Endocrine Disruption

A Case Series of Hypogonadism in 22q11.2 Deletion Syndrome: Is It Time to Check the Gonadal Axis? - November 30, 2025

J Investig Med High Impact Case Rep. 2025 Jan-Dec;13:23247096251385386. doi: 10.1177/23247096251385386. Epub 2025 Nov 29.

ABSTRACT

22q11.2 deletion syndrome is a multifaceted disorder most characterized by congenital cardiac anomalies, immunodeficiency, and psychiatric conditions. Endocrine abnormalities such as hypoparathyroidism and growth hormone deficiency are well documented, but hypogonadism remains rarely reported in this patient population. Only 1 case of hypogonadism has been reported in a patient with multiple other comorbidities which may have contributed to the condition. The relationship between 22q11.2 deletion syndrome and hypogonadism is not well understood. We report 2 male patients with 22q11.2 deletion syndrome and low testosterone levels. The first patient was a 25-year-old male with Tetralogy of Fallot and hypoparathyroidism who presented with balanitis and was found to have low testosterone. Evaluation for causes, including pituitary imaging and hormone panels, was unremarkable. The second patient was a 20-year-old male with a history of growth hormone deficiency and hypogonadism, scoliosis, and neurodevelopmental disorders who had low testosterone levels. No identifiable causes were found. Mechanisms include disruptions in the hypothalamic-pituitary-gonadal axis during embryonic development or testicular dysfunction. Impaired function of synaptosomal-associated protein 29, a gene located within the 22q11.2 region, may contribute to testosterone deficiency. The rarity of reported hypogonadism in 22q11.2 deletion syndrome suggests that it may be underdiagnosed due to a lack of routine screening protocols. Further studies evaluating testosterone, LH, and FSH levels in this population are warranted to establish prevalence and determine whether routine endocrine assessment should be incorporated into clinical guidelines.

PMID:41319030 | DOI:10.1177/23247096251385386

Key lncRNA-mRNA networks regulated by Polyascus sp. infection: A comparative transcriptomic analysis of the eyestalk in the Eriocheir sinensis - November 29, 2025

Comp Biochem Physiol Part D Genomics Proteomics. 2025 Nov 22;57:101693. doi: 10.1016/j.cbd.2025.101693. Online ahead of print.

ABSTRACT

The Chinese mitten crab (Eriocheir sinensis) is a crustacean widely distributed in coastal and estuarine waters across China. Due to its high nutritional value, it has become a significant commercial aquaculture species in China, generating substantial economic value. Polyascus sp., which is called crab slave, can parasitize on crabs, altering the host's morphological appearance and disrupting its endocrine regulation, thereby inhibiting growth and development. To further elucidate the molecular mechanisms underlying the host crab's response to crab slave parasitism and to elucidate the role of lncRNAs in this process, we performed comparative transcriptome sequencing analysis on the eyestalk tissues of parasitized and non-parasitized crabs. This study identified 2746 novel lncRNAs, including 735 differentially expressed lncRNAs in the male comparison groups and 394 differentially expressed lncRNAs in the female comparison groups. Concurrently, GSEA analysis of target mRNAs for differentially expressed lncRNAs revealed that Polyascus sp. parasitism influences lncRNA regulation of GO:0042302 (structural components of the cuticle), GO:0006040 (amino acid metabolism processes), and GO:0006030 (chitin metabolic process) were enriched in the male comparison (T1 vs. CK1), while GO:0044282 (small molecule catabolic process) and GO:0016627 (oxidoreductase activity, acting on the CH-CH group of donors), etc., were enriched in the female comparison (T2 vs. CK2). Furthermore, a molecular regulatory network of key lncRNA-mRNA interactions was constructed based on transcriptomic profiles. These findings provide new insights into lncRNA-mediated physiological regulation in crustaceans and highlight the pivotal role of lncRNAs in modulating expression patterns.

PMID:41317455 | DOI:10.1016/j.cbd.2025.101693

DSN-assisted split aptamer strategy coupled with gold nanoparticle growth for colorimetric detection of estradiol - November 29, 2025

Talanta. 2025 Nov 26;300:129164. doi: 10.1016/j.talanta.2025.129164. Online ahead of print.

ABSTRACT

Estradiol (E2) is a vital hormone and recognized endocrine disruptor that necessitates sensitive monitoring at trace concentrations. While existing analytical methods provide high accuracy, their cost and operational complexity emphasize the need for simpler, yet sensitive alternatives. Here, we report a colorimetric assay for the sensitive detection of E2 by integrating duplex-specific nuclease (DSN) activity with split aptamer recognition and gold nanoparticle (AuNP) growth. In this design, E2 induces the hybridization of split aptamer fragments on AuNP surfaces, which are subsequently cleaved by DSN, leading to shortened surface DNA strands and altered nanoparticle passivation. This process induces heterogeneous gold growth upon gold (III) reduction, producing distinct colorimetric shifts that can be observed visually and quantified spectroscopically. Under optimized conditions, the assay exhibited a linear response in the range of 1-400 ng/mL with a detection limit of 1 ng/mL. This platform exhibited good selectivity against structurally related hormones and other potential interferents. Measurements in spiked human serum showed good agreement with commercial ELISA results, yielding a Pearson correlation coefficient of 0.91. This DSN-assisted split aptamer-AuNP strategy offers a straightforward and sensitive approach for detecting small molecules, with promising potential for clinical diagnostics.

PMID:41317480 | DOI:10.1016/j.talanta.2025.129164

Exploring the impact of endocrine-disrupting chemicals on erectile dysfunction through network toxicology and machine learning - November 29, 2025

BMC Pharmacol Toxicol. 2025 Nov 28;26(1):203. doi: 10.1186/s40360-025-01033-8.

ABSTRACT

BACKGROUND: Erectile dysfunction (ED) is a common male sexual disorder with a multifactorial etiology. The exposure to endocrine-disrupting chemicals (EDCs) has been increasingly linked to reproductive health disorders in both men and women. EDCs can interfere with hormonal signaling and physiological homeostasis, but their specific roles and mechanisms in contributing to ED remain inadequately elucidated.

METHODS: Network toxicology and enrichment analysis were used to identify potential targets and signaling pathways involved in ED induced by EDCs. Single-cell sequencing was conducted to analyze the expression profiles of these targets in corpus cavernosum tissue. Key regulatory molecules were identified through protein-protein interaction (PPI) network analysis. Core targets were selected using three machine learning algorithms to evaluate the association between EDCs and ED. Molecular docking simulations were further employed to verify the binding affinity between EDCs and target proteins, elucidating potential mechanisms of action.

RESULTS: A total of 186 potential targets were identified. Single-cell sequencing revealed their expression characteristics. PPI analysis identified key regulatory molecules, and machine learning approaches pinpointed two core targets: CTNNB1 and HIF1A. Molecular docking confirmed that most EDCs exhibit stable binding to CTNNB1 and HIF1A, suggesting the involvement of associated signaling pathways in the development of ED.

CONCLUSIONS: This study systematically characterizes the molecular pathways through which EDCs contribute to ED, with CTNNB1 and HIF1A emerging as central players. The identification of these core targets provides a theoretical foundation for developing targeted interventions against environment-related ED and underscores the importance of mitigating EDC exposure in public health strategies.

PMID:41316467 | PMC:PMC12661834 | DOI:10.1186/s40360-025-01033-8

Sex-specific association of prenatal exposure to halogenated persistent organic pollutants (Hal-POPs) with neonatal sex hormone levels and birth size: a birth cohort study using meconium as a biomonitoring matrix - November 29, 2025

Environ Int. 2025 Nov 22;206:109953. doi: 10.1016/j.envint.2025.109953. Online ahead of print.

ABSTRACT

Halogenated persistent organic pollutants (Hal-POPs) are endocrine disruptors that posing risks to fetal development via transplacental transfer. This study utilized neonatal meconium, a non-invasive matrix reflecting cumulative exposure during the second- and third-trimester, to assess prenatal levels of per- and polyfluoroalkyl substances (PFASs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs) in 271 mother-infant pairs from Guangzhou, China. The associations between Hal-POP exposure, neonatal sex hormones, and birth size Z-scores [weight (BWZ), length (BLZ), head circumference (HCZ)], as well as the potential hormonal mediation were explored. Results showed ubiquitous Hal-POP detection, with 4:2 fluorotelomer sulfonic acid (4:2 FTSA; median: 0.53 nmol/g), BDE-47 (0.11 nmol/g), and p, p'-DDE (0.04 nmol/g) being the dominant chemicals within their respective classes. 4:2 FTSA levels were higher in male neonates (p < 0.05). Generalized linear models (GLMs) revealed sex-specific endocrine association of 4:2 FTSA, elevating androgens [testosterone (T) and dihydrotestosterone (DHT)] and reducing estrogens [estrone (E1) and estriol (E3)] and progesterone (P4) in males, whereas only decreasing E1 modestly in females. Bayesian Kernel Machine Regression (BKMR) identified PFASs (Group-PIP ≥ 0.98) as the primary contributors to elevated androgen (T and DHT) and reduced E3, with 4:2 FTSA as the key driver (Cond-PIP ≥ 0.95). Mediation analyses revealed that both E1 and E3 mediated 22.2 % of the negative association between 4:2 FTSA and BLZ. Sex-stratified analyses showed E3 mediated 22.8 % of this relationship in males, while exerted a suppression effect on the 4:2 FTSA-HCZ associations in females. Molecular docking revealed that 4:2 FTSA exhibits high-affinity binding to key steroidogenic enzymes (including CYP19A1, 17β-HSD1, AKR1C2, and AKR1C3), suggesting direct disruption on steroid hormone synthesis. This study highlights the endocrine-disrupting potential of emerging PFAS alternatives and their sex-specific effects on fetal growth, providing critical evidence for targeted strategies to reduce prenatal Hal-POP exposure and associated developmental risks.

