Endocrine Disruption

Front Physiol. 2026 Sep 28;17:1952582. doi: 10.3389/fphys.2026.1952582. eCollection 2026.

ABSTRACT

The endocannabinoid system (ECS) is a ubiquitous lipid signaling network that regulates tissue homeostasis. Increasing evidence indicates that the ECS undergoes profound remodeling during pancreatic injury and may influence key pathological processes underlying acute pancreatitis (AP) and chronic pancreatitis (CP). Interest in this field has grown in parallel with increasing cannabis use among individuals with pancreatic disorders and the urgent need for alternatives to opioid-based pain management. Components of the ECS, including cannabinoid receptors, the endogenous ligands, and enzymes that mobilize such ligands, are widely expressed throughout both the exocrine and endocrine pancreas, where they contribute to the regulation of pancreatic function under physiological and pathological conditions. Studies demonstrate that AP and CP are associated with distinct alterations in cannabinoid receptor expression and endocannabinoid levels, yet the functional significance of these changes remains incompletely understood. Clinical evidence, however, remains limited and often conflicting. In this narrative review, we summarize current knowledge of ECS organization and function in the pancreas, examine how endocannabinoid signaling is altered during pancreatitis, and critically evaluate the therapeutic opportunities and challenges associated with targeting ECS pathways. We discuss an emerging hypothesis in which adaptive endocannabinoid signaling may contribute to resilience following pancreatic injury and propose that progressive disruption of this response could contribute to the transition from AP to CP.

PMID:42866025 | PMC:PMC13655718 | DOI:10.3389/fphys.2026.1952582

RSC Adv. 2026 Oct 12. doi: 10.1039/d6ra03309a. Online ahead of print.

ABSTRACT

Estrogens and other steroid hormones, also known as endocrine-disrupting chemicals (EDCs), are emerging contaminants in wastewater effluent due to human activities. Although these compounds play essential roles in medical treatments and modern agriculture, their release into the environment has raised concerns because of their potential ecological and health impacts. The selective removal of EDCs from aqueous environments is a challenge due to competition with water molecules for binding sites. This work presents a systematic computational investigation of the intermolecular interactions and phase equilibria of selected EDCs and water in the presence of poly(mannuronate), a principal component of the brown-algae-derived biopolymer alginate, with the key goal of informing the design of polysaccharide-based materials for water remediation. Atomistic molecular dynamics simulations were coupled with stochastic calculations and extended off-lattice Flory-Huggins theory to assess polymer flexibility, penetrant-polymer coordination numbers, binding energies, and binary phase equilibria. To complement thermodynamic analysis, quantum chemical calculations were performed on representative low-energy configurations. Results showed that both the quantity and spatial positioning of species bound to alginate can be tuned via the relative proportions of guluronate versus mannuronate blocks constituting the polymer, providing a pathway for optimizing binding selectivity. Frontier molecular orbital analysis revealed distinct donor-acceptor characteristics for mannuronate-EDC complexes compared to mannuronate-water systems. These variations result in lower Flory-Huggins interaction parameters and enhanced thermodynamic compatibility of EDCs with the polymer matrix, suggesting preferential association in aqueous environments. Overall, this study provides molecular-level insights into the rational design of materials for the selective removal of EDCs from water systems.

PMID:42865779 | PMC:PMC13655788 | DOI:10.1039/d6ra03309a

Environ Geochem Health. 2026 Oct 13;48(16):637. doi: 10.1007/s10653-026-03540-x.

ABSTRACT

Phthalate esters (PEs), widely used as plasticizers in consumer products, are endocrine disruptors and represent a significant source of exposure for pregnant women and the fetus. This study, conducted among 198 pregnant women from middle-class backgrounds and monitored in the maternity ward in Monastir hospital (Tunisia), assessed the concentrations of several PEs in maternal and fetal biological matrices to estimate exposure levels during pregnancy. GC-MS/MS chromatographic analyses were performed on maternal samples namely, placenta, amniotic fluid, urine, and blood. Seven plasticizers, including phthalates and non-phthalates alternatives were detected namely: diisobutyl phthalate (DiBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), dimethyl phthalate (DMP), di(2-ethylhexyl) terephthalate (DEHT), diisobutyl adipate (DiBA), dimethyl adipate (DMA). DEHT, was the most prevalent plasticizer despite being a "safer" alternative, with highest geometric mean concentration in urine (403.7 µg/kg), followed by placenta (318.6 µg/kg), blood (304.5 µg/kg), and amniotic fluid (275.0 µg/kg). Among phthalates, DiBP showed the highest concentrations in placental tissue (195.8 µg/kg) and urine (226.0 µg/kg), while DMP and DEP were mainly detected in amniotic fluid (128.2 and 64.8 µg/kg, respectively). Although the renal system contributes significantly to the elimination of these substances via urine, substantial amounts can cross the placental barrier and reach the fetus, thus posing a potential health risk. the findings highlight a clear maternal-fetal exposure continuum to PEs and underline the need for improved exposure control, especially for vulnerable populations, and support further evaluation of both PEs and their substitutes.

PMID:42867580 | DOI:10.1007/s10653-026-03540-x

Hypertens Pregnancy. 2026 Dec 31;45(1):2742300. doi: 10.1080/10641955.2026.2742300. Epub 2026 Oct 13.

ABSTRACT

Hypertensive disorders of pregnancy (HDP) encompass chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension, affecting about 5% to 10% of pregnancies worldwide and remaining a major cause of maternal and perinatal morbidity and mortality. Their burden is increasing with rising obesity, advanced maternal age, evolving diagnostic criteria, and marked socioeconomic and racial-ethnic disparities. This review summarises current evidence on the epidemiology, pathophysiology, biomarkers, clinical management, and long-term outcomes of HDP, highlighting recent advances and unresolved questions. Mechanistically, HDP is characterised by systemic endothelial dysfunction and angiogenic imbalance, particularly involving soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng), together with immune maladaptation, oxidative stress, and genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs) and sleep-disordered breathing (SDB). The sFlt-1/PlGF ratio is among the most validated tools for short-term risk assessment in suspected preeclampsia, while retinal microvascular imaging may provide a non-invasive marker of systemic microvascular dysfunction. Clinically, trial evidence supports treating mild chronic hypertension to below 140/90 mmHg to reduce adverse outcomes without compromising foetal growth. Long-term maternal cardiovascular and metabolic risks vary according to HDP phenotype, severity, gestational age at onset, and associated preterm delivery or foetal growth restriction, whereas offspring neurodevelopmental associations are largely observational and may be influenced by prematurity and shared familial or socioeconomic factors. Experimental strategies supported primarily by preclinical or early translational evidence include PPARγ agonists, placenta-targeted nanomedicine, and transcutaneous auricular vagus nerve stimulation. Machine learning combined with longitudinal multi-omics data may support precision risk stratification and individualised management.

PMID:42867037 | DOI:10.1080/10641955.2026.2742300

Se Pu. 2026 Oct;44(10):1175-1189. doi: 10.3724/SP.J.1123.2025.12010.

ABSTRACT

Recently， magnetic microporous organic networks （MMONs） have emerged as a novel class of adsorbents in magnetic solid-phase extraction （MSPE）. By integrating the unique properties of microporous organic networks （MONs） and magnetic nanoparticles， MMONs exhibit advantages such as designable structures， facile synthesis， diverse architectures， high specific surface area， and excellent stability， garnering widespread attention in the field of sample pretreatment. The current strategies for preparing MMONs mainly include in-situ growth， post-synthetic modification （PSM）， and composite preparation. Among these， the in-situ growth method can be further categorized into direct in-situ growth， indirect in-situ growth， and co-doping methods. The direct in-situ growth method is straightforward to operate， enabling the construction of MMONs with well-defined core-shell structures. It also allows flexible control over the functionality and shell thickness of MMONs by adjusting the type and concentration of monomers， making it the most commonly used preparation method for MMONs. In contrast， the indirect in-situ growth method involves the introduction of an intermediate bridging layer， which complicates the synthesis process. However， the intermediate coating layer and the MONs shell can work synergistically to enhance the extraction efficiency of MMONs for targets. Although PSM requires additional reaction steps and poses challenges in controlling the modification rate and distribution of functional groups， it increases the variety and quantity of modifying groups and molecules， thereby expanding the application range of MMONs in MSPE. Furthermore， MMON composites can integrate the respective advantages of both MMONs and polymers， further broadening the applicability of MMONs. Therefore， each of the three methods mentioned above has its own advantages and disadvantages. Researchers can select the appropriate synthesis method based on the specific requirements of MSPE to prepare the desired MMONs. This review also provides a detailed discussion on the applications of MMONs in the MSPE of various organic pollutants， including pharmaceuticals， pesticides， endocrine-disrupting chemicals， mycotoxins， food additives， and per- and polyfluoroalkyl substances， and elucidates the extraction mechanisms （e.g. hydrophobic interaction， π-π stacking， electrostatic attraction， hydrogen-bonding interaction， ion pair interaction， fluorine-fluorine interaction， and π-CF interaction） between MMONs and analytes. In response to the current challenges of MMONs， future research should focus on the following areas： （1） Designing and expanding low-cost functional monomers to enrich the variety and quantity of existing functional monomers， providing other effective PSM methods for synthesizing functionalized MMONs， and introducing other functional composites to prepare MMON composites. （2） Developing target-oriented structural design or functionalization strategies to construct functionalized MMONs， with the aim of improving their selectivity toward specific targets. （3） Advancing other advanced characterization and mechanism investigation techniques to understand the extraction mechanisms of MMONs and guide their structural design or functionalization. In summary， this review aims to deepen the understanding of MMONs-based MSPE methods in the enrichment and detection of various organic pollutants， while offering guidance for the synthesis and application of MMONs.

PMID:42865165 | PMC:PMC13659867 | DOI:10.3724/SP.J.1123.2025.12010

Fish Shellfish Immunol. 2026 Oct 13:111780. doi: 10.1016/j.fsi.2026.111780. Online ahead of print.

ABSTRACT

Systemic fungicides are widely used in modern agriculture and are increasingly detected in aquatic environments, raising concerns about their potential effects on non-target aquatic organisms. Unlike conventional toxicological studies that primarily focus on acute toxicity, oxidative stress, or organ damage, emerging evidence suggests that sublethal fungicide exposure may also disturb immune regulation and compromise host defense. This review systematically summarizes the environmental occurrence and biological effects of major systemic fungicides, including triazoles, strobilurins, benzimidazoles, and other systemic fungicides, in aquatic animals. Available evidence indicates that fungicide exposure can induce developmental and organ-specific toxicity, disrupt barrier integrity, alter immune-related responses, and interfere with cellular processes involved in immune regulation, including oxidative balance, mitochondrial function, endocrine signaling, and energy metabolism. Importantly, these effects differ in their relevance to host immunity: general physiological toxicity and changes in individual immune biomarkers should not be considered equivalent to functional immune impairment. Recent studies provide direct evidence that azoxystrobin and trifloxystrobin can impair antiviral defense and increase susceptibility to rhabdovirus infection in fish, whereas comparable pathogen-challenge evidence for other fungicides, pathogens, and aquatic animal taxa remains limited. Based on these findings, we propose immune homeostasis as a conceptual link between systemic fungicide exposure and altered host defense, and highlight the need to integrate environmentally realistic exposure, functional immune endpoints, mechanistic validation, and pathogen-challenge models into aquatic immunotoxicology. This immune homeostasis-centered perspective may improve the assessment of disease-related risks associated with chronic fungicide exposure and provide a basis for understanding how environmental chemical stress contributes to disease susceptibility in aquatic animals.

PMID:42869262 | DOI:10.1016/j.fsi.2026.111780

Environ Res. 2026 Oct 13:125878. doi: 10.1016/j.envres.2026.125878. Online ahead of print.

ABSTRACT

Exposure to environmental pollutants and endocrine-disrupting chemicals (EDCs) in early life is a critical public health issue because it can alter developmental programming that impacts susceptibility to disease throughout life. The prenatal and early postnatal periods are times of vulnerability when exposure to environmental stressors may impact endocrine signalling, placental function, epigenetic regulation, and metabolic homeostasis. There is increasing evidence that exposure to bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), pesticides, heavy metals, and air pollutants has been associated with pregnancy outcomes, neurodevelopmental disorders, metabolic dysfunction, endocrine abnormalities and reproductive impairments. Exposomics, high-resolution mass spectrometry, biomonitoring, and passive sampling technologies have made crucial advances in characterising complex environmental exposures. At the same time, novel methods such as multi-omics, single-cell sequencing, spatial biology and microbiome studies have yielded more detailed mechanistic understanding of how environmental factors can impact developmental processes via epigenetic, inflammatory, oxidative stress, and endocrine pathways. The placenta has emerged as a valuable biomarker matrix for assessing fetal exposure and developmental programming. Exposure routes, biomonitoring methods, placental processes, molecular and epigenetic modifications, and the impacts of early-life environmental exposures on neurodevelopment, metabolism, endocrine function, and reproduction are all summarised in this review. It also emphasises current advancements in exposure assessment, preventive measures, and policy frameworks, highlighting the importance of life-course perspectives and environmental justice. To identify important windows of susceptibility, improve risk assessment, and develop strategies to safeguard maternal and child health, exposomics in conjunction with systems biology and longitudinal epidemiological approaches will be essential.

PMID:42869363 | DOI:10.1016/j.envres.2026.125878

Reprod Toxicol. 2026 Oct 13;146:109377. doi: 10.1016/j.reprotox.2026.109377. Online ahead of print.

ABSTRACT

Placental angiogenic biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio, are indicators of placental vascular health and are implicated in adverse pregnancy outcomes such as preeclampsia and preterm birth. Exposure to environmental toxicants, including air pollutants, metals and trace elements, per- and polyfluoroalkyl substances (PFAS), and endocrine-disrupting chemicals (EDCs), are increasingly recognized as contributors to placental dysfunction; however, their effects on angiogenic biomarkers remain unclear. This integrative review synthesized evidence on these relationships using Whittemore and Knafl's framework. Literature searches in PubMed, CINAHL, and EMBASE (October-November 2025; Search B updated May 2026) identified 129 articles from Search A and 452 from Search B. After duplicate removal and title/abstract screening, 35 and 37 articles, respectively, underwent full-text review. Following full-text screening and removal of overlap, 19 human studies were included. Exposure to air pollutants (PM₂.₅, NO₂, O₃, PM₁₀) predominantly demonstrated anti-angiogenic patterns, including elevated sFlt-1 or sFlt-1/PlGF ratios and reduced PlGF. Metal and trace element findings were heterogeneous, though cadmium and copper were associated with increased sFlt-1 and decreased PlGF, while lead showed no consistent association. Exposure to PFAS was associated with elevated sFlt-1 and reduced PlGF, and EDCs demonstrated anti-angiogenic trends. Overall, 14 of 19 studies reported at least one association between environmental toxicants and angiogenic biomarkers consistent with an anti-angiogenic pattern, although several studies also reported null or opposing associations. Exposure to environmental toxicants may disrupt placental angiogenic balance, highlighting potential pathways for early risk identification and prevention of adverse pregnancy outcomes.

PMID:42869196 | DOI:10.1016/j.reprotox.2026.109377

Environ Res. 2026 Oct 13:125878. doi: 10.1016/j.envres.2026.125878. Online ahead of print.

ABSTRACT

Exposure to environmental pollutants and endocrine-disrupting chemicals (EDCs) in early life is a critical public health issue because it can alter developmental programming that impacts susceptibility to disease throughout life. The prenatal and early postnatal periods are times of vulnerability when exposure to environmental stressors may impact endocrine signalling, placental function, epigenetic regulation, and metabolic homeostasis. There is increasing evidence that exposure to bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), pesticides, heavy metals, and air pollutants has been associated with pregnancy outcomes, neurodevelopmental disorders, metabolic dysfunction, endocrine abnormalities and reproductive impairments. Exposomics, high-resolution mass spectrometry, biomonitoring, and passive sampling technologies have made crucial advances in characterising complex environmental exposures. At the same time, novel methods such as multi-omics, single-cell sequencing, spatial biology and microbiome studies have yielded more detailed mechanistic understanding of how environmental factors can impact developmental processes via epigenetic, inflammatory, oxidative stress, and endocrine pathways. The placenta has emerged as a valuable biomarker matrix for assessing fetal exposure and developmental programming. Exposure routes, biomonitoring methods, placental processes, molecular and epigenetic modifications, and the impacts of early-life environmental exposures on neurodevelopment, metabolism, endocrine function, and reproduction are all summarised in this review. It also emphasises current advancements in exposure assessment, preventive measures, and policy frameworks, highlighting the importance of life-course perspectives and environmental justice. To identify important windows of susceptibility, improve risk assessment, and develop strategies to safeguard maternal and child health, exposomics in conjunction with systems biology and longitudinal epidemiological approaches will be essential.

PMID:42869363 | DOI:10.1016/j.envres.2026.125878

Reprod Toxicol. 2026 Oct 13;146:109377. doi: 10.1016/j.reprotox.2026.109377. Online ahead of print.

ABSTRACT

Placental angiogenic biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio, are indicators of placental vascular health and are implicated in adverse pregnancy outcomes such as preeclampsia and preterm birth. Exposure to environmental toxicants, including air pollutants, metals and trace elements, per- and polyfluoroalkyl substances (PFAS), and endocrine-disrupting chemicals (EDCs), are increasingly recognized as contributors to placental dysfunction; however, their effects on angiogenic biomarkers remain unclear. This integrative review synthesized evidence on these relationships using Whittemore and Knafl's framework. Literature searches in PubMed, CINAHL, and EMBASE (October-November 2025; Search B updated May 2026) identified 129 articles from Search A and 452 from Search B. After duplicate removal and title/abstract screening, 35 and 37 articles, respectively, underwent full-text review. Following full-text screening and removal of overlap, 19 human studies were included. Exposure to air pollutants (PM₂.₅, NO₂, O₃, PM₁₀) predominantly demonstrated anti-angiogenic patterns, including elevated sFlt-1 or sFlt-1/PlGF ratios and reduced PlGF. Metal and trace element findings were heterogeneous, though cadmium and copper were associated with increased sFlt-1 and decreased PlGF, while lead showed no consistent association. Exposure to PFAS was associated with elevated sFlt-1 and reduced PlGF, and EDCs demonstrated anti-angiogenic trends. Overall, 14 of 19 studies reported at least one association between environmental toxicants and angiogenic biomarkers consistent with an anti-angiogenic pattern, although several studies also reported null or opposing associations. Exposure to environmental toxicants may disrupt placental angiogenic balance, highlighting potential pathways for early risk identification and prevention of adverse pregnancy outcomes.

