may be better alternatives for nursing mothers.[6] Avoiding sun exposure during the mid-day peak ultraviolet (UV) hours, sitting in shaded areas such as under umbrellas, and wearing sun-protective clothing, such as wide-brimmed hats, long sleeves, and long pants can reduce the need for chemical sunscreens.

PMID:41730063 | Bookshelf:NBK621060