PMID:41317605 | DOI:10.1016/j.envint.2025.109953

Exposure to environmental xenobiotics and lung tissue function: A comprehensive review on biological mechanisms and pathways - November 29, 2025

Ecotoxicol Environ Saf. 2025 Nov 28;308:119438. doi: 10.1016/j.ecoenv.2025.119438. Online ahead of print.

ABSTRACT

Environmental xenobiotics, encompassing a wide spectrum of chemical pollutants such as particulate matter-bound polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), persistent organic pollutants (POPs), heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, and emerging contaminants like nanomaterials and microplastics, have been increasingly implicated in impairing lung tissue function. These agents enter the body primarily through inhalation, particularly via outdoor air pollution, indoor contaminants, and occupational exposures, with additional contributions from ingestion and dermal absorption. Studies investigating these pollutants employ diverse exposure assessment methods, including environmental and biological monitoring, model-based estimations, and questionnaire-based tools. Lung function assessment spans from clinical spirometry and imaging to experimental histopathology and molecular biomarker analyses. Mechanistic evidence reveals that xenobiotics induce lung injury through oxidative stress, inflammation, mitochondrial dysfunction, epithelial barrier disruption, and epigenetic alterations. These processes lead to chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and lung cancer. Key signaling pathways implicated include activation of NF-κB, AP-1, and the aryl hydrocarbon receptor (AhR), promoting pro-inflammatory and cytotoxic responses. Furthermore, pollutant-induced epithelial permeability and fibrotic remodeling via TGF-β signaling exacerbate lung tissue damage and functional decline. While spirometry is widely used in population studies, it lacks sensitivity for early pathophysiological changes, necessitating integration with molecular and imaging approaches. Experimental models and in vitro studies provide valuable mechanistic insight, though challenges remain in translating findings to human populations. Current research underscores the complexity of real-world exposure scenarios and highlights the need for harmonized, multidisciplinary approaches combining environmental, biological, and molecular data. This comprehensive review synthesizes evidence across epidemiological and experimental studies, aiming to elucidate the biological pathways by which xenobiotic exposure compromises lung tissue function and to inform future research and regulatory strategies.

PMID:41317616 | DOI:10.1016/j.ecoenv.2025.119438

Sex-specific reproductive toxicity of polystyrene nanoplastics and DEHP in adult zebrafish (Danio rerio) - November 29, 2025

Ecotoxicol Environ Saf. 2025 Nov 28;308:119488. doi: 10.1016/j.ecoenv.2025.119488. Online ahead of print.

ABSTRACT

Micro- and nanoplastics (MNPs) and di(2-ethylhexyl) phthalate (DEHP) are ubiquitous environmental contaminants; however, the risks of their combined exposure to aquatic reproductive health, particularly sex-specific differences, remain incompletely understood. This study investigated the effects of single and combined exposure to polystyrene nanoplastics (PS-NPs; 0.1 and 1 mg/L) and DEHP (10 μg/L) on the reproductive endocrine system of adult male and female zebrafish (Danio rerio) Results demonstrated that PS-NPs accumulated in the zebrafish intestine. High concentrations of PS-NP and DEHP and their combined exposures induced significant adverse effects in both sexes, including gonadal tissue damage and oxidative stress. A striking sexual dimorphism was observed in endocrine responses. Females exhibited a pronounced suppression of both 17β-estradiol (E2) and testosterone (T) levels, which correlated with inhibited ovarian cyp19a gene expression under co-exposure. Conversely, male E2 levels remained stable and T levels decreased only under co-exposure, increasing E2/T ratio. This distinct male endocrine profile was associated with differential regulation of testicular cyp19a and 17β-hsd expression. This study confirms that PS-NPs and DEHP exert profound sex-specific reproductive toxicity in zebrafish. These effects are mediated by disrupting the hypothalamic-pituitary-gonadal (HPG) axis, while inducing sex-specific alterations in brain and gonadal gene expression. Overall, this study highlights the critical importance of considering sex differences and pollutant mixture effects in environmental risk assessments.

PMID:41317617 | DOI:10.1016/j.ecoenv.2025.119488

Sorption behavior of 17α-Ethynylestradiol at the soil colloid/solution interface from different sources: Influence of organic/inorganic components and hydrochemical conditions - November 29, 2025

Environ Res. 2025 Nov 27:123444. doi: 10.1016/j.envres.2025.123444. Online ahead of print.

ABSTRACT

The interfacial interaction between colloids and endocrine disrupting chemicals EDCs significantly regulates their environmental behavior. In particular, how properties of colloids from different sources affect these interaction mechanisms is a key focus in environmental research. This study systematically investigates the interfacial sorption of 17α-Ethinyl Estradiol (EE2) on soil colloids from three pedogenic environments: black soil (BS), cinnamon soil (CS), and loess soil (LS). The interfacial interaction mechanisms were examined with a multi-technique approach (SEM, XPS, XRD, FTIR, BET). Three types of soil colloids have organic and inorganic components. The content of organic colloids serves as the crucial determinant for their interfacial interactions with EE2. Significantly, the hydrophobic partitioning of EE2 into soft carbon fractions emerges as the predominant sorption mechanism. BS exhibits a stronger sorption capacity for EE2 than CS and LS, primarily due to its higher organic matter and soft carbon content. The contribution rate of slow sorption in BS is markedly higher than in LS and CS, due to the greater content of hard carbon in BS, which offers more non-specific sorption sites and a higher quantity of microporous structures, resulting in improved micropore filling. For inorganic colloid components, illite and kaolinite contents mainly affect EE2 interfacial sorption. The -OH group in EE2, along with carboxyl and quinone groups from -OH and acetylene group oxidation, can form complexes with Fe and Al in inorganic colloids by chemical sorption. These findings highlight the potential for EE2 to be transported over long distances in subsurface environments via association with mobile soil colloids, which raises concerns about its persistence and potential to contaminate groundwater resources.

PMID:41317831 | DOI:10.1016/j.envres.2025.123444

Bisphenol A triggers adipocyte dysfunction, thereby fostering triple-negative breast cancer aggressiveness - November 29, 2025

Environ Res. 2025 Nov 27:123446. doi: 10.1016/j.envres.2025.123446. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is an organic compound widely used in the production of polycarbonate plastics and epoxy resins. As a pervasive environmental pollutant, BPA accumulates in adipose tissue (AT) due to its lipophilic properties. AT, an endocrine organ central to homeostasis, constitutes the main component of breast stroma and plays a pivotal role in the microenvironment of breast cancer, including triple-negative breast cancer (TNBC). This study investigated how BPA disrupts adipocyte differentiation and metabolism, and the subsequent effects on the crosstalk between adipocytes and TNBC cells. We induced adipogenic differentiation of preadipocytes in the presence of BPA and evaluated alterations in differentiation and cytokine secretion. TNBC cells were cultured in homotypic and heterotypic organoids, exposing them to BPA either directly or indirectly, through a conditioned medium of BPA-treated adipocytes. BPA exposure altered adipocyte differentiation, reducing lipid accumulation and perturbing cytokines release, leading to the upregulation of molecules involved in cell migration and invasiveness. TNBC cells exposed to conditioned medium of BPA-treated adipocytes exhibited enhanced growth, migration and invasiveness, whereas direct BPA treatment did not induce significant changes. These indirect effects were, at least in part, mediated by SDF1α and GAS1. Moreover, TNBC organoids showed increased infiltrative capacity when co-cultured with BPA-conditioned adipocytes. These findings highlight the profound impact of environmental pollution on cancer progression. BPA perturbates adipose differentiation, creating a dysfunctional adipocyte that fosters cancer growth and invasiveness in TNBC. This study underscores the impact of environmental pollutants on tumour progression by revealing the importance of BPA perturbation on tissue homeostasis and how this could promote cancer.