PMID:42869196 | DOI:10.1016/j.reprotox.2026.109377

Gynecol Pelvic Med. 2026 Jul 6;9:34. doi: 10.21037/gpm-2025-1-66. eCollection 2026.

ABSTRACT

BACKGROUND AND OBJECTIVE: Pelvic floor dysfunction (PFD) is a multifactorial condition that affects a large proportion of women, compromising urogenital support and producing symptoms such as urinary incontinence (UI). The structural and functional integrity of the pelvic floor depends on coordinated interactions among muscular, hormonal, and neuroendocrine systems. Evidence indicates that circadian misalignment, particularly in women exposed to night-shift work, sleep deprivation, and endocrine disruption, can influence pelvic floor physiology through melatonin suppression, cortisol dysregulation, and inflammatory activation. This review intends to synthesize current evidence on the links between circadian rhythm disruption, hormonal imbalance, and PFD, with specific emphasis on occupational shift work as a model of chronic chronobiological stress, highlighting their integrated pathophysiological mechanisms and preventive approaches.

METHODS: We conducted a narrative literature review using PubMed, Scopus, and Web of Science covering the period from January 2020 to October 2025. Studies investigating the relationship between circadian regulation, hormonal modulation, and pelvic floor function were included. Particular attention was given to research addressing melatonin and cortisol pathways, estrogen modulation, and occupational factors such as night-shift work, sleep deprivation, and physical overload. Eligible study designs included randomized controlled trials, observational studies (cross-sectional and cohort studies), translational and experimental research, and high-quality mechanistic reviews, defined by methodological rigor, comprehensive literature synthesis, and critical appraisal of evidence.

KEY CONTENT AND FINDINGS: Circadian rhythm disruption-characterized by decreased melatonin secretion, altered cortisol levels, and increased oxidative stress-has been associated with inflammation, impaired muscle contractility, and delayed pelvic floor tissue repair. Beyond anatomical alterations, UI is increasingly recognized as a neuroimmunoendocrine disorder in which hormonal dysregulation contributes to tissue instability and loss of urethral support. Women exposed to night-shift work, sleep deprivation, or occupational overload show higher rates of involuntary urine loss, partly mediated by endocrine desynchronization and maladaptive voiding behaviors during chronically misaligned biological rhythms. Preventive measures include supervised pelvic floor physiotherapy, optimization of sleep hygiene, correction of work schedules, and local estrogen therapy when indicated. Chronobiological and immunomodulatory interventions have recently emerged as promising adjunctive strategies.

CONCLUSIONS: Management of UI should move beyond a purely mechanical perspective toward an integrated model encompassing hormonal, metabolic, and behavioral modulation. Understanding the interactions among circadian rhythms, endocrine control, and pelvic tissue physiology may open innovative avenues for prevention and treatment, promoting precision-based, holistic care in women's health.

PMID:42861008 | PMC:PMC13653771 | DOI:10.21037/gpm-2025-1-66

J Biochem Mol Toxicol. 2026 Oct;40(10):e71128. doi: 10.1002/jbt.71128.

ABSTRACT

The male reproductive system is highly vulnerable to environmental toxicants, particularly potentially toxic elements (PTEs), which represent a growing public health concern worldwide. Increasing evidence indicates that these elements impair male reproductive function through interconnected mechanisms including oxidative stress, endocrine disruption, inflammation, apoptosis, and DNA damage, resulting in impaired spermatogenesis and infertility. This review summarizes the current understanding of the major PTEs associated with male reproductive toxicity and highlights the underlying cellular and molecular mechanisms responsible for testicular injury. In addition, it discusses emerging protective and therapeutic strategies, including antioxidants, phytochemicals, nutraceuticals, chelating agents and lifestyle-based interventions that have shown potential in mitigating PTE-induced reproductive damage. A comprehensive understanding of these mechanisms and protective approaches may facilitate the development of effective preventive and therapeutic strategies to preserve male reproductive health in populations exposed to PTEs.

PMID:42860776 | PMC:PMC13655493 | DOI:10.1002/jbt.71128

Diabetes Metab Syndr Obes. 2026 Oct 7;19:636877. doi: 10.2147/DMSO.S636877. eCollection 2026.

ABSTRACT

Genetic and lifestyle factors alone cannot explain the rising global burden of type 2 diabetes mellitus (T2DM). Growing evidence implicates endocrine-disrupting chemicals (EDCs) found in plastics, pesticides, food packaging, industrial products, and contaminated water as significant environmental contributors to metabolic dysfunction. EDCs, including bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs), and heavy metals, have been associated with insulin resistance, pancreatic β-cell dysfunction, oxidative stress, mitochondrial impairment, chronic inflammation, and epigenetic modifications that collectively promote T2DM pathogenesis. The gut microbiota has emerged as a potential mediator of EDC-associated metabolic disruption, whereby chemical exposures may alter microbial diversity, disturb the Firmicutes/Bacteroidetes ratio, impair short-chain fatty acid production, decrease intestinal barrier integrity, driving metabolic endotoxemia and systemic inflammation. This narrative review examines the major EDCs associated with diabetes, their molecular and metabolic mechanisms of action, and their interactions with the gut microbiota, drawing on current experimental and epidemiological evidence. Special emphasis is placed on probiotic supplementation as an emerging therapeutic strategy targeting the EDC-gut microbiota-metabolic axis. Current evidence for probiotics in EDC-associated metabolic dysfunction is predominantly preclinical, with studies suggesting improvements in microbial homeostasis, pancreatic oxidative damage, and glucose metabolism. However, available evidence remains heterogeneous and human clinical trials specifically examining probiotic intervention in EDC-exposed populations at risk of T2DM remain absent, representing a fundamental translational gap that future research must urgently address. Advancing precision medicine approaches, integrating microbiome profiling, metabolomics, epigenetic analysis, and coordinated efforts across toxicology, clinical medicine, and public health, will be essential to reducing the growing global burden of environmentally driven type 2 diabetes.

PMID:42861307 | PMC:PMC13654283 | DOI:10.2147/DMSO.S636877

Diabetes Metab Syndr Obes. 2026 Oct 7;19:636877. doi: 10.2147/DMSO.S636877. eCollection 2026.

ABSTRACT

Genetic and lifestyle factors alone cannot explain the rising global burden of type 2 diabetes mellitus (T2DM). Growing evidence implicates endocrine-disrupting chemicals (EDCs) found in plastics, pesticides, food packaging, industrial products, and contaminated water as significant environmental contributors to metabolic dysfunction. EDCs, including bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs), and heavy metals, have been associated with insulin resistance, pancreatic β-cell dysfunction, oxidative stress, mitochondrial impairment, chronic inflammation, and epigenetic modifications that collectively promote T2DM pathogenesis. The gut microbiota has emerged as a potential mediator of EDC-associated metabolic disruption, whereby chemical exposures may alter microbial diversity, disturb the Firmicutes/Bacteroidetes ratio, impair short-chain fatty acid production, decrease intestinal barrier integrity, driving metabolic endotoxemia and systemic inflammation. This narrative review examines the major EDCs associated with diabetes, their molecular and metabolic mechanisms of action, and their interactions with the gut microbiota, drawing on current experimental and epidemiological evidence. Special emphasis is placed on probiotic supplementation as an emerging therapeutic strategy targeting the EDC-gut microbiota-metabolic axis. Current evidence for probiotics in EDC-associated metabolic dysfunction is predominantly preclinical, with studies suggesting improvements in microbial homeostasis, pancreatic oxidative damage, and glucose metabolism. However, available evidence remains heterogeneous and human clinical trials specifically examining probiotic intervention in EDC-exposed populations at risk of T2DM remain absent, representing a fundamental translational gap that future research must urgently address. Advancing precision medicine approaches, integrating microbiome profiling, metabolomics, epigenetic analysis, and coordinated efforts across toxicology, clinical medicine, and public health, will be essential to reducing the growing global burden of environmentally driven type 2 diabetes.

PMID:42861307 | PMC:PMC13654283 | DOI:10.2147/DMSO.S636877

Drug Chem Toxicol. 2026 Oct 12:1-14. doi: 10.1080/01480545.2026.2743943. Online ahead of print.

ABSTRACT

Ethinylestradiol (EE2) and levonorgestrel (LNG) are synthetic hormones widely used in contraceptives and increasingly recognized as endocrine-disrupting contaminants. Although their individual reproductive effects are documented, their combined toxicity remains poorly understood. This study evaluated the sub-chronic reproductive toxicity of EE2 and LNG, administered alone or in combination, in male Wistar rats, with emphasis on potential non-additive endocrine-disrupting interactions. Animals were orally treated with EE2 (1 µg/kg bw), LNG (5 µg/kg bw), or both for four weeks. Individual exposures caused significant alterations in testicular weight, hormone levels, oxidative stress markers, and sperm quality, whereas epididymal weight was not significantly affected. In contrast, combined exposure markedly intensified these effects, causing severe spermatogenic impairment, near-complete sperm depletion, and major histological damage in testicular tissue. This enhanced toxicity was associated with increased lipid peroxidation, reduced antioxidant defenses, and marked suppression of testosterone, FSH, and LH levels, indicating disruption of the hypothalamic-pituitary-gonadal axis. Two-way factorial analysis confirmed statistically significant EE2 x LNG interactions for testicular weight, sperm concentration, sperm motility, LH and testosterone; in each case the observed combined effect was smaller than predicted by effect addition, indicating an infra-additive rather than synergistic interaction, consistent with a floor effect at these already substantial individual effect sizes. These findings highlight the importance of assessing combined endocrine disruptor exposures, as mixture effects modify reproductive toxicity in ways not predictable from single-compound data alone.

PMID:42861945 | DOI:10.1080/01480545.2026.2743943

Anal Methods. 2026 Oct 12. doi: 10.1039/d6ay01584k. Online ahead of print.

ABSTRACT

Manganese ferrite (MnFe₂O₄) is a promising electrode material because of its redox-active Mn and Fe centers, chemical stability, and tunable spinel structure. However, its practical use in electrochemical sensing may be limited due to its poor electrical conductivity, particle aggregation, and limited access to active sites. This review discusses recent advances in the fabrication of pristine and hybrid MnFe₂O₄-based electrochemical sensors. It is understood that synthesis methods, surface morphology, crystallinity, defects, and interfacial composition influence sensing performance. Various preparation methods such as hydrothermal, sol-gel, co-precipitation, microwave-assisted, sonochemical, electrodeposition, and thermal decomposition have been briefly discussed. The analytical sensing performance of MnFe₂O₄ incorporated with carbon materials, polymers, metal-organic framework-derived materials, chitosan, and noble-metal nanoparticles (NPs) has been discussed for the detection of heavy metals, hydrogen peroxide, pharmaceuticals, pesticides, endocrine disruptors, and biomolecules. It is believed that MnFe₂O₄-based hybrid materials may exhibit improved conductivity, active surface area, analyte adsorption, and selectivity. Therefore, MnFe₂O₄-based hybrid materials demonstrate enhanced sensing performance. Subsequently, challenges and future perspectives have been discussed.

PMID:42861664 | DOI:10.1039/d6ay01584k

Aquat Toxicol. 2026 Oct 8;301:108050. doi: 10.1016/j.aquatox.2026.108050. Online ahead of print.

ABSTRACT

Endocrine disruptors (EDs) are widely distributed in terrestrial and aquatic ecosystemsand are increasingly recognized for their potential impacts on organism health. Exposure to EDs is known to affect endocrine systems, such as the thyroid hormone system (THS), but can also manipulate the immune system (IS) of organisms. This study aimed to investigate the potential impact of the ED sodium fluoride (NaF) on the THS and pathogen resistance in rainbow trout exposed for seven months to 1.5 or 5 mg/L of fluoride (F^-). Viral resistance was assessed by subjecting the fish to an infectious challenge with the infectious hematopoietic necrosis virus (IHNV). Mortality was monitored daily for six weeks following infection. Exposure to sodium fluoride (NaF), particularly at 5 mg F^-/L, significantly increased the susceptibility of juvenile fish to viral infections, nearly doubling cumulative mortality rates. While early viral replication was not affected, NaF caused lasting changes to cellular immunity, including a reduction in circulating immune cells, disrupted leucocyte profiles and an intensified inflammatory response. The link to thyroid disruption could be drawn by showing that NaF induced temporary disruption of thyroid function (T3 and T4 concentrations) during infection and caused persistent structural changes in the thyroid gland, indicating a lasting physiological vulnerability even after hormonal levels appeared to recover.

PMID:42863161 | DOI:10.1016/j.aquatox.2026.108050

Drug Chem Toxicol. 2026 Oct 11:1-11. doi: 10.1080/01480545.2026.2697203. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a widely utilized endocrine-disrupting chemical that has been associated with metabolic dysregulation in various tissues. Nevertheless, its impact on ocular metabolism remains insufficiently understood. This study aims to investigate the metabolic effects of BPA exposure in ARPE-19 retinal pigment epithelial cells using untargeted metabolomics. ARPE-19 cells were exposed to 100 µM BPA for 24 hours, and cytotoxicity, intracellular reactive oxygen species (ROS) levels and glutathione metabolism parameters were identified. Metabolic alterations were analyzed utilizing liquid chromatography-quadrupole time-of-flight mass spectrometry (Q-TOF LC/MS). Principal component analysis (PCA), volcano plots, heatmaps, and pathway enrichment analysis were conducted to identify significantly altered metabolites and pathways. BPA exposure led to notable metabolic changes, including alterations in the tricarboxylic acid (TCA) cycle, β-oxidation, nucleoside metabolism, and amino acid metabolism. Key metabolite changes included increased levels of glutamine, pyroglutamic acid, anserine, and adenosine 2',3'-cyclic phosphate, suggesting oxidative stress and metabolic adjustment. Pathway analysis identified significant changes in arachidonic acid metabolism and pyrimidine metabolism, indicating oxidative stress and metabolic compensation due to BPA exposure. The findings underscore the metabolic risks of BPA exposure to retinal health and necessitate further validation through targeted metabolomics and in vivo studies.

PMID:42860664 | DOI:10.1080/01480545.2026.2697203

Ultrason Sonochem. 2026 Oct 1;134:108084. doi: 10.1016/j.ultsonch.2026.108084. Online ahead of print.

ABSTRACT

The continuous release of endocrine-disrupting compounds (EDCs) into Aquatic habitats have emerged as a considerable environmental issue due to their persistence, propensity for bioaccumulation, and detrimental biological consequences, even at low concentrations. Among these contaminants, diethylstilbestrol (DES), a synthetic estrogen, has attracted considerable attention because of its strong endocrine-disrupting activity and resistance to conventional wastewater treatment technologies. This study exploited multi-walled carbon nanotubes (MWCNTs) as sonocatalysts to further enhance the ultrasonic degradation of DES in educational and aquatic environments. The physiochemical properties of MWCNTs were determined using BET surface area measurements, Raman spectroscopy, and determination of the point-of-zero-charge (pHPZC). BET analyses proved the porous structure of the catalyst with pore size distribution ranging mainly from 35-45 nm. From Raman spectroscopy, well defined D, G, and 2D bands at 1338, 1584 and 2692 cm^-1 respectively were observed with ID/IG ratio 0.82 suggesting creation of active defect sites for catalyst activity. Studies were carried out with respect to varying operating parameters like liquid height, stirring speed, pH, temperature, initial DES concentration. It was found that the proposed system (ultrasonic-MWCNTs hybrid system) showed significantly higher efficiency than alone adsorption or only sonication. Optimal parameters for degradation were found to be 5 mm liquid height and 300 rpm stirring speed. From radical scavenging experiment, the reactive radical for the degradation of DES was found to be hydroxyl radicals (OH). It was also found that MWCNTs was very stable up to 5 cycles of application. The research confirmed that MWCNTs-assisted sonocatalysis is an effective and green process for removal of endocrine-disrupting pollutant from water systems.

PMID:42863377 | DOI:10.1016/j.ultsonch.2026.108084

J Ethnopharmacol. 2026 Oct 13;374(Pt 2):122512. doi: 10.1016/j.jep.2026.122512. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Due to their unique advantages of multi-target synergy and holistic regulation, traditional Chinese medicines (TCM) show promising clinical applications in enhancing male reproductive function. The 'Qianjin Fang' and 'Compendium of Materia Medica' document the use of Wuzhi Yanzong Wan, Cistanche, Cuscuta, and Epimedium for over a thousand years in the preservation of male reproductive health.

AIM OF THIS REVIEW: This article provides a systematic review of research progress on the use of active components in TCM (including flavonoids, polyphenols, terpenoids, alkaloids, and polysaccharides) and related formulas in improving male reproductive damage. These compounds improve male fertility by regulating multiple signaling pathways. Furthermore, this review outlines future research directions and potential applications in this field, aiming to lay a theoretical foundation for the clinical treatment of male reproductive health using TCM and the development of novel therapeutic interventions.

MATERIALS AND METHODS: The relevant literature on the effects of active ingredients in TCM and related formulas on improving male reproductive damage was retrieved from multiple databases, including Web of Science, ScienceDirect, PubMed, etc. RESULTS: Active components of TCM (such as icariin, hypericin, and quercetin) and their compound formulations (such as Guilu Erxian Jiao and Wuziyan Zongwan) can improve male reproductive damage by modulating core pathological cascades-including oxidative stress, inflammation, apoptosis, and endocrine disruption-and restoring the physiological microenvironment essential for normal spermatogenesis.

CONCLUSION: Extensive experiments have been performed to investigate the effects of active ingredients and herbal formulas on improving male reproductive dysfunction, revealing that TCM has the potential to combat male reproductive dysfunction through multi-level, multi-target mechanisms. However, there is a lack of reviews addressing the causes of male reproductive dysfunction and related treatment approaches. Therefore, this review aims to summarize current research progress in the use of TCM to combat male reproductive dysfunction, thereby providing a theoretical foundation for future preclinical validation and clinical application in the treatment of male reproductive dysfunction.

PMID:42863729 | DOI:10.1016/j.jep.2026.122512

Chem Biol Interact. 2026 Oct 13;440:112383. doi: 10.1016/j.cbi.2026.112383. Online ahead of print.