PMID:41317837 | DOI:10.1016/j.envres.2025.123446

A novel carboxylesterase HylD3 with efficient hydrolytic activity against phthalate esters: Enzymatic characterization, catalytic mechanism, and recycling catalysis through immobilization - November 29, 2025

Bioresour Technol. 2025 Nov 27:133731. doi: 10.1016/j.biortech.2025.133731. Online ahead of print.

ABSTRACT

Phthalate esters (PAEs), widely used as plasticizers, are persistent environmental and food contaminants associated with endocrine disruption and health risks. Enzymatic degradation offers a promising solution, yet the catalytic mechanisms of the sparsely studied family VIII carboxylesterases remain largely unexplored. Here, a novel family VIII carboxylesterase HylD3 was characterized with efficient PAEs hydrolysis performance. Biochemical analysis revealed optimal activity at pH 9.5 and 45 °C but poor thermostability (half-life 0.12 min at 65 °C). Structural bioinformatics and mutagenesis uncovered a non-classical catalytic triad (S79-K82-Y185), while molecular docking and simulations showed that substrate affinity was enhanced by an enlarged active pocket and a reshaped binding energy landscape of the enzyme HylD3, which collectively provided first molecular-level insight into PAEs hydrolysis by this enzyme family. To overcome thermostability limitations, COF-LZU1@HylD3 was prepared via rapid aqueous-phase one-pot immobilization within 10 min. The immobilized system preserved the free enzyme's catalytic properties, exhibited a 21.00-fold improvement in thermostability at 65 °C, and maintained 47.06 % activity after five cycles of catalysis, achieving a sustainable hydrolysis efficiency of 8.22 g/(L·d). This study advances the mechanism understanding of family VIII carboxylesterase in PAEs hydrolysis and establishes a thermostable biocatalytic platform for efficient PAEs detoxification food-related and environmental systems.

PMID:41317923 | DOI:10.1016/j.biortech.2025.133731

Computational toxicology Insights into pyriproxyfen and its transformation products: An overlooked driver of aquatic toxicity and endocrine disruption - November 29, 2025

J Environ Manage. 2025 Nov 28;396:128100. doi: 10.1016/j.jenvman.2025.128100. Online ahead of print.

ABSTRACT

Pyriproxyfen (PPF) is a widely used insect growth regulator that has been detected in aquatic environments. However, the aquatic effects of its transformation products (TPs) remain unclear. In this study, a computational toxicology framework was used to assess the aquatic risks of PPF and its aerobic TPs. Biodegradation simulations predicted 66 aerobic TPs. Toxicity screening showed that over 20 % of these TPs caused significant acute or chronic toxicity to aquatic species, including fish, daphnia, and algae. Risk classification based on species sensitivity distributions (SSD) and maximum acceptable environmental values (MAEV) suggested that the ecological risk of the PPF may be underestimated. Among the TPs, 15 (25.8 %) were categorized as high risk, 10 (15.1 %) as moderate risk, and 18 (27.3 %) as low risk, implying that more than half pose potential ecological threats. Molecular docking showed that 31.8 % of the TPs had binding energies below -5 kcal/mol with estrogen receptors (ER) from 11 aquatic species, suggesting potential estrogenic activity. Besides, PPF-M21, M56, and M61-M64, showed both higher toxicity and strong ER binding. Furthermore, profiling of persistence, mobility, and toxicity (PMT) showed that nearly 90 % of the TPs are highly mobile, increasing their likelihood of environmental exposure. Collectively, these findings highlight PPF TPs as an overlooked but significant source of aquatic endocrine disruption and ecological risk. It is therefore recommended that future regulatory and management strategies incorporate TP-focused monitoring and risk assessment to better safeguard aquatic ecosystems.

PMID:41317558 | DOI:10.1016/j.jenvman.2025.128100

Exposure to environmental xenobiotics and lung tissue function: A comprehensive review on biological mechanisms and pathways - November 29, 2025

Ecotoxicol Environ Saf. 2025 Nov 28;308:119438. doi: 10.1016/j.ecoenv.2025.119438. Online ahead of print.

ABSTRACT

PMID:41317616 | DOI:10.1016/j.ecoenv.2025.119438

Environ Int. 2025 Nov 22;206:109953. doi: 10.1016/j.envint.2025.109953. Online ahead of print.

ABSTRACT

PMID:41317605 | DOI:10.1016/j.envint.2025.109953

Assessing the Neurotoxicity of Bisphenol A Using Network Toxicology, Molecular Docking, and Molecular Dynamics Simulation - November 29, 2025

Int J Toxicol. 2025 Nov 28:10915818251396291. doi: 10.1177/10915818251396291. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a prevalent environmental endocrine disruptor with potential impacts to the neurological system in humans. This study used an integrated method combining network toxicology, molecular docking, and molecular dynamics simulations to explore the molecular mechanisms underlying BPA-induced neurotoxicity. We identified 255 potential neurotoxicity-related targets through the integration and comprehensive analysis of multiple data sources, including the Comparative Toxicogenomics Database (CTD), ChEMBL, STITCH, GeneCards, and the Online Mendelian Inheritance in Man (OMIM) database. Analysis of the protein-protein interaction (PPI) network unveiled 52 core targets, among which TNF, TP53, INS, ESR1, and PTGS2 emerged as pivotal hubs in the toxicity network. Functional enrichment analysis indicated that the core targets of BPA's influence on neurotoxicity are predominantly enriched in vital signaling cascades, including inflammatory responses, pathways of neurodegeneration, MAPK signaling pathway, serotonergic synapse pathway, and pathways in cancer. Molecular docking results demonstrated that BPA exhibited stable binding interactions with core targets. Furthermore, molecular dynamics simulations provided insights into the interactions between BPA and key targets (ESR1, TNF, and TP53), supporting the potential conformational stability of these complexes. Collectively, these computational findings contribute to understanding the potential molecular mechanisms of BPA-induced neurotoxicity and are informative for generating hypotheses related to its pathogenesis.

PMID:41316712 | DOI:10.1177/10915818251396291

Computational toxicology Insights into pyriproxyfen and its transformation products: An overlooked driver of aquatic toxicity and endocrine disruption - November 29, 2025

J Environ Manage. 2025 Nov 28;396:128100. doi: 10.1016/j.jenvman.2025.128100. Online ahead of print.

ABSTRACT

PMID:41317558 | DOI:10.1016/j.jenvman.2025.128100

Occurrence Characteristics of Microplastics in Aquatic Environments and Their Environmental Ecological Risk Assessment - November 29, 2025

Huan Jing Ke Xue. 2025 Nov 8;46(11):6917-6929. doi: 10.13227/j.hjkx.202408148.

ABSTRACT

Microplastics (MPs) are persistent pollutants that are resistant to degradation and can persist in the environment for extended periods, exerting negative impacts on ecosystems. Through Meta-analysis, the distribution of MPs in domestic and international water bodies was comprehensively analyzed based on representative data extracted from the literature. This data included occurrence characteristics such as abundance, shape, size, color, and composition of MPs in marine, river, and lake water bodies. The results indicated that marine, riverine, and lacustrine systems across the globe are subjected to varying degrees of MP pollution. The predominant components identified were polyethylene, polypropylene, polyethylene terephthalate, polyvinyl chloride, and polystyrene, with black, white, and transparent colors being the most common. The particle sizes of MPs were largely distributed within the range of 0-1 mm. The Tukey's test revealed significant differences in MP abundance between marine and freshwater systems (P < 0.05), while no significant differences were observed between riverine and lacustrine systems. MPs were concentrated in areas of intense human activity, with primary sources including fishing activities, plastic waste degradation, laundry, and personal care products. Spatial and temporal variations in MP distribution were attributed to factors such as monsoon currents, geographic location, and water flow direction. MPs were also found to be ingested and accumulated by aquatic organisms, leading to oxidative stress, neurotoxicity, endocrine disruption, and immune damage, which negatively affected metabolism and reproduction. A total of 38 studies on the ecological risk assessment of MPs in aquatic environments were synthesized to evaluate the applicability, advantages, and limitations of current assessment methods. The findings indicated that the ecological risks of MPs in aquatic systems were predominantly classified as levels Ⅰ-Ⅲ, with MP abundance and polymer toxicity being the primary factors influencing overall risk levels. Finally, future research directions were proposed for studying the occurrence characteristics and ecological risk assessment of MPs in aquatic environments.

PMID:41316757 | DOI:10.13227/j.hjkx.202408148

Occurrence Characteristics of Microplastics in Aquatic Environments and Their Environmental Ecological Risk Assessment - November 29, 2025

Huan Jing Ke Xue. 2025 Nov 8;46(11):6917-6929. doi: 10.13227/j.hjkx.202408148.

ABSTRACT

PMID:41316757 | DOI:10.13227/j.hjkx.202408148

Evaluating the Endocrine-Disrupting and Oxidative Stress Potential of a 50-Component Human-Relevant Complex Chemical Mixture Using In Vitro Tests - November 29, 2025

J Appl Toxicol. 2025 Nov 29. doi: 10.1002/jat.70011. Online ahead of print.

ABSTRACT

Humans are chronically exposed to mixtures of environmental contaminants. Exposure to endocrine-disrupting chemicals (EDCs) contributes to increased health impairment observed globally. This study aimed to evaluate the endocrine-disruptive and oxidative stress potential of a human-relevant, complex chemical mixture in vitro. By testing chemical class subgroup mixtures, the identity of toxicological drivers and mixture additivity could be investigated. A 50-component mixture was compiled based on Swedish human blood concentrations (xHBC), consisting of six subgroup mixtures: polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (PCB mixture), brominated flame retardants (BFR mixture), per- and polyfluoroalkyl substances (PFAS mixture), pesticide mixture, synthetic phenolic contaminants (phenol mixture), and phthalate mixture. These were tested in four chemically activated luciferase gene expression (CALUX) assays: dioxin responsive (DR-), estrogen receptor α (ERα-), androgen receptor. (AR-), and nuclear factor erythroid 2-related factor 2 (Nrf2)-CALUX, along with an adipocyte cell assay. The total mixture caused significant agonistic activity in DR- and ER-, and antagonistic activity in AR-CALUX at 0.1-15 xHBC, depending on the assay. Mixture additivity was assessed in ERα-, DR-, and anti-AR-CALUX using subgroup mixtures and the concentration addition (CA) model. The total mixture followed the CA model in ERα-, anti-AR- and DR-CALUX. The toxicological drivers of these activities were mainly the PCB and phenol mixture. A significant increase in differentiated adipocytes was observed at 100 xHBC. These results raise concerns regarding potential health effects on the endocrine system. The additive effects at human-relevant concentrations observed in this study motivate considering mixtures in regulatory contexts to protect the well-being of future generations.

PMID:41317044 | DOI:10.1002/jat.70011

Evaluating the Endocrine-Disrupting and Oxidative Stress Potential of a 50-Component Human-Relevant Complex Chemical Mixture Using In Vitro Tests - November 29, 2025

J Appl Toxicol. 2025 Nov 29. doi: 10.1002/jat.70011. Online ahead of print.

ABSTRACT

PMID:41317044 | DOI:10.1002/jat.70011

Assessing the Neurotoxicity of Bisphenol A Using Network Toxicology, Molecular Docking, and Molecular Dynamics Simulation - November 29, 2025

International Journal of Toxicology, Ahead of Print.
Bisphenol A (BPA) is a prevalent environmental endocrine disruptor with potential impacts to the neurological system in humans. This study used an integrated method combining network toxicology, molecular docking, and molecular dynamics simulations to ...

Assessing the Neurotoxicity of Bisphenol A Using Network Toxicology, Molecular Docking, and Molecular Dynamics Simulation - November 29, 2025

Anchoring single-atom iron sites onto carbon spheres for boosting electrochemical sensing of bisphenol A - November 28, 2025

Talanta. 2025 Nov 27;300:129158. doi: 10.1016/j.talanta.2025.129158. Online ahead of print.

ABSTRACT

Bisphenol A (BPA), a common endocrine-disrupting chemical, poses serious threats to both ecological systems and human health even at trace concentrations. However, the accurate detection of BPA in complex matrices remains challenging due to the low sensitivity and poor selectivity of conventional electrochemical sensing platforms. The saturated N₄-coordinated single-atom sites derived from metal phthalocyanines exhibit high catalytic specificity and atomic utilization efficiency, enabling selective recognition of BPA. These characteristics enhance adsorption and electron transfer processes, potentially overcoming the limitations of traditional sensing materials and offering a feasible route for the ultra-sensitive detection of trace BPA in complex environments. In this study, we have developed a highly efficient electrochemical sensor for BPA by anchoring saturated N₄-coordinated single-atom sites of metal phthalocyanine onto carbon spheres (MPc/CSs, where M = Fe, Co, and Ni). The carbon spheres (CSs) serve as substrates to support the metal phthalocyanine molecules, improving the stability of the active sites and preventing aggregation. Among the materials tested, FePc/CSs exhibited the highest sensitivity (0.53 μA μM^-1) and the lowest limit of detection (0.031 μM), exhibiting better performance than other modified electrodes, including CoPc/CSs, NiPc/CSs, and metal-free phthalocyanine-loaded CSs (H₂Pc/CSs). Structural analysis revealed that the Fe-N₄ single-atom sites possess higher charge density than the Co-N₄ and Ni-N₄ single-atom sites, resulting in their superior catalytic activity. Practical validation of the FePc/CSs modified glassy carbon electrode (GCE) in real samples, such as supermarket receipts and plastic products, yielded satisfactory recovery rates (97.5-103.4 %), confirming the sensor's reliability in complex matrices. These results demonstrate that electrodes based on CSs-supported single-atom iron sites can serve as highly sensitive, selective, and cost-effective electrochemical sensors for BPA. Overall, this work provides an efficient strategy for designing high-performance environmental sensors based on engineered electronic microenvironments and offers valuable insights for the sensitive analysis of environmental pollutants.

PMID:41313826 | DOI:10.1016/j.talanta.2025.129158

Parental exposure to hexafluoropropylene oxide trimer acid induces transgenerational developmental toxicity and thyroid endocrine disruption effects in zebrafish - November 28, 2025

Ecotoxicol Environ Saf. 2025 Nov 27;307:119476. doi: 10.1016/j.ecoenv.2025.119476. Online ahead of print.

ABSTRACT

Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid, has been ubiquitously detected in aquatic environment. However, the current understanding of its transgenerational toxicity in fish and the underlying mechanisms remains scarce. Therefore, in this study, adult zebrafish (F0) were exposed to HFPO-TA at concentrations of 0, 0.5, 5, and 50 μg/L for 90 days, and transgenerational developmental toxicity and thyroid disruption effects across three generations were investigated. The results revealed that parental HFPO-TA exposure induced significant reductions of the heart rate and swirl-escape rate in unexposed F1 and F2 offspring, which could be induced by dysregulating genes involved in the central nervous system development and associated with the thyroid hormone (TH) disorders. Furthermore, histological changes of thyroid follicles, disruptions of TH homeostasis and transcriptional expressions of key genes involved in the hypothalamic-pituitary-thyroid axis, and DNA methylation modifications in the promoter of two key genes, were observed across three generations. These suggested that parental HFPO-TA exposure could dysregulate the gene expressions via disrupting DNA methylation in the promoters, and consequently induced the adverse effects. Interestingly, the thyroid disruption effects in F1 offspring were associated with maternal transfer of HFPO-TA and promoter methylation of key genes, while the adverse effects in F2 offspring were associated with maternal transfer of THs as well as promoter methylation of key genes. These findings could promote our understanding on transgenerational toxicity induced by HFPO-TA, and adverse effects after the long-term exposure should be given more attention.

PMID:41313981 | DOI:10.1016/j.ecoenv.2025.119476

Environmental Fate of Illicit Drugs and New Psychoactive Substances in Aquatic Systems: Impact, Critical Insights, and Future Directions - November 28, 2025

Environ Toxicol Pharmacol. 2025 Nov 26:104880. doi: 10.1016/j.etap.2025.104880. Online ahead of print.

ABSTRACT

Illicit drugs and novel psychoactive substances (NPS) in aquatic environments pose growing ecological and public health concerns due to their persistence and toxicity. Released mainly via wastewater and runoff, their transport and fate are influenced by microbial degradation, hydrology, and bioaccumulation. These compounds have been detected in freshwater and marine ecosystems, causing endocrine disruption and toxicity in aquatic organisms, with potential human exposure through water and food. Advances in high-resolution mass spectrometry (HRMS) have improved their detection, while treatment technologies such as advanced oxidation, membrane filtration, and bioremediation are being developed to remove these residues. This review integrates findings from environmental chemistry, ecotoxicology, and public health to assess the sources, behavior, impacts, and mitigation of illicit drugs and NPS in aquatic systems. It highlights the complexity of these contaminants and identifies critical knowledge gaps that must be addressed to support effective monitoring, risk assessment, and regulatory strategies.

PMID:41314322 | DOI:10.1016/j.etap.2025.104880

Synergistic effects of bisphenol A and its substitutes with latent insulin resistance on childhood blood pressure and the potential role of lipid metabolism - November 28, 2025

Environ Int. 2025 Nov 22;206:109951. doi: 10.1016/j.envint.2025.109951. Online ahead of print.