ABSTRACT

Halogenated disinfectants are widely used in medical, household, and industrial settings, but their inhibitory effects on 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1), a key enzyme catalyzing estrone-to-estradiol (E₂) conversion, remain unclear. We evaluated nine compounds for inhibition of human placental and rat ovarian 17β-HSD1 using enzymatic assays, kinetic analysis, BeWo cell E₂ production assays, 3D quantitative structure-activity relationship (3D-QSAR), molecular docking, molecular dynamics simulations (MDS), absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction, and network toxicology. Six compounds inhibited human 17β-HSD1, with half-maximal inhibitory concentration (IC₅₀) values of 0.78-14.90 μM; potency followed hexachlorophene > bithionol > bromochlorophene > fenticlor > dichlorophene > chlorophene. Rat 17β-HSD1 was inhibited by these six compounds and by triclosan, with IC₅₀ values of 6.13-54.77 μM. Kinetic analysis indicated mainly mixed/noncompetitive inhibition. In BeWo cells, fenticlor decreased E₂ production at ≥ 1 μM, dichlorophene at 10 and 20 μM, and bromochlorophene and hexachlorophene at 20 μM, whereas chlorophene and bithionol were inactive up to 20 μM. The 3D-QSAR model and descriptor analysis suggested associations of inhibition with hydrophobicity, aromatic features, molecular size and halogenation. Docking and 100-ns MDS supported stable binding of active compounds near the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region, particularly for hexachlorophene. Network toxicology placed HSD17B1, which encodes 17β-HSD1, within preeclampsia-related estrogen and steroidogenic pathways. These findings indicate that halogenated disinfectants may disrupt estrogen homeostasis through direct 17β-HSD1 inhibition and warrant further evaluation for reproductive and placental endocrine toxicity.

PMID:42863735 | DOI:10.1016/j.cbi.2026.112383

Ecotoxicol Environ Saf. 2026 Oct 12;325:120914. doi: 10.1016/j.ecoenv.2026.120914. Online ahead of print.

ABSTRACT

Phthalates (PAEs), as ubiquitous persistent organic pollutants and typical endocrine disruptors (EDCs), have been shown in epidemiological studies to be associated with the development of osteosarcoma (OS). However, the molecular mechanisms by which PAEs regulate the occurrence and progression of OS remain unclear. Accordingly, this study integrates network toxicology, multi-omics analysis, molecular docking, and in vitro/vivo experiments to systematically elucidate the toxicological mechanism of phthalate in promoting osteosarcoma. Specifically, this study identified COMT and SFPQ as key targets regulated by PAEs in OS, and these targets demonstrated good diagnostic performance for OS. ssGSEA confirmed that COMT and SFPQ are significantly associated with the abundance of 11 dysregulated immune cell types in OS, and single-cell sequencing revealed that COMT and SFPQ are specifically enriched in key cell populations such as osteoblasts and proliferating cells within OS tissue. Subsequently, molecular docking experiments validated that PAEs exhibit a specific binding affinity for both COMT and SFPQ. Finally, in vivo, PAE exposure induced SFPQ upregulation and COMT downregulation in normal tissues, shifting their expression pattern toward the OS-associated pattern, accompanied by enhanced cell migration and invasion in vitro. In summary, this study elucidated the molecular mechanism by which PAEs regulate OS through COMT and SFPQ as core targets using multidimensional techniques. This not only fills a gap in the microscopic mechanisms of PAE-mediated OS but also lays the foundation for developing targeted therapeutic strategies for OS associated with environmental exposure.

PMID:42863292 | DOI:10.1016/j.ecoenv.2026.120914

Maedica (Bucur). 2026 Sep;21(3):759-766. doi: 10.26574/maedica.2026.21.3.759.

ABSTRACT

Aluminium (Al) is the most abundant metal in the Earth's crust and a common environmental contaminant due to industrial processes, recycling and consumer goods. Aluminium can enter the human body via the gastrointestinal, respiratory, and skin routes, as well as through injection, although this is not essential for biological function. It can then accumulate in different organs. Its physicochemical properties enable it to displace vital metals, bind to biomolecules and interfere with cellular processes, leading to genotoxicity, oxidative stress and protein misfolding. Aluminium toxicity impacts various body systems, such as neurodegeneration, bone disorders, heart conditions, endocrine disruption and reproductive issues. Notably, Al acts as a metalloestrogen, mimicking or disrupting estrogen receptor signaling. This interference affects the hypothalamic-pituitary-gonadal axis and changes estrogen-dependent processes in both males and females. This review explores Al's systemic toxicology and its emerging function as an endocrine disruptor, highlighting its dual nature as both a sustainable industrial resource and a common biological toxin. The findings highlight important public health issues and suggest the need for further research into how Al interacts with estrogen receptors to improve prevention and treatment.

PMID:42859482 | PMC:PMC13650644 | DOI:10.26574/maedica.2026.21.3.759

J Neuroendocrinol. 2026 Oct;38(10):e70291. doi: 10.1111/jne.70291.

ABSTRACT

The circadian system enables organisms to anticipate daily environmental changes and to align physiology and behaviour with the external light-dark cycle. In mammals, this temporal organisation is coordinated by the central pacemaker in the suprachiasmatic nucleus (SCN), which synchronises peripheral clocks through humoral and neural signals throughout the body. The circadian clock and steroid hormones are linked through a reciprocal, multi-level regulatory relationship. While the SCN and peripheral clocks shape the temporal pattern of steroid secretion, steroid hormones feed back onto the SCN and peripheral clocks, thereby modifying clock gene expression, phase, amplitude, synchrony, and network coherence. This interaction is dynamic across the lifespan, as both the clock and the steroid environment change during development, reproductive life, and ageing. During prenatal and early postnatal development, maternal glucocorticoids (GCs) and other perinatal steroid signals provide time-dependent cues that may shape the maturation and long-term function of the circadian system. During reproductive life in females, ovarian steroids dynamically remodel clocks within the hypothalamic-pituitary-ovarian (HPO) axis, coordinating reproductive timing with circadian signals from the SCN. In parallel, GCs interact with the reproductive axis and may influence fertility in a time-of-day- and cycle-stage-dependent manner. Disruption of this temporal coordination, for example, by shift work, may impair reproductive and endocrine function. With advancing age, both circadian and endocrine rhythms lose robustness, leading to weakened coordination between the SCN and peripheral clocks, as well as reduced synchrony among cellular clocks within peripheral tissues. These changes contribute to disturbed sleep-wake rhythms, reproductive ageing, and altered stress responsiveness. This review discusses the interaction between steroid hormones and circadian clocks across the life span, highlighting reciprocal regulation as a key mechanism linking temporal organisation to physiology and health.

PMID:42860139 | DOI:10.1111/jne.70291

Physiol Rep. 2026 Oct;14(19):e71142. doi: 10.14814/phy2.71142.

ABSTRACT

Anorexia nervosa (AN) has been linked to both impaired and improved whole-body insulin sensitivity, but tissue-specific metabolic alterations remain unexplored. To address this gap, we studied 12 female volunteers with recently diagnosed AN and 13 healthy, lean female controls in a cross-sectional design using positron emission tomography (PET) imaging with the glucose analogue [¹⁸F]FDG tracer under hyperinsulinemic conditions. We show that tissue-specific glucose uptake during hyperinsulinemia was higher only in the duodenum of individuals with AN, but comparable in other tissues, possibly indicating altered intestinal glucose handling and nutrient sensing in reduced energy intake. In five participants with AN, glucose uptake was elevated despite reduced skeletal muscle glucose utilization. In controls, growth hormone (GH) levels correlated with skeletal muscle, liver, and brain insulin sensitivity, but these associations were absent in AN, suggesting disrupted endocrine regulation of glucose metabolism. Overall, whole-body insulin sensitivity was not altered, yet tissue-specific glucose metabolism exhibited greater variability in AN. These differences were not directly explained by disease duration or weight loss severity, suggesting contributions from individual genetic background and behavioral patterns.

PMID:42855800 | PMC:PMC13653040 | DOI:10.14814/phy2.71142

Front Endocrinol (Lausanne). 2026 Sep 25;17:1945454. doi: 10.3389/fendo.2026.1945454. eCollection 2026.

ABSTRACT

Osteoporosis is an endocrine and metabolic bone disease driven by insufficient bone formation, enhanced bone resorption, and disrupted coupling of bone remodelling. Ferroptosis, characterised by iron-dependent membrane phospholipid peroxidation and failure of anti-lipid-peroxidation defences, is emerging as a mechanistic link between oestrogen deficiency, glucolipotoxicity, glucocorticoid exposure, ageing, iron overload, and dysfunction of bone-remodelling cells. This structured narrative review summarises iron homeostasis, lipid peroxidation, the System Xc^--GSH-GPX4 axis, ferritinophagy, mitochondrial metabolism, and non-GPX4-dependent defence systems, and compares the direction and strength of ferroptotic effects in osteoblasts, osteocytes, osteoclasts, and bone marrow mesenchymal stem cells. Current evidence indicates that ferroptosis in osteoblasts and bone marrow mesenchymal stem cells impairs osteogenic differentiation, matrix formation, and mineralisation; ferroptosis in osteocytes may further disrupt RANKL-related remodelling communication; whereas ferroptosis in osteoclasts may limit bone degradation under high-resorption conditions. This review further integrates the Nrf2, NOX4, Wnt/β-catenin, DNMT/GPX4, HIF-1α/NCOA4, FtMt/PINK1/Parkin, and metabolic regulatory pathways, compares dominant cellular targets across osteoporosis subtypes, and evaluates iron chelation, inhibition of lipid peroxidation, metabolic regulation, extracellular vesicles, epigenetic restoration, and selective induction of osteoclast ferroptosis. Overall, the therapeutic objective should not be uniform inhibition or induction of ferroptosis, but selective intervention according to cell identity, disease subtype, and bone-turnover status. Because the evidence remains predominantly preclinical, translation will require cell-specific models, standardised criteria for defining ferroptosis, and bone-targeted delivery.

PMID:42857004 | PMC:PMC13650743 | DOI:10.3389/fendo.2026.1945454

Front Endocrinol (Lausanne). 2026 Sep 25;17:1935289. doi: 10.3389/fendo.2026.1935289. eCollection 2026.

ABSTRACT

Sarcopenia is characterized by a progressive loss of muscle strength and physical performance that frequently exceeds the decline predicted by muscle mass alone. This discrepancy indicates that functional deterioration is shaped not only by the force-generating capacity of skeletal muscle, but also by the tissues responsible for transmitting and integrating that force. In this Review, we examine sarcopenia through the biology of the muscle-tendon unit, encompassing skeletal muscle, tendon, and their specialized interface. We discuss how systemic aging processes, including metabolic dysfunction, inflammaging, and vascular insufficiency, produce tissue-specific and potentially asynchronous effects on muscle contractile capacity, tendon matrix remodeling, and myotendinous junction (MTJ) integrity. Much of the evidence for tendon and MTJ remodeling derives from physiological aging and experimental models, whereas their characteristic phenotypes in clinically defined sarcopenia remain insufficiently characterized. Since muscle, the MTJ, and tendon form a serial force-transmission pathway, differential remodeling across these components may create a mismatch between force-generating and force-transmitting capacities. We further evaluate the strength of evidence for inter-tissue communication, distinguishing experimentally supported muscle-to-tendon regulation from emerging tendon-to-muscle effects demonstrated primarily in co-culture, conditioned-medium, and engineered-interface systems. Particular emphasis is placed on the myotendinous junction as a structurally specialized interface where mechanical forces, extracellular matrix organization, and local signaling converge. Age-related disruption of this interface may reduce force-transfer efficiency and magnify the functional consequences of muscle weakness. Finally, we consider how the muscle-tendon unit framework may refine exercise prescription, functional phenotyping, and the evaluation of future tissue-specific interventions while remaining complementary to established diagnostic criteria and current exercise-based management. Together, these observations identify impaired coordination across the muscle-tendon unit as a potentially important contributor to loss of strength and physical performance in sarcopenia.

PMID:42857388 | PMC:PMC13650533 | DOI:10.3389/fendo.2026.1935289

Tissue Cell. 2026 Oct 6;104(Pt 3):104023. doi: 10.1016/j.tice.2026.104023. Online ahead of print.

ABSTRACT

BACKGROUND: Bisphenol A (BPA) is an endocrine-active environmental chemical that can impair testicular function through oxidative stress and disrupted steroidogenesis. Spirulina platensis (SP) has antioxidant and cytoprotective properties that may counteract BPA-induced injury. This study evaluated nanoformulated SP (NSP) against BPA-induced testicular toxicity, focusing on reproductive, structural, and molecular outcomes.

MATERIALS/METHODS: Forty adult male rats were randomly allocated into five groups (n = 8/group) and orally treated for 8 weeks: control, NSP (100 mg/kg), BPA (150 mg/kg), or BPA combined with NSP (50 or 100 mg/kg). Serum reproductive hormones, testicular oxidative stress markers, sperm quality, histopathological and morphometric analyses, immunohistochemical assessment of caspase-3 and PCNA, and selected genes related to steroidogenesis, antioxidant defense, and BDNF were assessed.

RESULTS AND DISCUSSION: BPA exposure caused marked reproductive dysfunction, characterized by reduced reproductive hormones and sperm quality, increased MDA, and decreased SOD and GPx activities. These changes were accompanied by downregulation of steroidogenic (LHR, StAR, 3β-HSD) and antioxidant (Nrf2, HO-1) genes, along with BDNF expression. Histopathological findings further revealed marked structural damage, elevated caspase-3, and reduced PCNA expression. Co-treatment with NSP, particularly at 100 mg/kg, significantly attenuated these alterations by improving hormonal levels, sperm quality, antioxidant status, and testicular architecture, while reducing lipid peroxidation and apoptosis and increasing the expression of steroidogenic and antioxidant genes, as well as BDNF expression.

CONCLUSION: Overall, NSP, particularly at the higher dose, effectively attenuated BPA-induced testicular toxicity in male rats. These findings highlight NSP as a promising natural nano-formulation for mitigating BPA-associated reproductive toxicity.

PMID:42858660 | DOI:10.1016/j.tice.2026.104023

J Hazard Mater. 2026 Oct 6;517:143833. doi: 10.1016/j.jhazmat.2026.143833. Online ahead of print.

ABSTRACT

Triclosan (TCS) is a hydrophobic and endocrine-disrupting contaminant that poses significant ecological risks. Suspended particulate matter (SPM) is ubiquitous in natural waters and can simultaneously influence both photolysis and adsorption of TCS. However, the mechanistic understanding of this dual modulation remains limited. In this study, we systematically investigated the phototransformation of TCS in SiO₂-water heterogeneous systems. Results demonstrated that SiO₂ particles generated reactive oxygen species (ROS) under irradiation, leading to accelerated photodegradation kinetics and an enhanced contribution of indirect photolysis. Adsorbed TCS exhibited slower degradation kinetics and markedly reduced pH sensitivity relative to dissolved TCS, suggesting that the adsorbed species existed in a form distinct from the ionized aqueous species. Dissolved organic matter (DOM) influenced TCS photolysis via light shielding, ROS quenching, and enhanced adsorption onto SiO₂; however, the effect of DOM was attenuated in the heterogeneous system, likely due to the increased dominance of ROS-mediated indirect photolysis, which diminished the relative importance of DOM's light-shielding effect. Notably, the solid-phase yield of 2,8-dichlorodibenzo-p-dioxin (2,8-DCDD) was lower than its aqueous-phase yield, confirming the modulating effect of SiO₂ on dioxin formation. Collectively, these findings suggested that SPM and its adsorptive interactions critically regulate TCS persistence, byproduct production, and phase-dependent transport.

PMID:42858663 | DOI:10.1016/j.jhazmat.2026.143833

Environ Sci Pollut Res Int. 2026 Oct 10. doi: 10.1007/s11356-026-38294-7. Online ahead of print.

ABSTRACT

Irgarol, originally aimed as antifouling biocide for marine environments, has become a contaminant of emerging concern due to its environmental persistence and widespread dissemination. The prevailing approach to assessment has centered on environmental prevalence and immediate toxicological repercussions, with insufficient attention paid to the dynamic mechanisms that dictate biological effects across ecological and human domains. We introduce a novel Exposure-Transformation-Response (ETR) framework, which advances the concept that Irgarol toxicity is a function of environmental persistence, biotic and abiotic transformation pathways, ecosystem transfer dynamics, and organism-specific biological responses, in addition to environmental concentrations. Through a synthesis of evidence spanning environmental chemistry, ecotoxicology, endocrine disruption research, and exposure science, we delineate the capacity of transformation products to manifest independent toxicological characteristics and illustrate how chronic, low-dose exposures can induce novel biological effects at various trophic levels. Our analysis extends to the potential for ecological disruptions to propagate through aquatic food webs, thereby contributing to previously unacknowledged human exposure pathways. The ETR framework augments existing fate-and-effects paradigms by moving towards systems toxicology, thereby providing mechanistic foundation for predictive risk assessment, pioneering sustainable antifouling solutions, and enabling next-generation regulatory strategies that address chemical persistence, transformation, and biological vulnerability within integrated environmental systems.

PMID:42859357 | DOI:10.1007/s11356-026-38294-7

Environ Res. 2026 Oct 9;309(Pt 2):125879. doi: 10.1016/j.envres.2026.125879. Online ahead of print.

ABSTRACT

Microplastics (MPs), defined as particles with a diameter <5 mm, are increasingly recognized as important global environmental stressors due to their ubiquity and harmful effects on organisms. Although most studies have investigated the direct biological effects of MPs, their role in the spread of pathogens and antibiotic resistance remains less explored. Thanks to their hydrophobic surfaces, MPs act as substrates for microbial colonization, giving rise to the plastisphere-a microenvironment that hosts opportunistic and clinically relevant bacteria, including Escherichia coli, Vibrio spp., and Aeromonas spp., some of which are multidrug-resistant. The plastisphere has emerged as a hotspot for antibiotic resistance genes (ARGs), promoting horizontal gene transfer (HGT) and contributing to the environmental spread of resistance. Human exposure to MPs is widespread, as MPs have been detected in water, food, and air. Once ingested or inhaled, they can accumulate in tissues, cross biological barriers, and cause gastrointestinal irritation, dysbiosis of the microbiota, endocrine disruptions, oxidative stress, and immunotoxicity. MPs carrying biofilms containing resistant bacteria and ARGs represent a direct route of exposure for the introduction of resistance factors into the human body, increasing the risk of untreatable infections. Despite growing evidence, significant knowledge gaps remain regarding the role of MPs in the spread of antimicrobial resistance (AMR) and associated health risks. To date, no legislation specifically considers MPs as vectors of pathogens and ARGs. This review aims to clarify the concept of the plastisphere, its implications for AMR, and the urgent need for interdisciplinary approaches to address this emerging global threat.