ABSTRACT

Childhood hypertension is a growing public health concern, predisposing affected individuals to long-term cardiovascular complications. The cardiovascular and metabolic effects of exposure to bisphenol A (BPA) substitutes, emerging endocrine-disrupting chemicals, remain poorly understood in children. This study investigated associations between childhood BPA substitutes exposure and blood pressure, focusing on the modifying role of latent insulin resistance (LIR) and potential lipid metabolic pathways. A total of 747 children from a prospective cohort in Xiamen, China, were included. Associations between repeated bisphenol measurements and blood pressure were assessed using mixed-effects models and generalized estimating equations. A random subsample underwent lipidomic profiling; participants were grouped by bisphenol exposure and triglyceride-glucose (TyG) index. Differentially expressed lipids were identified, tested for associations with blood pressure, and analyzed by enrichment and mediation approaches. Exposure to bisphenol AF and AP was positively associated with higher systolic blood pressure z-scores (β = 0.075 and 0.144, both P < 0.001) and with increased risk of elevated and high blood pressure (OR = 1.218 and 1.364, P < 0.001 and = 0.002; OR = 1.281 and 1.539, both P < 0.001). Children with concurrently higher bisphenol AF or AP exposure and TyG exhibited lipid dysregulation, which was associated with increased childhood blood pressure. Dysregulated lipids were predominantly enriched in lysoglycerophospholipids and lipid-mediated signaling pathways. Specific lipids, including two glycerolipids and five glycerophospholipids, potentially mediated the association between bisphenol AF/AP × LIR and blood pressure, with indirect effects ranging from 0.114 to 0.626. In conclusion, bisphenol AP and AF were significantly associated with elevated childhood blood pressure. LIR amplified these adverse effects, partly through lipidomic perturbations, highlighting glycerophospholipid and glycerolipid metabolism as potential pathways underlying this association.

PMID:41314138 | DOI:10.1016/j.envint.2025.109951

Plastic associated endocrine disruptors reduce Nicastrin protein and potentiate inflammation in hidradenitis suppurativa skin disease - November 28, 2025

Nat Commun. 2025 Nov 28;16(1):10755. doi: 10.1038/s41467-025-65789-7.

ABSTRACT

Hidradenitis Suppurativa (HS) is an inflammatory skin disorder with limited treatments and unclear etiology. While monogenic HS is linked to gamma secretase mutations, particularly in the NCSTN subunit, the pathogenesis of the more common sporadic form remains uncertain, though associated with risk factors such as diets high in ultra-processed foods. Consistent with the clinical overlap between sporadic and monogenic HS, we find loss of NCSTN protein in sporadic HS fibroblasts. We hypothesize the rising incidence of sporadic HS and its hormonal associations implicate endocrine-disrupting chemicals, especially plastic-associated EDCs (p-EDs) common in UPFs. We detect elevated p-ED adducts in HS skin, persisting in ex vivo cultured fibroblasts. At nanomolar concentrations, p-EDs inhibits NCSTN and primes fibroblasts for inflammation, mimicking NCSTN knockdown. These findings suggest p-ED exposure contributes to HS pathogenesis, highlighting the need to address environmental exposures in HS and other gamma secretase-related diseases.

PMID:41315355 | PMC:PMC12663211 | DOI:10.1038/s41467-025-65789-7

The role of sex steroids in the human gut microbiome - November 28, 2025

Curr Opin Pediatr. 2025 Nov 20. doi: 10.1097/MOP.0000000000001527. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Sex steroid hormones and the gut microbiome are increasingly recognized as bidirectionally interacting regulators of growth, metabolism, and endocrine maturation. While most research has focused on adults, accumulating evidence indicates that these interactions are established early in life and influence pubertal timing, metabolic homeostasis, and neuroendocrine development. This review synthesizes current human evidence on microbiome-sex steroid relationships across childhood and adolescence, highlighting mechanistic insights and clinical implications for pediatric endocrinology.

RECENT FINDINGS: Gut microbes modulate steroid hormone metabolism through enzymatic deconjugation and enterohepatic circulation, while pubertal hormonal shifts reciprocally influence microbial diversity and function. Early-life dysbiosis linked to antibiotics, diet, or obesity may alter hypothalamic-pituitary-gonadal activity. Microbial metabolites such as short-chain fatty acids, bile acids, and tryptophan derivatives regulate immune, metabolic, and neuroendocrine pathways, affecting growth and insulin sensitivity. Disruptions of this microbiome-hormone axis are implicated in pubertal timing disorders, metabolic dysfunction, polycystic ovary syndrome (PCOS), and inflammatory intestinal diseases, whereas fiber-rich diets and probiotics may help restore balance.

SUMMARY: The microbiome-sex steroid axis constitutes a fundamental component of pediatric endocrine development. Understanding this bidirectional relationship provides a framework for microbiome-informed strategies aimed at preventing and managing pubertal, metabolic, and neuroendocrine disorders during childhood and adolescence.

PMID:41312613 | DOI:10.1097/MOP.0000000000001527

Assessment of Microplastic Exposure in Diabetic Patients Using Insulin - November 27, 2025

Toxics. 2025 Oct 29;13(11):926. doi: 10.3390/toxics13110926.

ABSTRACT

This study investigates the potential role of microplastics in the development of diabetes mellitus and assesses their presence in individuals undergoing insulin therapy. A total of 100 participants were included: 50 insulin-dependent diabetic patients and 50 healthy controls. The diabetic group was divided into two subgroups based on their insulin regimen: those receiving one daily injection of basal insulin and those receiving four injections of basal and short-acting insulin. Blood samples were analysed for microplastic content using chromatographic methods (LC/GC-MSMS and LCTOF MS). The findings revealed that diabetic patients had significantly higher serum microplastic levels (3.14 ± 1.30 µg/mL) than healthy individuals (1.50 ± 0.89 µg/mL, p < 0.05). Within the diabetic group, patients receiving four injections had a longer disease duration (15.14 ± 3.64 years) than those receiving one injection (10.56 ± 5.21 years), with a statistically significant difference (p = 0.001). However, microplastic levels did not differ significantly based on injection frequency. A strong positive correlation was observed between microplastic levels and both HbA1c (%) and fasting glucose levels (p = 0.001). These results imply that microplastics may act as endocrine disruptors that contribute to the development of diabetes, rather than being introduced through insulin treatment itself.

PMID:41304478 | PMC:PMC12656115 | DOI:10.3390/toxics13110926

Breastfeeding in a Polluted World: Perspective on the Properties of Breast Milk and the Need for Protection - November 27, 2025

J Clin Med. 2025 Nov 13;14(22):8034. doi: 10.3390/jcm14228034.

ABSTRACT

Breast milk (BM) is a unique biological fluid that represents the optimal nutritional source for infants, uniquely adapted through millions of years of evolution. BM is not only a nutritional fluid but a dynamic biological system, evolved to provide optimal growth, immune protection, and neurodevelopmental support. Its unique composition-including macronutrients, micronutrients, bioactive molecules, and stem cells-makes it essential in early life. Breastfeeding further promotes psychological well-being, secure attachment, and maternal-infant bonding. Yet, in recent decades, concern has grown over environmental contaminants in BM, including endocrine-disrupting chemicals (EDCs) and micro/nanoplastics. These pollutants have the potential to disrupt endocrine signaling, neurodevelopment, metabolic programming, and immune development, thereby undermining the natural advantages of breastfeeding. Therefore, a better understanding of the unique features of BM, while investigating the effects of these contaminants, is important for safeguarding maternal and infant health. This perspective article highlights the current knowledge on BM and indicates the need for further research. It also emphasizes the need for appropriate public health measures aimed at reducing exposure to pollutants and lowering associated risks, as well as preventive strategies to protect breast milk and breastfeeding in such a changing environment, as it is uniquely designed to promote the health of children.

PMID:41303070 | PMC:PMC12653506 | DOI:10.3390/jcm14228034

Network Toxicology and Molecular Docking Reveal the Toxicological Mechanisms of DEHP in Bone Diseases - November 27, 2025

Int J Mol Sci. 2025 Nov 10;26(22):10895. doi: 10.3390/ijms262210895.

ABSTRACT

Di(2-ethylhexyl) phthalate (DEHP), a widely employed exogenous plasticizer, has become pervasive in the environment and living organisms due to its extensive use in food packaging, medical devices, and daily consumer products, and is established as a typical endocrine-disrupting chemical. Growing evidence indicates a strong association between DEHP exposure and the incidence of chronic bone disorders, including osteoporosis (OP), osteoarthritis (OA), and osteonecrosis of the femoral head (ONFH). However, the molecular mechanisms underlying its pathogenic effects across these diseases remain poorly defined. In this study, we applied an environmental network toxicology approach to integrate predicted protein targets of DEHP with known disease-associated targets of the three bone disorders using multiple databases. Through Venn analysis, protein-protein interaction (PPI) network construction, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, we identified core targets and key signaling pathways. Molecular docking and molecular dynamics (MD) simulations were further employed to validate the binding modes and stability between DEHP and the core targets, thereby elucidating common and distinct mechanisms of DEHP across these bone diseases. A total of 109 overlapping targets of DEHP and the three bone diseases were identified, among which 7 core targets-AKT1, SRC, ESR1, CASP3, MMP9, BCL2, and BCL2L1-were common to all three disorders. These are implicated in critical biological processes such as apoptosis regulation, inflammation, extracellular matrix degradation, and estrogen signaling. KEGG enrichment analysis revealed significant involvement of the PI3K-Akt, MAPK, Ras, TNF, and estrogen signaling pathways across all three diseases. Molecular docking and MD simulations confirmed stable binding of DEHP to key targets including AKT1, ESR1, and MMP9, supporting its potential to disrupt bone metabolic homeostasis via multi-target and multi-pathway mechanisms. Further analysis indicated that DEHP exerts both shared and disease-specific effects: it disrupts osteoblast/osteoclast balance in OP, amplifies inflammatory responses and matrix degradation in OA, and contributes to impaired angiogenesis and osteocyte necrosis in ONFH. This study systematically reveals how DEHP disrupts bone homeostasis through a multi-target and multi-pathway network, constructing a cross-disease osteotoxicity framework. It is the first to delineate the common and distinct molecular mechanisms of DEHP in OP, OA, and ONFH. Although these insights are derived from computational models and require further experimental validation, they provide a novel theoretical basis for combined intervention strategies targeting multiple bone diseases and for environmental health risk assessment.

PMID:41303381 | PMC:PMC12652970 | DOI:10.3390/ijms262210895

Toxicological Impacts and Mechanistic Insights of Bisphenol a on Clear Cell Renal Cell Carcinoma Progression: A Network Toxicology, Machine Learning and Molecular Docking Study - November 27, 2025

Biomedicines. 2025 Nov 13;13(11):2778. doi: 10.3390/biomedicines13112778.

ABSTRACT

Background: Clear cell renal cell carcinoma (ccRCC) is a prevalent urological malignancy, accounting for approximately 1.6% of all cancer-related deaths in 2022. While endocrine-disrupting chemicals (EDCs) have been implicated as risk factors for ccRCC, the toxicological profiles and immune mechanisms underlying Bisphenol A (BPA) exposure in ccRCC progression remain inadequately understood. Materials and Methods: Protein-protein interaction (PPI) analysis and visualization were performed on overlapping genes between ccRCC and BPA exposure. This was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to elucidate potential underlying mechanisms. Subsequently, 108 distinct machine learning algorithm combinations were evaluated to identify the optimal predictive model. An integrated CoxBoost and Ridge regression model was constructed to develop a prognostic signature, the performance of which was rigorously validated across two independent external datasets. Finally, molecular docking analyses were employed to investigate interactions between key genes and BPA. Results: A total of 114 overlapping targets associated with both ccRCC and BPA were identified. GO and KEGG analyses revealed enrichment in cancer-related pathways, including pathways in cancer, endocrine resistance, PD-L1 expression and PD-1 checkpoint signaling, T-cell receptor signaling, endocrine function, and immune responses. Machine learning algorithm selection identified the combined CoxBoost-Ridge approach as the optimal predictive model (achieving a training set concordance index (C-index) of 0.77). This model identified eight key genes (CHRM3, GABBR1, CCR4, KCNN4, PRKCE, CYP2C9, HPGD, FASN), which were the top-ranked by coefficient magnitude in the prognostic model. The prognostic signature demonstrated robust predictive performance in two independent external validation cohorts (C-index = 0.74 in cBioPortal; C-index = 0.81 in E-MTAB-1980). Furthermore, molecular docking analyses predicted strong binding affinities between BPA and these key targets (Vina scores all <-6.5 kcal/mol), suggesting a potential mechanism through which BPA may modulate their activity to promote renal carcinogenesis. Collectively, These findings suggested potential molecular mechanisms that may underpin BPA-induced ccRCC progression, generating hypotheses for future experimental validation. Conclusions: These findings enhance our understanding of the molecular mechanisms by which BPA induces ccRCC and highlight potential targets for therapeutic intervention, particularly in endocrine and immune-related pathways. This underscores the need for collaborative efforts to mitigate the impact of environmental toxins like BPA on public health.

PMID:41301871 | PMC:PMC12650149 | DOI:10.3390/biomedicines13112778

Pfaffia glomerata Ameliorates BPA-Induced Reproductive Impairments in Mice by Suppressing Apoptosis via PI3K/AKT Signaling Activation - November 27, 2025

Pharmaceuticals (Basel). 2025 Oct 25;18(11):1614. doi: 10.3390/ph18111614.

ABSTRACT

Objectives: Bisphenol A (BPA), a prototypical environmental endocrine-disrupting chemical (EDC), is ubiquitously present in environmental matrices and biological fluids. Dietary ingestion and inhalation exposure to BPA can induce testicular oxidative stress and apoptosis. This study aimed to investigate the protective effects and underlying mechanisms of Pfaffia glomerata (Pg), a perennial herb of the Amaranthaceae family, against BPA-induced reproductive system injury. Methods: Potential targets and molecular mechanisms were predicted through network pharmacology. Physiological indicators, histopathological changes, serum biochemical parameters, and Western blot analysis were used to systematically evaluate the ameliorative effects of Pg and elucidate its mechanisms. Results: Our network pharmacology analysis identified core targets of Pg in attenuating reproductive system injury, including PTPN11, PIK3CA, JAK2, PIK3R1, PDGFRB, and others. GO enrichment and KEGG pathway analysis indicated that these key targets primarily regulate steroid metabolism, enhance antioxidant capacity, and modulate signaling pathways such as PI3K-AKT, Fc epsilon RI, and cAMP. In vivo studies demonstrated that all Pg dose groups showed significant improvement in BPA-induced histopathological injury to testicular tissues. BPA exposure increased serum levels of follicle-stimulating hormone (FSH) while decreasing testosterone (T), estradiol (E2), and progesterone (PROG) levels. Furthermore, BPA elevated serum levels of the testicular marker enzymes acid phosphatase (ACP) and lactate dehydrogenase (LDH) but reduced alkaline phosphatase (ALP) levels; all these effects were significantly reversed with Pg treatment. Western blot results showed that compared with the model group, high-dose Pg significantly upregulated the expression of phosphorylated AKT (p-AKT), phosphorylated PI3K (p-PI3K), and Bcl-2, while downregulating Cleaved Caspase-3 and Bax. Conclusions: Our findings indicate that Pg may attenuate BPA-induced reproductive system injury by activating the PI3K/AKT signaling pathway, upregulating the anti-apoptotic protein Bcl-2, and inhibiting the activation of the apoptotic effector Caspase-3. The study provides a new theoretical basis for the development of novel natural drugs or health products.

PMID:41304861 | PMC:PMC12655148 | DOI:10.3390/ph18111614

Polycystic Ovary Syndrome (PCOS)-Specific Risk Appraisal of the Sunscreen Ultraviolet (UV) Filters (Oxybenzone/Octinoxate) - November 27, 2025

Toxics. 2025 Oct 29;13(11):927. doi: 10.3390/toxics13110927.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder affecting 6-20% of women of reproductive age, manifesting through hyperandrogenism, ovulatory dysfunction, insulin resistance, and diverse metabolic derangements. Increasing evidence highlights the contribution of environmental factors, particularly endocrine-disrupting chemicals (EDCs), to PCOS susceptibility and severity. Sunscreen ultraviolet (UV) filters such as oxybenzone (benzophenone-3) and octinoxate (ethylhexyl methoxycinnamate) are widely used EDCs with established systemic absorption and biomonitoring evidence in human populations. Their endocrine-disrupting potential encompasses estrogenic and anti-androgenic activity, interference with steroidogenic enzymes, modulation of thyroid hormone, induction of oxidative stress, and epigenetic reprogramming, all of which are mechanistic pathways that overlap with PCOS pathophysiology. This evidence-based study critically appraises the evidence linking oxybenzone and octinoxate exposures to ovarian endocrinology, with a PCOS-specific focus. Human exposure patterns, pharmacokinetics, and regulatory perspectives are summarized alongside preclinical and in vitro data implicating these filters in ovarian dysfunction. Mechanistic intersections with PCOS include hyperandrogenism, disrupted folliculogenesis, oxidative stress-adipokine imbalance, and potential impairment of vitamin D signaling. Although epidemiological studies directly addressing PCOS outcomes remain sparse, the convergence of toxicological evidence with known endocrine vulnerabilities in PCOS underscores a need for targeted investigation. By mapping exposure pathways and mechanistic disruptions, this appraisal emphasizes the translational relevance of UV filter toxicity in the context of PCOS. It advocates for PCOS-specific biomonitoring cohorts, mechanistic studies, and regulatory consideration of reproductive endpoints while balancing the dermatological benefits of photoprotection against reproductive risks.