PMID:42854809 | DOI:10.1016/j.envres.2026.125879

Environ Toxicol. 2026 Oct 8. doi: 10.1002/tox.70201. Online ahead of print.

ABSTRACT

This study investigates the chronic effects of chlordecone (CLD) and propylparaben (PP), two pro-estrogenic endocrine disruptors, on Hydra vulgaris Pallas, 1766 using a multiscale approach over a 14-day exposure period. Environmentally relevant concentrations of CLD (0.5, 5, 20 μg L^-1) and PP (0.01, 0.05, 0.40 μg L^-1) were tested individually and in mixtures. CLD and PP single exposures reduced the asexual reproductive rate (RHR) by 20% at intermediate CLD and high PP concentrations, whereas mixtures caused stronger declines up to 60.0% at high concentration. Severe morphological damage occurred only under high-dose mixtures. We analyzed the expression of 17 genes covering detoxification, oxidative stress, endocrine function, regeneration, neurotransmission, proteolysis, and epigenetic regulation. Except for G6pd and Thypedin, single exposures to CLD and PP either increased or decreased gene expression. Only a limited subset of genes (Cyp17-like and Cyp1a-like under CLD; Cyp17-like, G6pd, and Thypedin under PP) displayed dose-related tendencies, while most other genes showed non-monotonic or irregular responses typical of endocrine disruptors. Mixture effects included antagonism, potentiation, and coalition, with non-monotonic responses such as Cyp17-like induction showing a 2-fold increase at low concentration and reversal or neutralization of oxidative-stress markers. Mixtures also increased ubiquitin in damaged hydras exposed to high-dose mixtures and reduced global DNA methylation (up to -43%). Together, these results highlight that mixture effects diverge markedly from single-compound responses, show no additive effects, reinforce the importance of assessing endocrine disruptors in combination, and confirm the relevance of H. vulgaris as a sensitive model at environmental concentrations.

PMID:42850693 | DOI:10.1002/tox.70201

Mar Pollut Bull. 2026 Oct 9;233(Pt 3):120448. doi: 10.1016/j.marpolbul.2026.120448. Online ahead of print.

ABSTRACT

Laizhou Bay is an important spawning and nursery ground for fishery species in the Bohai Sea, yet the spatial patterns of emerging endocrine disrupting chemicals (EDCs) in its surface seawater and their connection to industrial activities in the surrounding watersheds remain unclear. In the present study, 4 phenolic compounds, 7 phthalate esters (PAEs), and 11 perfluoroalkyl substances (PFAS) were concurrently quantified at 25 stations across the bay. Total phenolic, PAE, and PFAS concentrations ranged from 0.05 to 0.92 μg/L, below detection to 1.12 μg/L, and below detection to 0.21 μg/L, respectively. Phenolic compounds and PAEs were concentrated near the Yellow River estuary, whereas PFAS peaked near the Xiaoqing River estuary and adjacent smaller rivers. Bisphenol A exhibited its highest concentrations near the Mihe, Bailang, and Yuhe River estuaries, likely reflecting urban and industrial inputs from the Weifang area and rapid removal from the dissolved phase in the sediment-laden Yellow River plume. This spatial divergence reflects the differing industrial geography of the contributing watersheds. Phenols and PAEs originate from diffuse sources along the densely populated Yellow River corridor, while PFAS are linked to fluorochemical manufacturing facilities concentrated in the Xiaoqing basin. The low PFAS concentrations in the Yellow River estuary further suggest that contaminant loads are driven by specific industrial sectors rather than by river discharge volume. These findings indicate that effective pollution control in fishery ecosystems requires strategies matched to the source characteristics of different pollutants, rather than uniform regulatory measures.

PMID:42854656 | DOI:10.1016/j.marpolbul.2026.120448

Environ Res. 2026 Oct 9;309(Pt 2):125879. doi: 10.1016/j.envres.2026.125879. Online ahead of print.

ABSTRACT

Microplastics (MPs), defined as particles with a diameter <5 mm, are increasingly recognized as important global environmental stressors due to their ubiquity and harmful effects on organisms. Although most studies have investigated the direct biological effects of MPs, their role in the spread of pathogens and antibiotic resistance remains less explored. Thanks to their hydrophobic surfaces, MPs act as substrates for microbial colonization, giving rise to the plastisphere-a microenvironment that hosts opportunistic and clinically relevant bacteria, including Escherichia coli, Vibrio spp., and Aeromonas spp., some of which are multidrug-resistant. The plastisphere has emerged as a hotspot for antibiotic resistance genes (ARGs), promoting horizontal gene transfer (HGT) and contributing to the environmental spread of resistance. Human exposure to MPs is widespread, as MPs have been detected in water, food, and air. Once ingested or inhaled, they can accumulate in tissues, cross biological barriers, and cause gastrointestinal irritation, dysbiosis of the microbiota, endocrine disruptions, oxidative stress, and immunotoxicity. MPs carrying biofilms containing resistant bacteria and ARGs represent a direct route of exposure for the introduction of resistance factors into the human body, increasing the risk of untreatable infections. Despite growing evidence, significant knowledge gaps remain regarding the role of MPs in the spread of antimicrobial resistance (AMR) and associated health risks. To date, no legislation specifically considers MPs as vectors of pathogens and ARGs. This review aims to clarify the concept of the plastisphere, its implications for AMR, and the urgent need for interdisciplinary approaches to address this emerging global threat.

PMID:42854809 | DOI:10.1016/j.envres.2026.125879

Chem Biol Interact. 2026 Oct 9;440:112376. doi: 10.1016/j.cbi.2026.112376. Online ahead of print.

ABSTRACT

BACKGROUND: Spondyloarthritis (SpA), including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), involves complex interactions between genetic susceptibility and environmental factors. Bisphenol A (BPA), an endocrine-disrupting chemical with immunomodulatory properties, may influence immune regulation, but its relationship with SpA remains unclear.

METHODS: BPA-associated targets (CTD and ChEMBL) and AS- and PsA-related genes (GeneCards and OMIM) were collected. Shared targets were identified through network analysis and hub screening. GEO datasets were used to evaluate shared targets' expression patterns. Molecular docking and 100-ns molecular dynamics simulations assessed BPA interactions with core shared targets. NHANES data were analyzed to evaluate population-level associations between urinary BPA and PsA, as AS assessment was limited by insufficient BPA measurements.

RESULTS: BPA shared 1076 targets with AS and 598 targets with PsA. Five cytokines (TNF-α, IL-10, IL-6, IL-1β, and IFN-γ) were identified as shared targets. TNF-α was decreased in both AS and PsA datasets, whereas IL-10 was increased in AS and showed an upward trend in PsA. The cytokine signature showed preliminary classification potential in transcriptomic datasets of AS (AUC = 0.831) and PsA (AUC = 0.899), although validation in larger cohorts is required. Molecular simulations supported stable BPA interactions, particularly with TNF-α and IL-10. NHANES analysis showed higher urinary BPA concentrations in PsA participants than controls (1.468 vs. 1.054 ng/mL, P = 0.338).

CONCLUSION: These findings suggest that BPA exposure may be associated with SpA-related immune dysregulation through cytokine networks, particularly the TNF-α/IL-10 axis. However, given the non-significant population-level association, further experimental and longitudinal studies are warranted.

PMID:42854943 | DOI:10.1016/j.cbi.2026.112376

EFSA J. 2026 Oct 8;24(10):e10325. doi: 10.2903/j.efsa.2026.10325. eCollection 2026 Oct.

ABSTRACT

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State, France, for the pesticide active substance cyazofamid are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory information with regard to the endocrine disruption potential of cyazofamid for humans and wild mammals for the EATS modalities and for non-target organisms other than mammals. The conclusions were reached on the basis of the evaluation of the representative uses of cyazofamid as a fungicide on potatoes, tomatoes and cucurbits. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and/or literature in the dossier peer reviewed, are presented. Assessments not finalised, together with the missing information identified as being required by the regulatory framework, are listed.

PMID:42852149 | PMC:PMC13647298 | DOI:10.2903/j.efsa.2026.10325

PLoS Pathog. 2026 Oct 9;22(10):e1014667. doi: 10.1371/journal.ppat.1014667. Online ahead of print.

ABSTRACT

Human African Trypanosomiasis (HAT) or sleeping sickness is a systemic parasitic infection caused by the protozoan parasite Trypanosoma brucei. HAT is associated with substantial immunological, metabolic, and neurological pathology. Although reproductive dysfunction has previously been recognised in both human and experimental T. brucei infection, whether parasites can directly infiltrate the female reproductive tract (FRT), and how infection may reshape the FRT immune landscape remains poorly understood. Using a murine model of T. brucei infection we reveal that parasites are localised in the uterine lining (endometrium) during both acute and chronic infection stages in mice. Chronic T. brucei infection was associated with progressive fat wasting, disruption of the reproductive (oestrous) cycle, uterine and ovarian atrophy, and extensive transcriptional dysregulation across the hypothalamic-pituitary-gonadal (HPG) axis. Acute and chronic infection induced remodelling of the uterine immune landscape, characterised by T cell infiltration, pro-inflammatory myeloid activation, alongside broader type 1 inflammatory changes across reproductive tissues and HPG components. Ovarian pathology was accompanied by follicular degeneration, a reduction in corpora lutea and alterations to steroidogenic pathways. Hormonal rescue with the selective oestrogen receptor modulator, tamoxifen, restored uterine morphology and prevented oestrous cycle arrest, but did not reverse the infection-induced uterine immune remodelling, indicating that endocrine dysfunction and infection-driven inflammation are distinct processes. Taken together, these findings identify the FRT as a major target of T. brucei infection and demonstrate how chronic parasitic infection can disrupt reproductive physiology through a combination of immune, endocrine, and metabolic pathways. They also highlight the need to specifically assess the FRT in other models of systemic inflammation.

PMID:42853904 | DOI:10.1371/journal.ppat.1014667

Mol Biol Rep. 2026 Oct 9;53(1):1691. doi: 10.1007/s11033-026-12842-3.

ABSTRACT

BACKGROUND: Mentha pulegium L. essential oil (MPEO), or pennyroyal oil, is widely used in traditional medicine, yet its safety remains debated because of pulegone, a constituent linked to hepatotoxicity and reproductive toxicity. This study evaluated MPEO's hepato-reproductive toxicity using an integrated in-silico and in vivo approach.

METHODS: Phytochemical composition was determined by GC-MS, while network pharmacology and molecular docking were used to identify likely targets and pathways. Reproductive and developmental toxicity were then assessed in Wistar rats (OECD Guideline 421) given 100, 200, or 400 mg/kg MPEO during premating, mating, gestation, and lactation, evaluating reproductive performance, developmental outcomes, biochemical markers, oxidative stress, hormone levels, and histopathology.

RESULTS: GC-MS confirmed pulegone (42.72%) as the major constituent, and network pharmacology revealed 116 shared targets, with CYP19A1, ESR2, and HSD11B1 emerging as key hub genes in steroid hormone biosynthesis and estrogen signaling. Molecular docking showed favorable pulegone binding affinities for these targets (-5.9, -6.0, and - 6.6 kcal/mol, respectively). In vivo, MPEO exposure produced dose-dependent impairments in fertility, implantation, litter size, pup survival, and offspring growth, alongside elevated liver injury markers, oxidative stress, hormonal disruption, and histopathological damage in liver, testes, and ovaries.

CONCLUSION: Pulegone-rich MPEO induces hepato-reproductive toxicity through endocrine disruption, oxidative tissue injury, and downregulation of steroid hormone biosynthesis signaling pathway. The novelty of this study lies in establishing the first multi-scale mechanistic link between computational targets (CYP19A1, ESR2, HSD11B1) and in vivo toxicity outcomes, offering insight for toxicology risk assessment and regulatory limits on pulegone-containing phytoactives.

PMID:42853327 | DOI:10.1007/s11033-026-12842-3

EMBO Mol Med. 2026 Oct 9. doi: 10.1038/s44321-026-00525-2. Online ahead of print.

ABSTRACT

Adamantinomatous craniopharyngiomas (aCPs) are complex intracranial neoplasms that arise in the sellar and suprasellar region of the brain, affecting the endocrine and nervous systems, causing severe sequelae. Although most of aCPs are driven by somatic mutations in β-catenin (CTNNB1), some cases remain genetically unresolved. Here, we show that disruption of the Wnt-antagonist and tumour suppressor adenomatous polyposis coli (Apc) leads to pituitary tumours that present all classic molecular and histopathological hallmarks of aCPs. Mechanistically, we show that a hypomorphic allele of Apc leads to tumour development and that bi-allelic loss of Apc in the Sox2+ve pituitary stem cells can initiate aCP formation. Apc-driven tumour-initiating cells show a distinct transcriptional signature of p21-mediated senescence-associated secretory phenotype (SASP) with methylomic analyses revealing shared epigenetic alteration of SASP-like inflammatory programme across aCP subtypes. Our data demonstrate a causal role of disruption of Apc in driving aCPs, reinforcing the importance of genetic testing for mutations in APC in patients with aCP. Furthermore, our work highlights the need to screen patients with familial adenomatous polyposis (FAP) or the spectrum of APC-pathogenic syndromes for aCP development early in life.

PMID:42855520 | DOI:10.1038/s44321-026-00525-2

PeerJ. 2026 Oct 5;14:e21773. doi: 10.7717/peerj.21773. eCollection 2026.

ABSTRACT

Cybutryne (irgarol) is a triazine biocide formerly used in antifouling paints worldwide and still detected in freshwater ecosystems in Europe, Asia, and North America despite its ban in antifouling paints in Europe in January 2017 and in the USA in April 2021. While primary producers are considered the most sensitive targets due to cybutryne's mode of action as a photosystem II inhibitor, data on freshwater invertebrates-particularly from standardized chronic tests-remain scarce. In this study, we investigated acute and chronic effects of cybutryne on three freshwater invertebrates representing major taxonomic phyla: the midge Chironomus riparius (Arthropoda), the blackworm Lumbriculus variegatus (Annelida), and the freshwater mudsnail Potamopyrgus antipodarum (Mollusca). Acute toxicity tests showed low sensitivity, with immobilization observed only in C. riparius larvae at mg/L concentrations (48 h 50% effect concentration (EC₅₀) = 2.96 mg/L), while no acute effects occurred in L. variegatus or P. antipodarum up to five mg/L. In chronic sediment-water tests, C. riparius exhibited no significant effects on survival, emergence, development time, sex ratio, or reproduction at concentrations up to five µg/L. In L. variegatus, reproduction was the most sensitive endpoint, with a 28-day 10% effect concentration (EC₁₀) of 0.268 µg/L (95% confidence interval: 0-462 µg/L) and a lowest observed effect concentration (LOEC) of 0.8 µg/L. In contrast, chronic reproduction tests with P. antipodarum revealed pronounced and consistent increases in embryo numbers at all tested cybutryne concentrations (0.05-5 µg/L), resulting in inverted U-shaped concentration-response relationships that precluded derivation of a no observed effect concentration (NOEC) or EC₁₀ values using conventional monotonic concentration-response models. Exploratory evaluation of quadratic hormesis-type models confirmed the non-monotonic inverted U-shaped concentration-response relationship. However, robust benchmark-concentration estimates could not be derived. The reproductive responses resembled those induced by estrogenic positive controls (17α-ethinylestradiol and bisphenol A) but the present results do not provide direct mechanistic evidence for endocrine disruption. Our results demonstrate that acute cybutryne exposure did not result in negative effects for the test organisms in the applied concentration range of up to five mg/L, except for C. riparius, while chronic reproductive endpoints-particularly in mollusks-appeared to be highly sensitive and suggest the possibility of endocrine-related or other non-specific reproductive modulation mechanisms that require further mechanistic investigation. These findings highlight the importance of including sensitive invertebrate reproduction tests in environmental risk assessment of antifouling biocides.

PMID:42852046 | PMC:PMC13648218 | DOI:10.7717/peerj.21773

Mar Pollut Bull. 2026 Oct 9;233(Pt 3):120448. doi: 10.1016/j.marpolbul.2026.120448. Online ahead of print.

ABSTRACT

Laizhou Bay is an important spawning and nursery ground for fishery species in the Bohai Sea, yet the spatial patterns of emerging endocrine disrupting chemicals (EDCs) in its surface seawater and their connection to industrial activities in the surrounding watersheds remain unclear. In the present study, 4 phenolic compounds, 7 phthalate esters (PAEs), and 11 perfluoroalkyl substances (PFAS) were concurrently quantified at 25 stations across the bay. Total phenolic, PAE, and PFAS concentrations ranged from 0.05 to 0.92 μg/L, below detection to 1.12 μg/L, and below detection to 0.21 μg/L, respectively. Phenolic compounds and PAEs were concentrated near the Yellow River estuary, whereas PFAS peaked near the Xiaoqing River estuary and adjacent smaller rivers. Bisphenol A exhibited its highest concentrations near the Mihe, Bailang, and Yuhe River estuaries, likely reflecting urban and industrial inputs from the Weifang area and rapid removal from the dissolved phase in the sediment-laden Yellow River plume. This spatial divergence reflects the differing industrial geography of the contributing watersheds. Phenols and PAEs originate from diffuse sources along the densely populated Yellow River corridor, while PFAS are linked to fluorochemical manufacturing facilities concentrated in the Xiaoqing basin. The low PFAS concentrations in the Yellow River estuary further suggest that contaminant loads are driven by specific industrial sectors rather than by river discharge volume. These findings indicate that effective pollution control in fishery ecosystems requires strategies matched to the source characteristics of different pollutants, rather than uniform regulatory measures.

PMID:42854656 | DOI:10.1016/j.marpolbul.2026.120448

Arch Med Res. 2026 Oct 8;58(1):103524. doi: 10.1016/j.arcmed.2026.103524. Online ahead of print.

ABSTRACT

BACKGROUND: Maternal diabetes and exposure to a high‑fat diet (HFD) disrupt pancreatic development and glucose homeostasis, potentially inducing transgenerational metabolic changes.

OBJECTIVE: Investigate how maternal diabetes and HFD exposure impact the endocrine pancreas across generations. Elucidate their effects on oxidative stress, cellular senescence, proliferation, cell death, and islet architecture in a transgenerational manner.

METHODS: Female Sprague‑Dawley rats (F1) were allocated into four groups (n=10/group): i) Offspring from non‑diabetic dams fed a standard diet (OC/SD); ii) Offspring from non‑diabetic dams fed an HFD (OC/HFD); iii) Offspring from diabetic dams fed a standard diet (OD/SD); and iv) Offspring from diabetic dams fed an HFD (OD/HFD). At postnatal day 90 (adulthood), the F1 females were mated and euthanized on gestational day 21 for pancreas harvesting for immunochemistry and morphological analysis. Their offspring (F2) were also obtained for pancreatic evaluation. Statistical significance was set at p <0.05.

RESULTS: OD/HFD rats showed a 14.5% reduction in glucagon‑positive cells compared to the other groups. OC/HFD, OD/SD, and OD/HFD rats exhibited increased proportions of somatostatin‑positive (43.8%), cleaved caspase‑3‑positive (30.2%), and 4‑HNE‑positive (>100%) cells, along with reduced Ki‑67‑positive cells, relative to OC/SD rats. Newborns from OC/HFD dams had higher proportions of insulin‑, glucagon‑, and somatostatin‑positive cells than those from other dams.

CONCLUSION: Our findings suggest that maternal diabetes, regardless of HFD exposure, predisposes female offspring to future pancreatic dysfunction and an increased risk of metabolic disease, highlighting sex‑specific vulnerability of females to transgenerational programming.

PMID:42854641 | DOI:10.1016/j.arcmed.2026.103524

bioRxiv [Preprint]. 2026 Aug 11:2026.08.05.743028. doi: 10.64898/2026.08.05.743028.

ABSTRACT

Chemical exposures during pregnancy are linked to an increased risk of pregnancy complications that contribute significantly to maternal and infant morbidity and mortality and can lead to long term health consequences for both the mother and the offspring. The placenta, a central regulator of pregnancy health, is a direct target of environmental toxicants. Epidermal growth factor receptor (EGFR), highly expressed in the placenta, regulates proliferation, migration, invasion, fusion, and cellular bioenergetics. To identify compounds of environmental concern with potential for EGFR-disrupting activity, we optimized a high-throughput virtual screening protocol for the identification of EGFR inhibitors and achieved enrichment factors of EF₁% = 10.09, EF₅% = 3.86, and EF₁₀% = 3.0 in a benchmarking dataset. We applied this protocol to screen the Collaborative Estrogen Receptor Activity Prediction Project database, finding that top-scoring compounds were enriched for aromatic and fused-ring chemical classes, including dyes. Kinase activity assays revealed that two out of thirteen selected compounds, Vat Red 32 and Reactive Red 136, inhibited EGFR kinase activity with micromolar IC₅₀ values. Additionally, pose refinement with molecular dynamics simulations characterized the binding interactions of Reactive Red 136 within the EGFR kinase domain, and functional assays in HTR-8/SVneo placental trophoblast cells showed that Reactive Red 136, but not Vat Red 32, partially attenuated EGF-mediated cell migration despite both compounds inhibiting EGFR kinase activity. Together, this study has generated an enriched dataset of candidate environmental EGFR modulators, with experimental validation confirming enrichment for EGFR-disrupting activity among the selected compounds. These results provide a valuable resource for toxicological studies.

PMID:42845303 | PMC:PMC13640559 | DOI:10.64898/2026.08.05.743028

bioRxiv [Preprint]. 2026 Aug 11:2026.08.10.743339. doi: 10.64898/2026.08.10.743339.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy originating from the adrenal cortex with limited effective treatment options. The underlying pathophysiology of ACC is uniquely characterized by abnormal steroid production and increased metabolic activity, highlighting the critical role of mitochondria in adrenal steroid hormone biosynthesis and tumor metabolism. In this study, we investigated the therapeutic potential of TR-107, a novel and highly selective small-molecule agonist targeting the mitochondrial protease ClpP. Pharmacologic hyperactivation of ClpP disrupts mitochondrial proteostasis and bioenergetics and has shown promising antitumor activity in various preclinical models. Our results demonstrated that TR-107 induces potent dose-dependent cytotoxic effects at nanomolar concentrations in ACC cell lines NCI-H295R and mACC3 as well as short-term ACC patient-derived organoid (PDO) models, markedly reducing cell viability and confluency in vitro . Metabolic analyses revealed that TR-107 significantly impaired oxygen consumption, indicating a disruption of oxidative phosphorylation and substantial attenuation of basal cellular respiration. Mechanistic studies showed dose-dependent increases in reactive oxygen species (ROS) levels and upregulation of proteins involved in mediating the ferroptotic rheostat. Pharmacokinetic assessment uncovered that TR-107 was not a substrate of the ABCB1 (MDR1/P-glycoprotein) efflux transporter, suggesting potential to overcome common multidrug resistance mechanisms. Given the importance of IGF-2 signaling in ACC, we further explored the combinatorial effects of TR-107 with IGF-1 receptor (IGF-1R) inhibitors and discovered that co-treatment produced synergistic reductions in cell viability across NCI-H295R, mACC3, and ACC PDOs. Collectively, these findings support the potential of mitochondrial ClpP hyperactivation as a promising therapeutic strategy for ACC and demonstrate that TR-107 exhibits significant antitumor activity as a monotherapy or in combination with IGF-1R inhibitors. These findings provide a strong rationale for advancing ClpP agonists into clinical development for the management of ACC.

PMID:42845394 | PMC:PMC13640636 | DOI:10.64898/2026.08.10.743339

Mol Cancer Ther. 2026 Oct 8. doi: 10.1158/1535-7163.MCT-26-0239. Online ahead of print.

ABSTRACT

Hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer that progresses on CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) faces a major therapeutic challenge, and chemotherapy is frequently used despite its modest clinical benefit. Paclitaxel is commonly used in this setting; however, intrinsic and acquired resistance substantially limit the depth and durability of response. Polo-like kinase 1 (PLK1) is a key mitotic regulator implicated in resistance to taxanes and ET/CDK4/6i. We evaluated whether PLK1 inhibition with onvansertib enhances paclitaxel activity in HR+ breast cancer models with intrinsic or acquired ET/CDK4/6i resistance, testing across six cell lines and eight patient-derived xenograft models, including paclitaxel-resistant tumors. The combination synergistically inhibited cell viability in vitro and improved antitumor efficacy in xenograft models. Notably, the combination induced tumor regression across all paclitaxel-resistant models, with complete responses in more than half of treated animals in three of five models, and deep, durable regressions in paclitaxel-sensitive models, markedly outperforming either agent alone. Mechanistically, the combination exacerbated mitotic stress, disrupted spindle architecture, suppressed proliferative and cell-cycle-associated transcriptional programs, and promoted proteasome-dependent c-MYC degradation, resulting in enhanced apoptotic cell death in vitro and in vivo. Importantly, genetic modulation of c-MYC expression altered the apoptotic response, establishing c-MYC downregulation as a key mediator of the observed antitumor efficacy. Collectively, these findings support PLK1 inhibition as a mechanistically rational strategy to potentiate taxane efficacy and overcome resistance in advanced HR+/HER2-negative breast cancer.

PMID:42847288 | DOI:10.1158/1535-7163.MCT-26-0239

Reprod Toxicol. 2026 Oct 8;146:109375. doi: 10.1016/j.reprotox.2026.109375. Online ahead of print.

ABSTRACT

Microplastics and nanoplastics (MNPs) are pervasive environmental contaminants linked to reproductive and developmental health. Plastic particles or polymeric residues have been detected in human blood, placenta, meconium, breast milk, fetal appendages, and umbilical venous blood, indicating maternal-fetal interface exposure during pregnancy. Fetal growth restriction (FGR) is a placental syndrome in which the fetus fails to achieve its growth potential, and impaired placental vascular, transport, endocrine, immune, and metabolic functions contribute to its pathogenesis. Experiments with polystyrene or polyethylene particles report fetal growth impairment, altered placental hemodynamics, defective trophoblast differentiation, mitochondrial and endoplasmic-reticulum stress, disrupted cholesterol and nicotinamide metabolism, lipid remodeling, and ferroptosis-associated injury. This targeted narrative review synthesizes human biomonitoring, animal, ex vivo, and omics evidence, with emphasis on placental fatty-acid uptake and oxidation, cholesterol trafficking, glycerophospholipid remodeling, nicotinamide/NAD⁺ homeostasis, oxidative lipid injury, and ferroptosis. Current evidence supports a plausible framework in which MNP exposure contributes to placental lipid metabolic dysregulation and thereby increases vulnerability to fetal growth impairment. However, human causal evidence remains insufficient, and the term MNPs should not obscure important differences between microplastics and nanoplastics in particle size, tissue penetration, detectability, and biological activity. Major uncertainties include contamination control, polymer and particle heterogeneity, environmental dose translation, gestational timing, co-exposure to additives and pollutants, and inconsistent FGR phenotyping. Prospective pregnancy cohorts and human-relevant placental models integrating validated particle detection, fetal growth trajectories, spatial and single-cell omics, metabolic-flux analysis, and rescue experiments are required to determine whether placental lipid dysregulation is a causal mediator of MNP-associated fetal growth restriction.

PMID:42849766 | DOI:10.1016/j.reprotox.2026.109375

Environ Pollut. 2026 Oct 8:129282. doi: 10.1016/j.envpol.2026.129282. Online ahead of print.

ABSTRACT

While the endocrine-disrupting potential of heavy metals and per- and polyfluoroalkyl substances (PFAS) is well-documented in laboratory settings, evidence from wild populations remains sparse. This study investigated the impact of a suite of legacy and emerging contaminants, including five heavy metals, four mineral elements, and eleven PFAS, on the thyroid hormone (TH) levels of three wild fish species inhabiting the coastal waters of Qingdao, China. The results showed that three PFAS, including perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), were significantly positively correlated with free (FT3), total triiodothyronine (TT3), or the free triiodothyronine/thyroxine ratio (FT3:FT4), indicating a stimulatory or compensatory TH response. In contrast, heavy metals exhibited divergent effects: chromium (Cr) showed a significant negative correlation with FT3 and TT3, whereas total mercury (THg) was positively associated with TT3. Furthermore, increasing phosphorus (P) and calcium (Ca) were linked to a decrease in the FT3:FT4 ratio. Partial least square analysis identified a statistically supported association between TT3 and a co-varying exposure pattern, with PFDA, PFUdA, 6:2 Cl-PFESA, MeHg, Cr, and Zn having the highest VIP values within the identified pattern. Notably, several contaminant-TH interactions were species-specific, suggesting varying sensitivity to chemical stress among marine teleosts. Our findings underscore the potent thyroid-disrupting potential of PFAS and heavy metals in natural ecosystems, and highlight the complex, multi-contaminant exposure profiles encountered by wild fish populations.

PMID:42849695 | DOI:10.1016/j.envpol.2026.129282

Reprod Toxicol. 2026 Oct 8;146:109375. doi: 10.1016/j.reprotox.2026.109375. Online ahead of print.

ABSTRACT

Microplastics and nanoplastics (MNPs) are pervasive environmental contaminants linked to reproductive and developmental health. Plastic particles or polymeric residues have been detected in human blood, placenta, meconium, breast milk, fetal appendages, and umbilical venous blood, indicating maternal-fetal interface exposure during pregnancy. Fetal growth restriction (FGR) is a placental syndrome in which the fetus fails to achieve its growth potential, and impaired placental vascular, transport, endocrine, immune, and metabolic functions contribute to its pathogenesis. Experiments with polystyrene or polyethylene particles report fetal growth impairment, altered placental hemodynamics, defective trophoblast differentiation, mitochondrial and endoplasmic-reticulum stress, disrupted cholesterol and nicotinamide metabolism, lipid remodeling, and ferroptosis-associated injury. This targeted narrative review synthesizes human biomonitoring, animal, ex vivo, and omics evidence, with emphasis on placental fatty-acid uptake and oxidation, cholesterol trafficking, glycerophospholipid remodeling, nicotinamide/NAD⁺ homeostasis, oxidative lipid injury, and ferroptosis. Current evidence supports a plausible framework in which MNP exposure contributes to placental lipid metabolic dysregulation and thereby increases vulnerability to fetal growth impairment. However, human causal evidence remains insufficient, and the term MNPs should not obscure important differences between microplastics and nanoplastics in particle size, tissue penetration, detectability, and biological activity. Major uncertainties include contamination control, polymer and particle heterogeneity, environmental dose translation, gestational timing, co-exposure to additives and pollutants, and inconsistent FGR phenotyping. Prospective pregnancy cohorts and human-relevant placental models integrating validated particle detection, fetal growth trajectories, spatial and single-cell omics, metabolic-flux analysis, and rescue experiments are required to determine whether placental lipid dysregulation is a causal mediator of MNP-associated fetal growth restriction.

PMID:42849766 | DOI:10.1016/j.reprotox.2026.109375

J Control Release. 2026 Oct 8;399(Pt A):115449. doi: 10.1016/j.jconrel.2026.115449. Online ahead of print.

ABSTRACT

Spermatogenic disorders are a major cause of male infertility, with oxidative stress-driven Leydig cell dysfunction serving as a key pathological contributor. However, effective antioxidant therapy remains limited by insufficient accumulation in injured testes and by the formulation complexity associated with conventional carrier-based delivery systems. Here, we investigated the pathological microenvironment of di(2-ethylhexyl) phthalate (DEHP)-injured testes and found increased inducible nitric oxide synthase (iNOS) expression together with upregulation of the cationic amino acid transporter 2 (CAT2) in the testicular interstitium, indicating altered arginine metabolism and transport. Based on this pathological feature, we constructed carrier-free maltol-arginine nanoparticles (MAS) through Mannich reaction-mediated covalent conjugation and non-covalent self-assembly. In this system, the arginine moiety functions as a CAT2-recognizable structural cue for lesion-oriented delivery, whereas maltol provides antioxidant activity for redox regulation. MAS preferentially accumulated in injured testes and showed enhanced uptake by Leydig cells in vitro. Mechanistically, MAS promoted Nrf2 nuclear translocation, improved redox homeostasis, and attenuated NF-κB/NLRP3/GSDMD-mediated pyroptotic signaling. In the murine injury model, MAS ameliorated testicular microenvironmental disruption, improved Leydig cell-associated endocrine function, and enhanced sperm quality. Overall, this study presents a functionally engineered, carrier-free biomaterial strategy that redirects pathology-related arginine transport remodeling into a metabolic delivery advantage, providing a viable strategy for targeted intervention in spermatogenic disorders and restoration of testicular homeostasis.

PMID:42849851 | DOI:10.1016/j.jconrel.2026.115449

Toxicol Sci. 2026 Oct 7:kfag135. doi: 10.1093/toxsci/kfag135. Online ahead of print.

ABSTRACT

Humans are exposed to complex mixtures of endocrine-disrupting chemicals (EDCs) in the real world. Most prior studies, however, focus on individual EDCs. Here, we investigated the ovarian impact of organic pollutant mixtures extracted from the Raritan River, a heavily industrialized watershed in central New Jersey, using a three-dimensional (3D) in vitro ovarian follicle culture system. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) identified organic pollutant mixtures dominated by alkylphenols, pharmaceuticals, per- and polyfluoroalkyl substances (PFAS), and phthalates, together with previous reports demonstrating that the Raritan River also contains hydrophobic persistent organic pollutants (POPs), including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and dioxins. In vitro exposure to the Raritan River-derived EDC mixture did not affect follicle growth and ovulation but dose-dependently increased preovulatory testosterone (T) secretion while suppressing postovulatory progesterone (P4) production. Transcriptomic analysis, Gene set enrichment analysis (GSEA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and in situ RNA hybridization revealed widespread reprogramming of follicular somatic cell gene expression, including altered steroidogenic pathways and activation of aryl hydrocarbon receptor (AhR) signaling. An established AhR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), reproduced the phenotype of EDC mixture-induced hyperandrogenism, which was reversed by a selective AhR inhibitor. Together, this study demonstrates that real-world EDC mixtures, particularly AhR-activating chemicals, disrupt ovarian steroidogenesis and induce hyperandrogenism, highlighting EDC mixtures as an underrecognized mechanism potentially linking aquatic pollution to impaired women's reproductive health.

PMID:42844579 | DOI:10.1093/toxsci/kfag135

Reproduction. 2026 Oct 8:xaag127. doi: 10.1093/reprod/xaag127. Online ahead of print.

ABSTRACT

Circadian rhythms are fundamental regulators of physiology and play a critical role in reproductive success. During pregnancy, precise temporal coordination of endocrine, metabolic, and immune processes is required to support maternal adaptation, placental function, and foetal development. Disruption of circadian rhythms through environmental factors such as light at night, shift work, or sleep disorders has emerged as a significant risk factor for adverse pregnancy outcomes, including preterm birth, gestational diabetes, and preeclampsia. In this review, we synthesize current evidence linking circadian and sleep disruption to pregnancy complications, with a particular focus on the temporal regulation of key hormones, including progesterone, oestrogen, cortisol, oxytocin, and melatonin. We discuss how altered rhythmicity of hormone production and tissue responsiveness may impair target tissue function, maternal cardiovascular adaptation, and the development of gestational diabetes. We highlight emerging mechanistic insights into molecular clock regulation across reproductive tissues and its interaction with environmental cues. Finally, we outline opportunities for clinical translation, including chronobiology-informed diagnostics and chronotherapeutic strategies, to improve pregnancy management and reduce the burden of adverse outcomes.

PMID:42850565 | DOI:10.1093/reprod/xaag127

Environ Pollut. 2026 Oct 8:129282. doi: 10.1016/j.envpol.2026.129282. Online ahead of print.

ABSTRACT

While the endocrine-disrupting potential of heavy metals and per- and polyfluoroalkyl substances (PFAS) is well-documented in laboratory settings, evidence from wild populations remains sparse. This study investigated the impact of a suite of legacy and emerging contaminants, including five heavy metals, four mineral elements, and eleven PFAS, on the thyroid hormone (TH) levels of three wild fish species inhabiting the coastal waters of Qingdao, China. The results showed that three PFAS, including perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), were significantly positively correlated with free (FT3), total triiodothyronine (TT3), or the free triiodothyronine/thyroxine ratio (FT3:FT4), indicating a stimulatory or compensatory TH response. In contrast, heavy metals exhibited divergent effects: chromium (Cr) showed a significant negative correlation with FT3 and TT3, whereas total mercury (THg) was positively associated with TT3. Furthermore, increasing phosphorus (P) and calcium (Ca) were linked to a decrease in the FT3:FT4 ratio. Partial least square analysis identified a statistically supported association between TT3 and a co-varying exposure pattern, with PFDA, PFUdA, 6:2 Cl-PFESA, MeHg, Cr, and Zn having the highest VIP values within the identified pattern. Notably, several contaminant-TH interactions were species-specific, suggesting varying sensitivity to chemical stress among marine teleosts. Our findings underscore the potent thyroid-disrupting potential of PFAS and heavy metals in natural ecosystems, and highlight the complex, multi-contaminant exposure profiles encountered by wild fish populations.