PMID:41304479 | PMC:PMC12656294 | DOI:10.3390/toxics13110927

Sonochemically assisted synthesis of geothermal silica scaling-derived mesoporous silica as a green adsorbent for bisphenol A - November 27, 2025

Environ Sci Pollut Res Int. 2025 Nov 27. doi: 10.1007/s11356-025-37192-8. Online ahead of print.

ABSTRACT

The increase in production in the chemical manufacturing industry has led to high levels of waste generated as a byproduct. Inadequate waste management has resulted in water pollution by micropollutants, such as bisphenol A (BPA). BPA, as an endocrine-disrupting compound, has various negative effects on human health and aquatic environments. BPA adsorption using mesoporous silica (MS) can be an economic and efficient solution to overcome this problem. However, MS is typically synthesized using tetraethyl orthosilicate (TEOS), which is toxic and expensive. Therefore, this study explores the use of geothermal silica scaling as an environmentally friendly source of silica for MS synthesis. The sol-gel process was modified using a sonochemical approach, and the effect of the sonication time on MS characteristics was analyzed. The results showed that increasing the sonication time affected the growth of the regular meso-sized pore structure, with a sonication time of 30 min (MS-US 30) producing MS with optimal pore and surface properties. MS-US 30 has a hexagonal structure, with a specific surface area of 181 m² g^-1, pore size of 3.79 nm, and pore volume of 0.18 cm³ g^-1. MS-US 30 showed promising adsorption performance against BPA, with a removal efficiency and adsorption capacity of up to 64.94% and 194.81 mg g^-1, respectively, within a contact time of 3 h at a pH of 10. The synthesis of MS from geothermal silica scaling provides a sustainable approach to MS synthesis, showing reliable adsorption performance and potential for further development. These findings also suggest that sonication-assisted synthesis offers a more efficient and favorable alternative route for MS synthesis.

PMID:41307810 | DOI:10.1007/s11356-025-37192-8

Heartfulness meditation alters neuroendocrine profiles: A randomized controlled trial on hormones of stress and well-being - November 27, 2025

Medicine (Baltimore). 2025 Nov 21;104(47):e45559. doi: 10.1097/MD.0000000000045559.

ABSTRACT

BACKGROUND: Chronic stress disrupts the neuroendocrine system, leading to imbalances in neurotransmitters and stress hormones such as oxytocin, β endorphins and cortisol, contributing to mood disorders and poor emotional regulation. Complementary and alternative practices like meditation have shown promising results in stress regulation and mood elevation. Heartfulness (HFN) meditation, rooted in yogic traditions and incorporating yogic transmission, is an emerging technique to improve emotional resilience and hormonal homeostasis. Therefore, this study aimed to evaluate the effects of HFN meditation on oxytocin, β-endorphins, and cortisol. It also evaluated the changes in meditation depth using validated psychometric tools.

METHODS: A randomized controlled trial was conducted. Participants were divided into experimental and control groups. The experimental group practiced guided HFN meditation for 30 days. Following this, a crossover design was implemented in which, the control group participants were now given the intervention of HFN meditation. Biochemical markers (serum oxytocin, β-endorphins, cortisol) were measured at day 30, and day 60. Psychometric assessments included the Meditation Depth Questionnaire and the Positive and Negative Affect Schedule (PANAS).

RESULTS: HFN meditation significantly improved meditation depth (ΔM = -14.87, 95% CI [-23.61,-6.13], P = .001, r = 0.333) and positive affect (ΔM = -8.48, 95% CI [-12.03,-4.93], P < .001, r = 0.29), while reducing negative affect (ΔM = 7.70, 95% CI [3.81, 11.60], P < .001, r = 0.21). Oxytocin and endorphin levels increased (oxytocin ΔM = +88.18, P = .003, r = 0.355 and endorphin ΔM = +94.83, P = .003, r = 0.357), and cortisol decreased (ΔM = -133.55, P < .001, r = 0.661). After crossover, the control group exhibited similar improvements. Negative correlations were found between cortisol and both oxytocin and β-endorphins.

CONCLUSION: HFN meditation significantly modulates stress-related neuroendocrine markers and enhances positive emotional states. By increasing the levels of these happy hormones and reducing cortisol, HFN presents a promising non-pharmacological intervention for improving mental health and stress resilience.

PMID:41305815 | PMC:PMC12643779 | DOI:10.1097/MD.0000000000045559

Mono-(2-ethylhexyl) phthalate impairs insulin secretion in rat insulinoma cells by inducing ferroptosis via oxidative stress - November 27, 2025

Ecotoxicol Environ Saf. 2025 Nov 26;307:119459. doi: 10.1016/j.ecoenv.2025.119459. Online ahead of print.

ABSTRACT

Di(2-ethylhexyl) phthalate (DEHP), a frequently used plasticizer, is a prototypical endocrine-disrupting chemical. The mechanism by which DEHP affects glucose regulation and insulin resistance has not been fully elucidated. Mono-(2-ethylhexyl) phthalate (MEHP) is the principal DEHP metabolite. In this study, rat insulinoma (INS-1) cells were treated with MEHP at 30, 60, and 120 μM for 24 h. Compared to the 0 μM MEHP (control group), 30, 60, and 120 μM MEHP significantly lowered insulin secretion and raised intracellular Fe²⁺ levels in INS-1 cells, while reducing SOD and GSH levels and increasing ROS levels (all P < 0.05). MDA levels increased in the 60 and 120 μM MEHP groups (all P < 0.05). MEHP exposure disrupted iron metabolism and ferroptosis pathways, upregulating TFR1 mRNA and protein, downregulating FTH1 mRNA and protein, and increasing STEAP3 mRNA and protein expression. SLC7A11 and GPX4 mRNA and protein expression were significantly suppressed (all P < 0.05). Fer-1 (1 μM) effectively alleviated MEHP-induced cytotoxicity, restored GSIS capacity, reduced intracellular Fe²⁺ accumulation, ameliorated oxidative damage, and reactivated the SLC7A11/GPX4 signaling pathway in INS-1 cells (all P < 0.05). This study demonstrates that MEHP induces Fe²⁺ accumulation, oxidative stress, lipid peroxidation, and ferroptosis in INS-1 cells via the suppression of the SLC7A11/GPX4 signaling pathway, consequently impairing IS. Fer-1 alleviated these effects. These findings establish ferroptosis as a novel mechanism underlying DEHP/MEHP-induced β cell dysfunction and provide new insights into the role of PAEs, environmental pollutants, in diabetes pathogenesis.

PMID:41308353 | DOI:10.1016/j.ecoenv.2025.119459

EndoCompass Project: Environmental Endocrinology - November 27, 2025

Horm Res Paediatr. 2025 Nov 27:1-24. doi: 10.1159/000549151. Online ahead of print.

ABSTRACT

BACKGROUND: Endocrine science remains underrepresented in European Union research programmes despite the fundamental role of hormone health in human well-being. Analysis of the CORDIS database reveals a persistent gap between the societal impact of endocrine disorders and their research prioritization. At national funding level, endocrine societies report limited or little attention of national research funding towards endocrinology. The EndoCompass project - a joint initiative between the European Society of Endocrinology and the European Society of Paediatric Endocrinology, aimed to identify and promote strategic research priorities in endocrine science to address critical hormone-related health challenges.

METHODS: Research priorities were established through a comprehensive analysis of the EU CORDIS database covering the Horizon 2020 framework period (2014-2020). An expert analysis was conducted by leading researchers in environmental endocrinology, integrating literature review, epidemiological evidence, and emerging research priorities to identify key challenges and opportunities across endocrine systems.

RESULTS: Research priorities span 5 critical domains: mechanisms and biomarkers of endocrine-disrupting chemical (EDC) actions; environmental pharmaceutical contamination; climate change effects on endocrine function; endocrine consequences of air and water pollution; and mechanisms linking environmental stress to hormone disruption. Special emphasis is placed on understanding developmental programming, transgenerational effects, and implications for public health policy.

CONCLUSIONS: This component of the EndoCompass project provides an evidence-based roadmap for strategic research investment. The analysis demonstrates that environmental factors like EDCs fundamentally impact multiple endocrine systems, requiring coordinated research approaches. The findings support the broader EndoCompass objective of aligning research funding with areas of highest potential impact in endocrine health.

PMID:41308060 | DOI:10.1159/000549151

Simulated sunlight-driven activation of Ferrate(VI) with BiOBr for accelerated oxidation of bisphenol S (BPS) - November 27, 2025

J Hazard Mater. 2025 Nov 22;500:140568. doi: 10.1016/j.jhazmat.2025.140568. Online ahead of print.