PMID:42849695 | DOI:10.1016/j.envpol.2026.129282

Toxicol Sci. 2026 Oct 7:kfag135. doi: 10.1093/toxsci/kfag135. Online ahead of print.

ABSTRACT

Humans are exposed to complex mixtures of endocrine-disrupting chemicals (EDCs) in the real world. Most prior studies, however, focus on individual EDCs. Here, we investigated the ovarian impact of organic pollutant mixtures extracted from the Raritan River, a heavily industrialized watershed in central New Jersey, using a three-dimensional (3D) in vitro ovarian follicle culture system. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) identified organic pollutant mixtures dominated by alkylphenols, pharmaceuticals, per- and polyfluoroalkyl substances (PFAS), and phthalates, together with previous reports demonstrating that the Raritan River also contains hydrophobic persistent organic pollutants (POPs), including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and dioxins. In vitro exposure to the Raritan River-derived EDC mixture did not affect follicle growth and ovulation but dose-dependently increased preovulatory testosterone (T) secretion while suppressing postovulatory progesterone (P4) production. Transcriptomic analysis, Gene set enrichment analysis (GSEA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and in situ RNA hybridization revealed widespread reprogramming of follicular somatic cell gene expression, including altered steroidogenic pathways and activation of aryl hydrocarbon receptor (AhR) signaling. An established AhR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), reproduced the phenotype of EDC mixture-induced hyperandrogenism, which was reversed by a selective AhR inhibitor. Together, this study demonstrates that real-world EDC mixtures, particularly AhR-activating chemicals, disrupt ovarian steroidogenesis and induce hyperandrogenism, highlighting EDC mixtures as an underrecognized mechanism potentially linking aquatic pollution to impaired women's reproductive health.

PMID:42844579 | DOI:10.1093/toxsci/kfag135

Front Endocrinol (Lausanne). 2026 Sep 22;17:1934568. doi: 10.3389/fendo.2026.1934568. eCollection 2026.

ABSTRACT

BACKGROUND: Despite successful CSF diversion for pediatric obstructive hydrocephalus, up to 40% of children in Sub-Saharan Africa develop persistent neurodevelopmental delay, growth arrest, and executive dysfunction. Models based on axonal injury or ischemia alone do not fully explain this burden.

HYPOTHESIS: We propose the Hypothalamic Compression-Endocrine-Glymphatic Dysfunction Theory. Third ventricular expansion compresses and shears periventricular hypothalamic neurons, particularly TRH-secreting cells of the paraventricular nucleus. This disrupts pulsatile TRH release and impairs TSH glycosylation. The resulting biologically inactive TSH is detected on routine immunoassays but fails to stimulate the thyroid, causing cryptic central hypothyroidism that standard screening misses.

MECHANISM: Thyroid hormone deficiency downregulates and mislocalizes Aquaporin-4 (AQP4) at the neurovascular unit, causing glymphatic stasis and impaired waste clearance. This creates a cycle: ventricular distension suppresses hypothalamic output, inducing central hypothyroidism that compromises microstructural clearance and intracranial compliance, driving neurocognitive deficits despite pressure normalization.

LMIC RELEVANCE: In low-resource settings, CT surrogates can stratify risk. Third ventricular width >8 mm plus Evans' Index >0.30 identifies patients needing targeted free T4 testing. Automated deep-learning CSF segmentation offers scalable diagnosis.

CONCLUSION: Treating hydrocephalus-induced central hypothyroidism with levothyroxine alongside surgical decompression may improve outcomes. Multicenter trials in Nigeria are needed to validate these CT-endocrine indices.

PMID:42840695 | PMC:PMC13639570 | DOI:10.3389/fendo.2026.1934568

Front Public Health. 2026 Sep 22;14:1860620. doi: 10.3389/fpubh.2026.1860620. eCollection 2026.

ABSTRACT

BACKGROUND: Resin-based dental composites are the most widely placed direct restorative materials globally. Yet, their organic matrix and complex filler system render them a potential source of biologically active compounds. Residual monomers, including Bisphenol A-glycidyl dimethacrylate (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), and urethane dimethacrylate (UDMA), are released into the oral environment through incomplete polymerization, material degradation, and wear, and may subsequently reach systemic circulation. Composite matrix breakdown additionally generates micro- and nanoplastic particles (MNPs), representing a distinct emerging exposure pathway. This review synthesizes clinical and translational evidence on the oral-systemic toxicological implications of resin-based composite materials, with emphasis on biomonitoring data, mechanistic pathways, and relevant risk signals.

METHODS: A structured search was conducted across PubMed/MEDLINE, Embase, Scopus, and Web of Science for studies published between January 1990 and September 2025. Eligible studies reported biomonitoring outcomes (saliva, blood, urine, breast milk, cord blood, or placenta), toxicokinetic profiles, or systemic and generalized hypersensitivity reactions attributable to resin-based restorative materials. Studies on dental amalgam and non-dental polymer exposures were excluded. Data were synthesized narratively in accordance with SANRA principles.

RESULTS: Released monomers exert concentration-dependent cytotoxic, genotoxic, and immunomodulatory effects, primarily through glutathione depletion, reactive oxygen species generation, and apoptosis induction. Local adverse effects, including gingival inflammation, pulp cytotoxicity, and allergic contact stomatitis, are well-documented in vitro and in clinical case reports. Systemically, BPA and its derivatives have been detected in saliva, urine, blood, breast milk, cord blood, and placenta following dental procedures, raising concerns regarding endocrine-disrupting potential, particularly in children and pregnant women. Dental personnel constitute a distinct occupational risk group through dermal monomer exposure. Composite resins also release MNPs through wear and degradation, with preliminary data suggesting inflammatory and genotoxic potential, though clinical significance remains to be established.

CONCLUSION: Resin composites pose a measurable, if generally low-level, toxicological risk through monomer elution and, increasingly, MNP release. Adequate operative technique substantially reduces patient exposure. Vulnerable populations, including children, pregnant women, and dental personnel, warrant particular attention. Standardized biomonitoring protocols, updated regulatory thresholds, and dedicated in vivo studies are needed to characterize the long-term oral-systemic health implications of these ubiquitous materials.

PMID:42840843 | PMC:PMC13639877 | DOI:10.3389/fpubh.2026.1860620

Reproduction. 2026 Oct 7:xaag126. doi: 10.1093/reprod/xaag126. Online ahead of print.

ABSTRACT

The mammalian ovary is a structurally and functionally dynamic tissue that undergoes cyclical changes involved in folliculogenesis, ovulation, and luteal function. Each process depends on the coordination of complex cell biology such as steroidogenesis, inflammation and vascular remodeling that are regulated at transcriptional and post-translational levels. CCAAT/enhancer-binding proteins (C/EBPs) are a family of transcription factors emerging as key regulators of these processes, in particular C/EBPα and C/EBPβ. The upstream regulation and downstream biological effects of C/EBPα and C/EBPβ are context-dependent and vary depending on the state of ovarian follicles and corpus luteum. These factors integrate local ovarian and endocrine signals to orchestrate ovarian function, and genetic disruption of their expression leads to obstructed primordial follicle formation, impaired ovulation, defective luteinization, and reduced fertility. This narrative review synthesizes current knowledge on the expression, regulation, and function of C/EBP transcription factors, particularly C/EBPα and C/EBPβ, in ovarian biology. It highlights the current knowledge gap and future directions in further defining the role of C/EBP transcription factors in ovarian function and dysfunction.

PMID:42841721 | DOI:10.1093/reprod/xaag126

Endocrine. 2026 Oct 7;91(1):335. doi: 10.1007/s12020-026-04809-y.

ABSTRACT

PURPOSE: Leptin is an adipokine that regulates energy balance and is commonly linked to obesity. It exhibits a circadian rhythm that can be disrupted by variations in eating times and sleep disorders. This brief review explored how leptin can modulate appetite and tissue repair; and assessed whether dysregulated serum levels may activate pro-inflammatory pathways contributing to inflammatory dermatoses, particularly in the context of obesity.

METHODS: Current evidence on the interconnection between leptin rhythmicity, obesity, sleep disruption, meal timing, oxidative stress, and inflammatory dermatoses was reviewed and synthesized, with an emphasis on studies relevant to the proposed circadian, metabolic and cutaneous axis.

RESULTS: Available evidence indicated that irregular or late meal timing can alter leptin rhythmicity, while sleep disruption is associated with changes in leptin secretion and inflammatory mediators. In obesity, persistent hyperleptinemia may coexist with central leptin resistance and preserved peripheral pro-inflammatory signaling. Experimental and clinical findings support associations among leptin dysregulation, oxidative stress, reduced antioxidant capacity, and inflammatory pathways relevant to dermatoses related to obesity, particularly psoriasis. However, direct evidence establishing a causal relationship between circadian leptin dysregulation and skin inflammation remains limited.

CONCLUSIONS: Circadian leptin misalignment may represent a plausible upstream pathway linking altered meal timing, sleep disruption, leptin resistance, oxidative stress, and immune activation to obesity-associated inflammatory dermatoses. Chronobiological interventions, particularly time-restricted feeding combined with adequate sleep, warrant further investigation for their potential to improve leptin regulation and attenuate skin inflammation. Much of the current evidence remains associative, and further mechanistic and interventional studies are needed to test this hypothesis.

PMID:42842099 | PMC:PMC13645989 | DOI:10.1007/s12020-026-04809-y

Annu Rev Anim Biosci. 2026 Oct 7. doi: 10.1146/annurev-animal-031325-104351. Online ahead of print.

ABSTRACT

Pesticides are widely used in agricultural systems globally, and wild vertebrates are commonly exposed to them in both terrestrial and aquatic ecosystems. This review synthesizes current knowledge on pesticide classes, environmental fate, exposure pathways, and their effects across major nonhuman vertebrate taxa. We highlight both direct toxic effects, including neurotoxicity, endocrine disruption, and oxidative stress, and indirect exposure mediated through food web alterations. Aquatic vertebrates, particularly fish and amphibians, emerge as highly vulnerable due to continuous exposure of sensitive developmental stages. Despite growing evidence, significant knowledge gaps persist, notably for reptiles and in understanding chronic and mixture exposure. Current regulatory frameworks remain limited by their focus on model species and acute toxicity endpoints. We argue that pesticides play a substantial, though context dependent, role in vertebrate declines and emphasize the need for integrative, ecologically realistic approaches to improve risk assessment and biodiversity conservation.

PMID:42842840 | DOI:10.1146/annurev-animal-031325-104351

Pediatr Res. 2026 Oct 7. doi: 10.1038/s41390-026-05366-w. Online ahead of print.

ABSTRACT

Perfluorinated alkylate substances (PFASs) have been in use for about 75 years. Because of their persistence, concentrations in the environment have increased, and absorbed PFAS will remain in the human body, some compounds for many years. The fetus and the newborn infant are particularly vulnerable to PFAS toxicity due to the intense development of organs and body functions. In addition, PFASs pass the placenta so that a pregnant woman shares her accumulated PFAS burden with the progeny. In addition, PFASs are excreted in the milk, so that the resulting serum-PFAS concentration in the infant may greatly exceed that of the mother. Multi-organ effects have been reported, some related to endocrine disruption. Immunotoxicity can occur at very low exposure levels, with elevated risks of infectious disease and possibly also cancer development. Unfortunately, little research was carried out during the first 50 years of industrial use, and some study reports were hidden. Independent research has been carried out only recently. Due to incomplete evidence, governmental regulations have been delayed and remain insufficient, in part because of objections from industrial interests. IMPACT: The perfluorinated alkylate substances (PFASs) are persistent and accumulate in the environment and in the human body. The greatest risk of PFAS toxicity occurs at early age, as PFASs are transferred through the placenta and human milk. This means that early-life exposures may trigger development of diseases and other adverse outcomes that may seriously burden adult health. Research has been delayed due to secrecy. While pediatric studies in this field are underway, prudent decisions to protect public health should be made despite possible concerns regarding incomplete evidence. Practical complications, and current guidelines and interventions are by far insufficient. Current evidence on PFASs shows that these industrial chemicals are persistent and that highly elevated exposures occur already at early age. The maternal body burden of PFAS is shared with the fetus, and substantial amounts are transferred in human milk, thus impacting the unique nutritional advantage of breast-feeding. Recent evidence suggests that early PFAS exposure can affect public health, also during adult age, and that some adverse effects may be transferred to the next generation.

PMID:42844334 | DOI:10.1038/s41390-026-05366-w

Pediatr Res. 2026 Oct 7. doi: 10.1038/s41390-026-05366-w. Online ahead of print.

ABSTRACT

Perfluorinated alkylate substances (PFASs) have been in use for about 75 years. Because of their persistence, concentrations in the environment have increased, and absorbed PFAS will remain in the human body, some compounds for many years. The fetus and the newborn infant are particularly vulnerable to PFAS toxicity due to the intense development of organs and body functions. In addition, PFASs pass the placenta so that a pregnant woman shares her accumulated PFAS burden with the progeny. In addition, PFASs are excreted in the milk, so that the resulting serum-PFAS concentration in the infant may greatly exceed that of the mother. Multi-organ effects have been reported, some related to endocrine disruption. Immunotoxicity can occur at very low exposure levels, with elevated risks of infectious disease and possibly also cancer development. Unfortunately, little research was carried out during the first 50 years of industrial use, and some study reports were hidden. Independent research has been carried out only recently. Due to incomplete evidence, governmental regulations have been delayed and remain insufficient, in part because of objections from industrial interests. IMPACT: The perfluorinated alkylate substances (PFASs) are persistent and accumulate in the environment and in the human body. The greatest risk of PFAS toxicity occurs at early age, as PFASs are transferred through the placenta and human milk. This means that early-life exposures may trigger development of diseases and other adverse outcomes that may seriously burden adult health. Research has been delayed due to secrecy. While pediatric studies in this field are underway, prudent decisions to protect public health should be made despite possible concerns regarding incomplete evidence. Practical complications, and current guidelines and interventions are by far insufficient. Current evidence on PFASs shows that these industrial chemicals are persistent and that highly elevated exposures occur already at early age. The maternal body burden of PFAS is shared with the fetus, and substantial amounts are transferred in human milk, thus impacting the unique nutritional advantage of breast-feeding. Recent evidence suggests that early PFAS exposure can affect public health, also during adult age, and that some adverse effects may be transferred to the next generation.

PMID:42844334 | DOI:10.1038/s41390-026-05366-w

Front Endocrinol (Lausanne). 2026 Sep 22;17:1987603. doi: 10.3389/fendo.2026.1987603. eCollection 2026.

ABSTRACT

Diabetic cardiomyopathy (DCM) is characterized by mitochondrial metabolic inflexibility, redox imbalance and defective organelle quality control, yet the endocrine program coordinating these abnormalities remains incompletely defined. Thyroid hormone (TH) is a major regulator of cardiac energy metabolism and mitochondrial adaptation. In experimental diabetes, myocardial triiodothyronine (T3) can decline despite preserved circulating thyroid hormone concentrations, accompanied by type 3 iodothyronine deiodinase (DIO3) induction and altered TH transport. We propose that this local defect disrupts thyroid hormone-mitochondrial coupling and may thereby constrain adaptation of substrate oxidation, oxidative phosphorylation, redox defense and organelle turnover. Preclinical diabetic-heart studies demonstrate local TH dysregulation and show that appropriately dosed T3 treatment can reverse selected structural and functional abnormalities. Complementary cardiac studies identify mitochondrial biogenesis, reactive oxygen species control, mitophagy and calcium handling as plausible downstream effectors. Together, these findings support impaired local TH signaling as an underrecognized candidate upstream mechanism linking the diabetic endocrine environment to mitochondrial maladaptation. A tissue-specific therapeutic-window model may reconcile the adverse consequences of both deficient and excessive TH signaling while providing a framework for biomarker development, mechanistic testing and precision intervention in DCM.

PMID:42840385 | PMC:PMC13639578 | DOI:10.3389/fendo.2026.1987603

Front Public Health. 2026 Sep 22;14:1860620. doi: 10.3389/fpubh.2026.1860620. eCollection 2026.

ABSTRACT

BACKGROUND: Resin-based dental composites are the most widely placed direct restorative materials globally. Yet, their organic matrix and complex filler system render them a potential source of biologically active compounds. Residual monomers, including Bisphenol A-glycidyl dimethacrylate (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), and urethane dimethacrylate (UDMA), are released into the oral environment through incomplete polymerization, material degradation, and wear, and may subsequently reach systemic circulation. Composite matrix breakdown additionally generates micro- and nanoplastic particles (MNPs), representing a distinct emerging exposure pathway. This review synthesizes clinical and translational evidence on the oral-systemic toxicological implications of resin-based composite materials, with emphasis on biomonitoring data, mechanistic pathways, and relevant risk signals.

METHODS: A structured search was conducted across PubMed/MEDLINE, Embase, Scopus, and Web of Science for studies published between January 1990 and September 2025. Eligible studies reported biomonitoring outcomes (saliva, blood, urine, breast milk, cord blood, or placenta), toxicokinetic profiles, or systemic and generalized hypersensitivity reactions attributable to resin-based restorative materials. Studies on dental amalgam and non-dental polymer exposures were excluded. Data were synthesized narratively in accordance with SANRA principles.

RESULTS: Released monomers exert concentration-dependent cytotoxic, genotoxic, and immunomodulatory effects, primarily through glutathione depletion, reactive oxygen species generation, and apoptosis induction. Local adverse effects, including gingival inflammation, pulp cytotoxicity, and allergic contact stomatitis, are well-documented in vitro and in clinical case reports. Systemically, BPA and its derivatives have been detected in saliva, urine, blood, breast milk, cord blood, and placenta following dental procedures, raising concerns regarding endocrine-disrupting potential, particularly in children and pregnant women. Dental personnel constitute a distinct occupational risk group through dermal monomer exposure. Composite resins also release MNPs through wear and degradation, with preliminary data suggesting inflammatory and genotoxic potential, though clinical significance remains to be established.

CONCLUSION: Resin composites pose a measurable, if generally low-level, toxicological risk through monomer elution and, increasingly, MNP release. Adequate operative technique substantially reduces patient exposure. Vulnerable populations, including children, pregnant women, and dental personnel, warrant particular attention. Standardized biomonitoring protocols, updated regulatory thresholds, and dedicated in vivo studies are needed to characterize the long-term oral-systemic health implications of these ubiquitous materials.

PMID:42840843 | PMC:PMC13639877 | DOI:10.3389/fpubh.2026.1860620

Anthropol Med. 2026 Oct 6:1-17. doi: 10.1080/13648470.2026.2687249. Online ahead of print.

ABSTRACT

Chlordecone, a highly persistent organochlorine insecticide, was widely applied to banana plantations in Martinique and Guadeloupe from 1972 until being banned in 1993. Decades later, its residues still permeate soil, waterways, food systems, and human bodies in the two islands. Classified as both a carcinogenic and an endocrine disruptor, the chemical compound has generated widespread protests, epidemiological debates, and political critique. Drawing on six months of non-consecutive ethnographic fieldwork conducted in Martinique between 2017 and 2022, this article examines how people interpret and navigate the chemical's enduring effects. We develop the concept of 'articulations of poisoning' to describe the ways in which Chlordecone is rendered meaningful, not simply as a biomedical or ecological risk, but as a lived, historically sedimented, and politically contested experience. These articulations unfold along three interconnected dimensions (i.e. historicity, relationality, and contextuality) that shape how poisoning is perceived, embodied, and contested in everyday life. Through the voices of activists, farmers, medical professionals, institutional actors, and community members, we explore how poisoning becomes entangled with colonial legacies, political debates, and the everyday struggle for environmental justice in the French Antilles.

PMID:42839532 | DOI:10.1080/13648470.2026.2687249

Front Physiol. 2026 Sep 21;17:1953796. doi: 10.3389/fphys.2026.1953796. eCollection 2026.

ABSTRACT

Military aviation exposes aircrew to interacting physiological and operational stressors that are often studied in isolation. These stressors are experienced by the whole body: pulmonary, cardiovascular, musculoskeletal, endocrine, and immune responses may influence cerebral perfusion, blood-brain barrier function, fatigue, and recovery. Evidence from aviation cohorts, altitude-chamber studies, and adjacent fields suggests that some exposures may converge on neurovascular, blood-brain barrier, perivascular, and inflammatory pathways before overt neurological disease is apparent. This narrative review evaluates the glymphatic system as one potentially important component of that broader injury-and-recovery network, rather than as a sole or established primary mechanism. We synthesize evidence concerning hypobaria and decompression, intermittent hypoxia and hyperoxia, high +Gz, sleep and circadian disruption, operational wakefulness-promoting agents, noise, cosmic ionizing radiation, and context-dependent chemical exposures. Direct human evidence of glymphatic dysfunction in tactical aviators remains absent, and findings from lower-intensity hypobaric exposure and retrospective clinical cohorts are mixed or null. Exposure profiles also differ substantially among fighter, cargo/tanker, helicopter, and remotely piloted aircraft communities. We therefore propose an exposure-resolved research agenda combining longitudinal neuroimaging, circulating biomarkers, electroencephalography, cognitive testing, sleep phenotyping, dosimetry, and controlled single- and combined-stressor experiments. This calibrated glymphatic-neurovascular framework generates testable hypotheses about cumulative brain stress and recovery while preserving alternative explanations involving direct tissue injury, cerebral perfusion, endothelial dysfunction, oxidative stress, systemic and central inflammation, and autonomic regulation.

PMID:42835435 | PMC:PMC13635881 | DOI:10.3389/fphys.2026.1953796

NPJ Womens Health. 2026;4(1):31. doi: 10.1038/s44294-026-00162-7. Epub 2026 Aug 28.

ABSTRACT

Paraben esters are endocrine disruptors linked to breast cancer, yet their role in other estrogen-mediated cancers remains limited. Preclinical evidence suggests that parabens accumulate in tissues and may promote carcinogenesis, while clinical data indicate widespread exposure. Our re-analysis of cervicovaginal metabolomes revealed elevated paraben metabolites in endometrial and cervical cancer patients compared with controls. Overall, longitudinal studies considering intrinsic and environmental factors are needed in assessing paraben-related cancer risk.

PMID:42836018 | PMC:PMC13637036 | DOI:10.1038/s44294-026-00162-7

Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2026 Oct 6:1-14. doi: 10.1080/19440049.2026.2701456. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) and its substitutes Bisphenol S (BPS) and Bisphenol F (BPF) have been identified as endocrine-disrupting chemicals that affects reproductive functions. In Korea, BPA use has been restricted, resulting in increased utilisation of BPS and BPF as alternatives. However, risk assessment and exposure management of these alternatives remain limited. Therefore, we conducted a risk assessment of BPA, BPS, and BPF prioritising human-use products while considering additional environmental exposure pathways. Product concentration data, usage amounts, and frequency factors were studied for products considered in the National Institute of Food and Drug Safety Evaluation between 2023 and 2024. Based on the data, the estimated daily exposure levels of the general Korean population indicated that food is the primary source of bisphenol exposure. The age-specific exposure levels corresponded to 0.02-0.12% of the health-based guidance value. Risk characterisation based on the hazard index for BPA and the margin of exposure approach for BPS and BPF revealed that current regulatory measures have managed BPA, BPS, and BPF exposures effectively. Reassessment should be considered if new evidence of unrecognised toxicities becomes available. These findings highlight the need for continuous monitoring of alternative bisphenols to ensure public health protection.

PMID:42836715 | DOI:10.1080/19440049.2026.2701456

J Environ Manage. 2026 Oct 1;418:131057. doi: 10.1016/j.jenvman.2026.131057. Epub 2026 Oct 6.

ABSTRACT

Pharmaceuticals, microplastics, per- and polyfluoroalkyl substances (PFAS) and endocrine-disrupting compounds are increasingly discharged in treated wastewater, are not effectively removed by conventional secondary treatment, and have important implications for the environment and human health. Advanced tertiary treatment is needed for safe reuse of urban non-potable water, but the choice among competing technologies is a complex decision involving technical, economic, environmental and regulatory considerations, as well as uncertainty and reluctance in expert evaluations. To address this issue, this research uses a decision support system based on Probabilistic T-Spherical Hesitant Fuzzy Numbers (Pt-SHFNs) that represents probabilistic uncertainty, ambiguity and expert hesitance consistently. A hybrid method is used to find criteria weights. The hybrid method combines the Level-Based Weight Assessment (LBWA) technique and changes of empirical data. This allows the subjective preferences of experts and objective evidence to be simultaneously considered. Then the alternatives are ranked using Comprehensive Distance Based Ranking (COBRA) technique. The results show that in the practical case of seven tertiary treatment systems, the effectiveness of removal of emerging pollutants (0.2319) and capital expenditures (0.1713) are the most influential factors. The most efficient systems are hybrid membrane-advanced oxidation process systems (0.0338) followed by ozonation-biofiltration (0.0203) and nanofiltration membranes (-0.0022). The stability analysis and comparison studies with other MCDM techniques increase the dependability and consistency of the obtained rankings. The proposed technique provides an explicit and uncertainty-aware basis for ranking tertiary alternatives to treatment and could assist wastewater utilities and regulators in integrating technical decisions with sustainability and water reuse objectives.

PMID:42837953 | DOI:10.1016/j.jenvman.2026.131057

Talanta. 2026 Oct 1;313(Pt A):130702. doi: 10.1016/j.talanta.2026.130702. Online ahead of print.

ABSTRACT

Herein, a mesoporous carbon material was prepared via pyrolysis of a melamine-resorcinol formaldehyde copolymer synthesized in the presence of mesoporous hydroxyapatite (HA) nanostructures, as a hard template. The porous HA nanostructures were prepared through a novel strategy that involved synthesizing calcium carbonate nanostructures on CTAB micellar aggregations as a soft template, followed by carbonate-phosphate replacement under hydrothermal conditions. This approach yielded microspheres composed of rod-like nanostructures featuring ordered approximately 1 nm nanochannels, exhibiting a BET surface area of 51.17 m² g^-1 and a BJH-derived characteristic pore diameter of 18.46 nm. The XRD analysis of the carbon product indicated the presence of a graphitic carbon structure, consistent with the Raman spectroscopy results. Additionally, the presence of oxygen and nitrogen heteroatoms and their related functional groups in the carbon framework was confirmed by elemental analysis and FT-IR spectroscopy. Based on BET analysis, the carbon product exhibited a high specific surface area of 882.78 m² g^-1, a large pore volume of 3.944 cm³ g^-1, and a characteristic pore diameter of 32.58 nm obtained from BJH analysis. BET analysis highlighted the role of CTAB and carbonate in the synthesis of the HA template, enabling the achievement of high-surface-area mesoporous carbon. The combination of high porosity, graphitic domains, and oxygen- and nitrogen-containing species makes the material a promising adsorbent for the extraction of relatively polar aromatic compounds. The synthesized carbon material was employed as an effective adsorbent for the dispersive solid-phase extraction (SPE) of some parabens, preservatives with endocrine-disrupting effects, with detection using HPLC-UV. The experimental design methodology efficiently determined optimal extraction conditions while minimizing the number of experiments and analyzing parameter interactions. Under the optimized conditions, a good analytical performance for the proposed method was achieved with a linearity of 0.1-100.0 μg L^-1 (R² ≥ 0.998) and preconcentration factors ranging from 84 to 116 for the target analytes. The applicability of the proposed method was assayed in real samples with different matrices, yielding satisfactory relative recoveries (89-111%) and RSD values (n = 3) ranging from 2.4% to 7.9%.

PMID:42837780 | DOI:10.1016/j.talanta.2026.130702

J Environ Manage. 2026 Oct 1;418:131090. doi: 10.1016/j.jenvman.2026.131090. Epub 2026 Oct 6.

ABSTRACT

Water contamination by hazardous organic pollutants poses a significant threat to human health. Among these, phenolic compounds, particularly 4-nitrophenol (4-NP), are of special concern due to their high toxicity and carcinogenic, endocrine-disrupting, and genotoxic effects. This study explores the photocatalytic reduction of 4-NP using, for the first time in this reaction, BiOCl-TiO₂ composites prepared in various ratios by ball milling of home-made BiOCl nanosheets and commercial TiO₂. The selective photocatalytic reduction of 4-NP to 4-aminophenol (4-AP), a high-value chemical intermediate, was investigated in aqueous dispersion as an integrated approach that combines pollutant removal with the production of value-added compounds. The influence of the presence of triethanolamine (TEOA), sodium borohydride (NaBH₄) and 4-methoxybenzyl alcohol (4-MBA), used as sacrificial agents, in the reagent system was systematically evaluated. Formation of 4-AP occurred only in the presence of these hole scavengers, confirming their essential role in promoting the reduction pathway. It should be noted, however, that 4-MBA took part in the reaction not only as a trap for the holes, allowing the reduction of 4-NP to 4-AP by the photoproduced electrons, but also by being transformed itself by partial oxidation into the high-value compound 4-methoxybenzaldehyde (4-MBAL). In the integrated system, the optimal performance was achieved with 5%BiOCl-TiO₂ in the presence of both TEOA and 4-MBA, yielding 94% 4-NP conversion and 99% selectivity toward 4-AP after 3 h of irradiation, along with 6% 4-MBA conversion and 50% selectivity toward 4-MBAL.

PMID:42837952 | DOI:10.1016/j.jenvman.2026.131090

J Environ Manage. 2026 Oct 1;418:131057. doi: 10.1016/j.jenvman.2026.131057. Epub 2026 Oct 6.

ABSTRACT

Pharmaceuticals, microplastics, per- and polyfluoroalkyl substances (PFAS) and endocrine-disrupting compounds are increasingly discharged in treated wastewater, are not effectively removed by conventional secondary treatment, and have important implications for the environment and human health. Advanced tertiary treatment is needed for safe reuse of urban non-potable water, but the choice among competing technologies is a complex decision involving technical, economic, environmental and regulatory considerations, as well as uncertainty and reluctance in expert evaluations. To address this issue, this research uses a decision support system based on Probabilistic T-Spherical Hesitant Fuzzy Numbers (Pt-SHFNs) that represents probabilistic uncertainty, ambiguity and expert hesitance consistently. A hybrid method is used to find criteria weights. The hybrid method combines the Level-Based Weight Assessment (LBWA) technique and changes of empirical data. This allows the subjective preferences of experts and objective evidence to be simultaneously considered. Then the alternatives are ranked using Comprehensive Distance Based Ranking (COBRA) technique. The results show that in the practical case of seven tertiary treatment systems, the effectiveness of removal of emerging pollutants (0.2319) and capital expenditures (0.1713) are the most influential factors. The most efficient systems are hybrid membrane-advanced oxidation process systems (0.0338) followed by ozonation-biofiltration (0.0203) and nanofiltration membranes (-0.0022). The stability analysis and comparison studies with other MCDM techniques increase the dependability and consistency of the obtained rankings. The proposed technique provides an explicit and uncertainty-aware basis for ranking tertiary alternatives to treatment and could assist wastewater utilities and regulators in integrating technical decisions with sustainability and water reuse objectives.

PMID:42837953 | DOI:10.1016/j.jenvman.2026.131057

Food Chem Toxicol. 2026 Oct 6;219:116430. doi: 10.1016/j.fct.2026.116430. Online ahead of print.

ABSTRACT

Colon cancer is a global health threat characterized by marked heterogeneity and therapeutic resistance. Although environmental pollutants may contribute to tumor progression, the role of diethyl phthalate (DEP), a widely used plasticizer and endocrine disruptor, remains unclear. By integrating clinical cohort data, bioinformatics, and in vitro and in vivo models, we investigated the oncogenic effects and mechanisms of DEP in colon cancer. Elevated serum DEP was independently associated with shorter overall survival, and DEP exposure accelerated subcutaneous tumor growth in vivo. In vitro, DEP enhanced cell migration and epithelial-mesenchymal transition (EMT), while suppressing ferroptosis by reducing intracellular iron accumulation and lipid peroxidation. LASSO regression and tumor immune microenvironment profiling further established a DEP-related prognostic signature associated with an immune-cold phenotype, characterized by reduced CD4⁺ and CD8⁺ memory T cells and increased M2 macrophage infiltration. ALDOC was identified as a key downstream mediator of DEP-induced malignancy. DEP markedly upregulated ALDOC, whereas ALDOC knockdown reversed EMT activation, restored ferroptosis sensitivity, and inhibited cell migration. These findings demonstrate that DEP promotes colon cancer progression through the ALDOC/EMT axis and ferroptosis evasion, highlighting ALDOC as a potential therapeutic target.

PMID:42838491 | DOI:10.1016/j.fct.2026.116430

Food Chem Toxicol. 2026 Oct 6;218:116421. doi: 10.1016/j.fct.2026.116421. Online ahead of print.

ABSTRACT

Bisphenol A (BPA), an endocrine-disrupting chemical widely detected in human populations, has been implicated in metabolic disorders following early-life exposure. However, the long-term effects of developmental BPA exposure on adipose metabolism under post-weaning dietary challenge remain incompletely understood. Pregnant C57BL/6J mice received BPA in drinking water at a maternal nominal target exposure of 50 μg/kg/day from gestational day 6 to postnatal day 21. After weaning, offspring were fed a normal diet or high-fat diet and evaluated at PND22, PND36, and PND91. Body weight, adipose morphology, serum biochemical parameters, hepatic histology, metabolic gene expression, untargeted lipidomics, and targeted ceramide profiles were assessed. BPA-associated alterations were more pronounced in females. BPA exposure was associated with reduced adipose expansion under high-fat feeding, reflected by smaller adipocytes and lower fat depot-to-body weight ratios, together with stage- and depot-dependent changes in adipose metabolic gene expression. Lipidomic analyses revealed alterations in glycerophospholipid composition, while targeted profiling identified depot-specific changes in ceramide species and the 24:1 ceramide/dihydroceramide ratio. Female offspring also showed stage-dependent hepatic morphological and aminotransferase changes. Overall, developmental BPA exposure was associated with female-predominant alterations in adipose morphology, metabolic gene expression, and lipid remodeling, with responses influenced by post-weaning diet.

PMID:42838492 | DOI:10.1016/j.fct.2026.116421

EBioMedicine. 2026 Oct;132:106487. doi: 10.1016/j.ebiom.2026.106487. Epub 2026 Oct 6.

ABSTRACT

BACKGROUND: Phthalates are known male endocrine disruptors and reproductive toxicants. Despite growing evidence of female effects, mechanistic knowledge in key reproductive organs remains limited, hindering regulations. Here, we conducted an experimental study to map the impact of mono(2-ethylhexyl) phthalate (MEHP), the primary metabolite of di(2-ethylhexyl) phthalate (DEHP), on adult human ovarian tissue at single-cell resolution.

METHODS: Ovarian tissue explants from seven donors (five gender-affirming surgery, two caesarean-section) were exposed to two MEHP concentrations: an epidemiologically relevant 20.51 nM and a 1000-fold higher 20.51 μM. After six days, single-cell RNA sequencing (one donor) and immunostainings (six donors) were used to characterise gene expression changes across cell types. Primary ovarian cells derived from three gender-affirming surgery patients and stem cell-derived Schwann cells were used for validation.

FINDINGS: Explants retained all major ovarian cell types, including rare glial cells and oocytes. MEHP altered transcriptomes across all cell types, disrupting pathways related to actin cytoskeleton, cell adhesion, and oxidative phosphorylation (OXPHOS). Protein analyses confirmed altered EIF5A, MT-ND3, MT-ND4L, and VCL expression, genes linked to mitochondrial translation, OXPHOS, adhesion, and cytoskeleton. MEHP also reduced cell-cell communication, particularly glial-stromal interactions. Mitochondrial stress assay in primary cells indicated increased proton leakage, and Schwann cell responses mirrored the scRNA-seq findings.

INTERPRETATION: Ovarian toxicity studies traditionally focus on follicles, but this study reveals the susceptibility of non-follicular cells. Importantly, the sensitivity of ovarian nervous system cells to MEHP offers new mechanistic insights into reported links between phthalates, altered ovarian sensitivity index, and polyendocrine metabolic ovarian syndrome. Our findings highlight the need for a holistic assessment of ovarian toxicity that considers all ovarian cell types, not only follicles.

FUNDING: Swedish Research Council for Sustainable Development and the European Union.

PMID:42838884 | DOI:10.1016/j.ebiom.2026.106487

J Environ Manage. 2026 Oct 1;418:131057. doi: 10.1016/j.jenvman.2026.131057. Epub 2026 Oct 6.

ABSTRACT

Pharmaceuticals, microplastics, per- and polyfluoroalkyl substances (PFAS) and endocrine-disrupting compounds are increasingly discharged in treated wastewater, are not effectively removed by conventional secondary treatment, and have important implications for the environment and human health. Advanced tertiary treatment is needed for safe reuse of urban non-potable water, but the choice among competing technologies is a complex decision involving technical, economic, environmental and regulatory considerations, as well as uncertainty and reluctance in expert evaluations. To address this issue, this research uses a decision support system based on Probabilistic T-Spherical Hesitant Fuzzy Numbers (Pt-SHFNs) that represents probabilistic uncertainty, ambiguity and expert hesitance consistently. A hybrid method is used to find criteria weights. The hybrid method combines the Level-Based Weight Assessment (LBWA) technique and changes of empirical data. This allows the subjective preferences of experts and objective evidence to be simultaneously considered. Then the alternatives are ranked using Comprehensive Distance Based Ranking (COBRA) technique. The results show that in the practical case of seven tertiary treatment systems, the effectiveness of removal of emerging pollutants (0.2319) and capital expenditures (0.1713) are the most influential factors. The most efficient systems are hybrid membrane-advanced oxidation process systems (0.0338) followed by ozonation-biofiltration (0.0203) and nanofiltration membranes (-0.0022). The stability analysis and comparison studies with other MCDM techniques increase the dependability and consistency of the obtained rankings. The proposed technique provides an explicit and uncertainty-aware basis for ranking tertiary alternatives to treatment and could assist wastewater utilities and regulators in integrating technical decisions with sustainability and water reuse objectives.

PMID:42837953 | DOI:10.1016/j.jenvman.2026.131057

Pediatr Res. 2026 Oct 6. doi: 10.1038/s41390-026-05466-7. Online ahead of print.

ABSTRACT

BACKGROUND: Exposure to non-persistent endocrine-disrupting chemicals (EDCs), including phenols and phthalates, has been linked to obesity risk. While many studies focus on single-chemical exposures, mixture effects on child adiposity remain unclear.

OBJECTIVES: To assess associations of prenatal phenol and phthalate exposures, singly and as mixtures, with early childhood BMI in the U.S. Environmental influences on Child Health Outcomes (ECHO) Program.

METHODS: We included 586 mother-child pairs from three ECHO sites with 23 phenols and phthalate metabolites measured in maternal urine during pregnancy, and child BMI z-scores (BMIZ) at 2-5 years. Associations were estimated using covariate-adjusted single-pollutant linear regression and two mixture methods: Bayesian Weighted Quantile Sum (BWQS) and Bayesian Kernel Machine Regression (BKMR). Sex-specific effects were examined in stratified models.

RESULTS: No associations were observed between the overall prenatal EDC mixture and BMIZ. In single-pollutant models, MBzP (highest tertile) was inversely associated with BMIZ (β = -0.36, 95% CI: -0.63, -0.08), while MEP (second tertile) was positively associated (β = 0.27, 95% CI: 0.01, 0.53). Among boys, MBP (second tertile) was positively associated (β = 0.45, 95% CI: 0.11, 0.79).

CONCLUSIONS: We found no strong evidence for mixture effects, though some individual compounds showed non-linear and sex-specific associations.

IMPACT: Using a 23-analyte panel of phenols and phthalate metabolites, and complementary (BKMR, BWQS) alongside single-pollutant and sex-stratified models, this study strengthens inference and addresses limitations of prior research. Prenatal exposure to ubiquitous, short-lived endocrine-disrupting phthalates showed non-monotonic, sex-specific associations with early childhood BMI in single-pollutant models. These findings contribute to the limited evidence base on mixture effects of endocrine-disrupting chemicals in early-life obesity risk.

PMID:42839036 | DOI:10.1038/s41390-026-05466-7

Environ Sci Pollut Res Int. 2026 Oct 6. doi: 10.1007/s11356-026-38277-8. Online ahead of print.

ABSTRACT

This study investigates the competitive removal of three co-existing estrogens, estrone (E1), 17β-estradiol (E2), and 17α-ethinylestradiol (EE2), from aqueous matrices via batch adsorption. Pre- and post-carbonized materials synthesized from industrial almond shell and cork residues were evaluated under multicomponent conditions. Thermal activation via carbonization proved ineffective, whereas raw cork ("in natura," CiN) exhibited the optimal performance. At 25 °C and an adsorbent dosage of 1.0 g/L, CiN achieved a cumulative mean estrogen removal efficiency of 66.1%. The maximum experimental uptake capacities for E1, E2, and EE2 were 3.82, 3.75, and 7.23 mg/g, respectively, yielding a notable combined capacity of 14.79 mg/g. Kinetic profiles were accurately described by the pseudo-second-order (PSO) model, which predicted an equilibrium time of 440 min at 25 °C. The multicomponent Sheindorf-Rebuhn-Sheintuch (SRS) isotherm model successfully simulated the competitive equilibrium data. Operational parameters showed that highly alkaline media (pH ≥ 12) led to a significant decline in uptake capacity due to electrostatic repulsion. Thermodynamic analysis confirmed that the sequestration process is spontaneous ( ${\Delta G}^0<0$ ), exothermic ( ${\Delta H}^0<0$ ), and entropically favorable ( ${\Delta S}^0>0$ ) at the solid-liquid interface. Comprehensive mechanistic evaluation identified a synergistic interplay between physisorption via pore filling and chemisorption governed by p-electron donor-acceptor interactions and hydrogen bonding networks. The superior competitive affinity of the synthetic estrogen (EE2) was successfully rationalized by its higher hydrophobicity and lower activation energy barrier. Overall, this work highlights the viability of sustainable raw cork residues for environmental remediation, demonstrating that surface chemistry can play a more decisive role than texturized porosity in sequestering endocrine-disrupting chemicals.

PMID:42839166 | DOI:10.1007/s11356-026-38277-8

iScience. 2026 Sep 25;29(10):117274. doi: 10.1016/j.isci.2026.117274. eCollection 2026 Oct 16.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are exogenous agents that target hormone biosynthesis, cellular signaling, transport, metabolism, and receptor activity. Exposure to EDCs is linked to reproductive problems, abnormalities in infant development, neurological impairment, thyroid disorders in women, and hormone-regulated cancers. EDCs are also known to contaminate aquatic and wildlife ecosystems via bioaccumulation, environmental persistence, and disruption of biological processes. To overcome the drawbacks of conventional techniques, researchers developed metal-organic frameworks (MOFs) for water remediation. MOFs are superior materials because they have high surface area, tunable pore structure, chemical versatility, and catalytic capabilities through functionalization. MOFs have demonstrated strong potential for the sensitive detection and degradation of diverse endocrine-active pollutants, including bisphenols and related micropollutants. In this review, sources, classifications of EDCs, routes of exposure, molecular mechanisms, health effects, and socioeconomic effects of EDCs were discussed with illustrative figures. Therefore, integrating MOFs with water treatment strategies using advanced materials engineering will efficiently reduce EDC contamination.

PMID:42835249 | PMC:PMC13635499 | DOI:10.1016/j.isci.2026.117274

Talanta. 2026 Oct 1;313(Pt A):130702. doi: 10.1016/j.talanta.2026.130702. Online ahead of print.

ABSTRACT

Herein, a mesoporous carbon material was prepared via pyrolysis of a melamine-resorcinol formaldehyde copolymer synthesized in the presence of mesoporous hydroxyapatite (HA) nanostructures, as a hard template. The porous HA nanostructures were prepared through a novel strategy that involved synthesizing calcium carbonate nanostructures on CTAB micellar aggregations as a soft template, followed by carbonate-phosphate replacement under hydrothermal conditions. This approach yielded microspheres composed of rod-like nanostructures featuring ordered approximately 1 nm nanochannels, exhibiting a BET surface area of 51.17 m² g^-1 and a BJH-derived characteristic pore diameter of 18.46 nm. The XRD analysis of the carbon product indicated the presence of a graphitic carbon structure, consistent with the Raman spectroscopy results. Additionally, the presence of oxygen and nitrogen heteroatoms and their related functional groups in the carbon framework was confirmed by elemental analysis and FT-IR spectroscopy. Based on BET analysis, the carbon product exhibited a high specific surface area of 882.78 m² g^-1, a large pore volume of 3.944 cm³ g^-1, and a characteristic pore diameter of 32.58 nm obtained from BJH analysis. BET analysis highlighted the role of CTAB and carbonate in the synthesis of the HA template, enabling the achievement of high-surface-area mesoporous carbon. The combination of high porosity, graphitic domains, and oxygen- and nitrogen-containing species makes the material a promising adsorbent for the extraction of relatively polar aromatic compounds. The synthesized carbon material was employed as an effective adsorbent for the dispersive solid-phase extraction (SPE) of some parabens, preservatives with endocrine-disrupting effects, with detection using HPLC-UV. The experimental design methodology efficiently determined optimal extraction conditions while minimizing the number of experiments and analyzing parameter interactions. Under the optimized conditions, a good analytical performance for the proposed method was achieved with a linearity of 0.1-100.0 μg L^-1 (R² ≥ 0.998) and preconcentration factors ranging from 84 to 116 for the target analytes. The applicability of the proposed method was assayed in real samples with different matrices, yielding satisfactory relative recoveries (89-111%) and RSD values (n = 3) ranging from 2.4% to 7.9%.

PMID:42837780 | DOI:10.1016/j.talanta.2026.130702

Mater Today Bio. 2026 Sep 18;41:103690. doi: 10.1016/j.mtbio.2026.103690. eCollection 2026 Dec.

ABSTRACT

Dental caries is one of the most prevalent chronic diseases worldwide, with most lesions occurring in occlusal pits and fissures. To prevent occlusal caries, pit and fissure sealants are considered one of the most effective measures. However, their anticaries effect are often compromised by secondary caries resulting from biofilm accumulation. Furthermore, traditional sealants based on bisphenol A glycidyl methacrylate (Bis-GMA) may release bisphenol A (BPA), raising concerns about potential endocrine disruption. In this study, we developed a bio-based superhydrophobic pit and fissure sealant by utilizing isosorbide dimethacrylate (IM) as a bio-based resin matrix, fluorinated methacrylate (FMA) as a low-surface-energy component, and a combination of micro- and nano-sized SiO₂ to construct a micro-nano hierarchical surface architecture, after light curing treatment. The bio-based micro-nano structured superhydrophobic pit and fissure sealant (m-n SUP) retained superhydrophobicity after immersion in artificial saliva for 5 days, thermocycling for 5000 cycles, pH cycling for 5000 cycles, tape peeling for 100 cycles, and sandpaper abrasion for 40 cycles. m-n SUP also exhibited favorable mechanical properties and enamel bonding comparable to those of the commercial sealant, together with favorable marginal sealing performance. Moreover, m-n SUP exhibited good cytocompatibility, and markedly reduced salivary mucin adsorption and provided sustained inhibition of the initial adhesion and biofilm formation for five representative oral cariogenic bacteria over 72 h. In a rat model, m-n SUP effectively reduced the incidence and severity of occlusal carie. Overall, this bio-based superhydrophobic pit and fissure sealant can provide a promising bio-based material strategy for pit and fissure caries prevention.

PMID:42831082 | PMC:PMC13634338 | DOI:10.1016/j.mtbio.2026.103690

PLoS One. 2026 Oct 5;21(10):e0359940. doi: 10.1371/journal.pone.0359940. eCollection 2026.

ABSTRACT

Bisphenol A (BPA), a widespread environmental endocrine disruptor, can cross the blood-brain barrier and exert neurotoxic effects closely associated with depression pathogenesis. However, the precise molecular targets and signaling pathways mediating BPA-induced depression remain poorly understood. This study integrated network toxicology, molecular docking, molecular dynamics simulation, GEO transcriptomic dataset analysis, and in vivo experimental validation in mice to systematically investigate the potential toxicological targets and underlying mechanisms of BPA in depression. BPA-related targets were predicted from ChEMBL, STITCH, and SwissTargetPrediction, and depression-associated targets were retrieved from GeneCards, OMIM, and TTD databases. Overlapping targets were subjected to PPI network construction, as well as GO and KEGG enrichment analyses. Molecular docking and 100 ns molecular dynamics simulations were performed to verify the binding affinity and structural stability between BPA and hub targets. A total of 29 overlapping targets were screened, which were significantly enriched in neural synaptic function, neurotransmitter binding, and the neuroactive ligand‑receptor interaction pathway. Five core hub genes including INS, ESR1, SLC6A4, GRIA1, and NTRK2 were identified, all of which exhibited stable specific binding to BPA with favorable binding free energies. Further validation based on multiple GEO datasets confirmed that these five core genes were markedly downregulated in MDD patients, accompanied by significant suppression of neurotrophic and insulin-related pathways. In vivo animal experiments further demonstrated that BPA exposure aggravated depressive-like behaviors in mice and significantly downregulated both mRNA and protein expression of the five core molecules in brain tissues. Collectively, this study identifies key neurotoxicity-related targets and molecular pathways underlying BPA-induced depression, providing a theoretical foundation for future mechanistic investigation and clinical intervention strategies.

PMID:42832521 | PMC:PMC13637905 | DOI:10.1371/journal.pone.0359940

Ecotoxicol Environ Saf. 2026 Oct 1;324:120884. doi: 10.1016/j.ecoenv.2026.120884. Epub 2026 Oct 5.

ABSTRACT

sodium pentachlorophenol (PCP-Na) is one of the persistent organic pollutants (POPs) with high lipophilicity. chlorinated hydrocarbon that exhibits broad-spectrum systemic toxicity, accompanied by severe carcinogenic, teratogenic, and mutagenic risks; however, the molecular basis of its gender-specific pathogenesis remains unclear. In this study, mice were exposed to PCP-Na by intraperitoneal injection for 10 days (2.5, 5, and 10 mg/kg). To elucidate the gender-sensitive endocrine mechanism, we evaluated the expression of AR and ERα in the liver and conducted targeted hormone receptor intervention. The results showed that female mice exhibited significantly enhanced sensitivity to PCP-Na, manifested as early growth retardation, elevated AST activity, and exacerbated hepatocyte apoptosis. From a mechanistic perspective, PCP-Na significantly downregulated ERα expression and abnormally upregulated AR, thereby disrupting the microenvironment of the female liver. Crucially, by inhibiting the AR signaling pathway in males and activating ERα in females, the liver damage caused by PCP-Na was successfully alleviated. These findings indicate that due to the specific damage to the natural steroid hormone receptor network by this toxic substance, female mammals are particularly sensitive to PCP-Na. Ultimately, this study provides a mechanistic basis for the use of precise and gender-stratified drug treatment in clinical treatment of environmental toxins.

PMID:42833034 | DOI:10.1016/j.ecoenv.2026.120884

Proc Natl Acad Sci U S A. 2026 Oct 13;123(41):e2608919123. doi: 10.1073/pnas.2608919123. Epub 2026 Oct 5.

ABSTRACT

Toxicity prediction remains a longstanding challenge in the safety assessment of numerous artificial chemicals. While conventional single-endpoint models are effective for predicting many molecular properties, they fail to capture the complex mechanisms underlying toxicity, which involve multiple molecular targets, interconnected pathways, and diverse outcomes. We present a causality-integrated graph learning framework that embeds toxicological mechanisms extracted from large-scale literature mining as directed graphs within deep learning (DL) models. By using chemical structure as input, the framework generates compound-specific perturbation profiles within a fixed causal space, enabling system-level classification, quantitative prioritization, and mechanistic interpretation across multiple outcomes. Focusing on endocrine-disrupting chemicals, we constructed a large-scale, causally organized knowledge graph (EDKG) and implemented the framework as EDKG-DL, a predictive model that incorporates mechanism-aware graph reasoning. Through extensive external validations, EDKG-DL outperforms structure-driven state-of-the-art approaches in both stability and cross-scenario generalization. This work establishes a mechanism-constrained, causality-informed learning paradigm that is highly relevant for multi-endpoint toxicity assessment and regulatory decision-making.

PMID:42832660 | PMC:PMC13663764 | DOI:10.1073/pnas.2608919123

J Adv Res. 2026 Oct 5:S2090-1232(26)00767-8. doi: 10.1016/j.jare.2026.10.006. Online ahead of print.

ABSTRACT

INTRODUCTION: Microalgae are vital primary producers in aquatic ecosystems yet increasingly threatened by nonylphenol (NP), a common endocrine disruptor. Current ecotoxicological assessments, however, largely rely on single-species models, overlooking the role of the phycosphere microbiome in host stress adaptation.

METHODS: Here, using the NP-tolerant microalgae Dictyosphaerium sp. as a model holobiont, we integrated multi-omics, axenic algae-bacteria co-culture, physiological, and metabolic analyses to unravel how associated microbes contribute to microalgal NP fitness.

RESULTS: Under environmentally relevant NP concentrations (10-900 µg/L), the holobiont sustained 20.3-91.3% higher biomass than axenic cultures. NP exposure reshaped the phycosphere community, enriching beneficial taxa. Among 16 bacterial isolates, Brevundimonas sp. D-1 exerted the strongest protective effect, boosting algal biomass by 39.9%. Mechanistically, D-1 significantly accelerated NP removal (P < 0.05), achieving a 28.8% increase within 4 days. Oxidative stress in NP-exposed algae was also markedly achieved, as reflected by 29.3% and 46.8% reductions in reactive oxygen species and malondialdehyde levels, respectively, alongside ultrastructural preservation and > 1.3-fold increases in photosynthetic pigment contents. Moreover, D-1 modulated extracellular polymeric substances, restraining their overproduction while enriching tyrosine- and tryptophan-like components to reinforce the interfacial barrier. Transcriptomic profiling further revealed downregulation of stress-defense genes (e.g., DNA repair and photoprotection) and restoration of growth-related pathways, including photosynthesis and energy metabolism.

CONCLUSION: Our findings establish a community-to-strain paradigm for phycosphere microbiome-mediated tolerance of microalgae to NP, deepen our understanding of inter-species cooperation, and provide a basis for designing tailored algae-bacteria consortia for bioremediation.

PMID:42833601 | DOI:10.1016/j.jare.2026.10.006