ABSTRACT

Bisphenol S (BPS), a prevalent substitute for Bisphenol A, is a concerning endocrine-disrupting chemical frequently detected in the environment. This study constructs a novel synergistic system coupling BiOBr photocatalyst with Ferrate(VI) [Fe(VI)] under simulated sunlight (Xe lamp) for rapid BPS degradation. The system achieved 93.9 % removal of 10 μM BPS within 5 min at pH 8.0, with an apparent second-order rate constant of 459.10 M^-1 s^-1, approximately 80 times higher than that of the Fe(VI)-single/Dark system. Mechanistic investigation by electron spin resonance and quenching experiments identified singlet oxygen (¹O₂) as the primary reactive species responsible for the enhancement. Acting synergistically, BiOBr promoted Fe(VI) decomposition to boost ¹O₂ generation while facilitating electron transfer from BPS to oxidants, as verified by electrochemical and spectroscopic analyses. Eight transformation products were identified, unveiling degradation pathways involving hydroxylation, polymerization, carboxylation, and bond cleavage. The system exhibited excellent environmental compatibility, showing strong anti-interference ability against common water constituents, high degradation efficiency in real river water, and outstanding catalyst reusability with minimal bismuth leaching (0.062 mg/L). Moreover, toxicity assessment indicated an overall detoxification effect. This work provides a practical and sustainable strategy for water purification using the synergistic BiOBr-Fe(VI) system.

PMID:41308457 | DOI:10.1016/j.jhazmat.2025.140568

Temporal changes in amino acid profiles coordinate mosquito physiology and egg maturation in Aedes aegypti - November 27, 2025

BMC Biol. 2025 Nov 27;23(1):346. doi: 10.1186/s12915-025-02460-z.

ABSTRACT

BACKGROUND: Female Aedes aegypti mosquitoes utilize host blood to support egg maturation by digesting, absorbing, and metabolizing its components. Among these, amino acids are essential as both signaling molecules and building blocks for yolk proteins. While their overall importance is established, the individual dynamics and regulation of each amino acid remain insufficiently understood.

RESULTS: We systematically profiled free and protein-bound amino acids in whole bodies, ovaries, and excreta over time after blood feeding, revealing distinct temporal dynamics across amino acids. Notably, tyrosine, enriched in yolk proteins, exhibited a biphasic pattern: a transient decrease between 6 and 9 h post blood meal, followed by accumulation during egg maturation. We also performed RNA-seq and found that amino acid metabolism is partially regulated by 20-hydroxyecdysone (20E), indicating hormonal control of amino acid homeostasis. Integrating RNA-seq analysis with amino acid profiling further suggested an adaptation to metabolic imbalance between host blood and ovaries. The early decrease in tyrosine was attributed to enzymatic degradation by 4-hydroxyphenylpyruvate dioxygenase (Hpd), whose expression is induced by 20E, a key hormone orchestrating post-blood-feeding gene expression and egg maturation. Pharmacological inhibition of Hpd caused tyrosine accumulation and increased lethality, indicating that tight regulation of tyrosine catabolism is essential for survival.

CONCLUSIONS: This study highlights the temporally coordinated metabolism of individual amino acids during mosquito reproduction. Our dataset serves as a valuable resource for understanding nutrient allocation with endocrine regulation, as well as a foundation for developing novel strategies to disrupt mosquito survival by targeting the metabolic enzymes.

PMID:41299610 | PMC:PMC12659091 | DOI:10.1186/s12915-025-02460-z

Acute Exposure to a Common Organic UV Filter Does Not Alter the mRNA of Gonadal Estrogen or Growth Hormone Receptors in Mozambique Tilapia (Oreochromis mossambicus) In Vitro - November 27, 2025

Genes (Basel). 2025 Nov 10;16(11):1357. doi: 10.3390/genes16111357.

ABSTRACT

BACKGROUND/OBJECTIVES: Organic UV filters are chemical compounds that are commonly used in sunscreen products to absorb UV radiation from the Sun. To date, the filters have been detected in aquatic environments worldwide, as well as in aquatic organisms, including fish and coral. Hydroxy-4-methoxybenzophenone (BP-3) is a common organic UV filter and it is well documented to be among the filters that are detectable worldwide in water samples and aquatic organisms. Long-term exposure in vivo studies have demonstrated that high doses of BP-3 can cause endocrine-disrupting effects in aquatic organisms.

METHODS: Using gonadal cell culture and quantitative RT-PCR, our study aimed to ascertain the effect of environmentally relevant doses of BP-3 (detected in aquatic systems) on the gene expression of reproductive targets, estrogen and growth hormone receptors (ERs and GHRs), in Mozambique tilapia (Oreochromis mossambicus) after an acute 24 h treatment.

RESULTS/CONCLUSIONS: Our study is the first to use an in vitro design to investigate the mechanism of the action of BP-3 on gonadal tissue in fish. Our results show that BP-3 does not induce gene regulation directly on the gonads of tilapia at doses that are comparable to what is detectable in aquatic environments after 24 h. We do verify, as seen in other teleost species, homologous regulation of ERβ in male tilapia gonadal tissue.

PMID:41300808 | PMC:PMC12652211 | DOI:10.3390/genes16111357

Crossing silos: how changes in EU chemicals policy and legislation are reflected in its pharmaceutical policy and legislation - November 27, 2025

J Pharm Policy Pract. 2025 Nov 24;18(1):2587439. doi: 10.1080/20523211.2025.2587439. eCollection 2025.

ABSTRACT

BACKGROUND: The European Union (EU) has introduced several changes to its chemicals policy and legislation with an ambition to transform society greener. This study examined selected changes introduced in EU chemicals policy and legislation and how they may affect the pharmaceutical sector. The objective was to find out whether structural changes in one political sphere (chemicals) influence the other political sphere (health).

METHODS: First, concrete changes to EU chemicals legislation or its implementation were identified. Then, qualitative content analysis was used to analyse how these changes are reflected in EU pharmaceutical policy, legislation and related guidance documents. Data was analysed using both deductive and inductive approaches. The concrete changes identified were used as codes for the deductive classification of quotations. The analysis continued inductively by examining these quotations for the topics they raise in EU pharmaceutical policy, legislation and related guidance.

RESULTS: The results imply that structural changes in EU political sphere of chemicals may have a range of implications for the pharmaceutical sector. The need for derogations in certain cases regarding medicinal products was recognised, but in general, the pharmaceutical sector will not be exempted from the application of the new provisions. However, changes to EU chemicals legislation were rarely referred to in pharmaceutical policy, legislation and guidance. An inductive analysis of the quotations revealed that some changes (such as substances with endocrine-disrupting properties and changes to EU water legislation) have got more prominence in the pharmaceutical sector than others.

CONCLUSION: The analysis indicated that the pharmaceutical sector is taking a defensive approach to changes in EU chemicals legislation. This may be partly because many changes occur simultaneously, creating uncertainty about their combined and cumulative impacts. Closer cooperation between the Environment and Health Directorates-General is needed to steer more coherent transformation governance across different policy sectors in the EU.

PMID:41306736 | PMC:PMC12646081 | DOI:10.1080/20523211.2025.2587439

Endocrine-disrupting chemicals in cosmetics: mechanistic insights and their impact on human and skin health - November 27, 2025

Rev Endocr Metab Disord. 2025 Nov 27. doi: 10.1007/s11154-025-10006-5. Online ahead of print.

ABSTRACT

The increasing use of cosmetics and therapeutic products has raised concerns about their effects on skin health and overall well-being. This review focuses on the toxicological impact of cosmetic ingredients, particularly endocrine-disrupting chemicals (EDCs) such as benzophenones, triclosan, phthalates, and parabens. Frequently present in skincare, haircare, and cosmetic products, these compounds have been associated with adverse outcomes, including carcinogenesis, skin disorders, hormonal imbalances, and reproductive health issues. Despite extensive research on parabens, phthalates, triclosan, and benzophenones, significant uncertainties persist, underscoring the need for further investigation to understand previous findings better. To mitigate these risks, the review recommends adopting safer alternatives, increasing consumer awareness, and enforcing stricter regulatory measures. This comprehensive analysis aims to bridge existing knowledge gaps, empower consumers to make informed choices, and advocate for strict safety standards in personal care products to safeguard skin health and support long-term well-being.

PMID:41307807 | DOI:10.1007/s11154-025-10006-5

Advances in understanding the role of inflammatory factors and immune cells in the pathology of epilepsy, mediated by neuroimmune interactions within the gut-brain axis - November 27, 2025

Front Cell Dev Biol. 2025 Nov 11;13:1650909. doi: 10.3389/fcell.2025.1650909. eCollection 2025.

ABSTRACT

Epilepsy is a prevalent chronic neurological disorder, affecting approximately 70 million individuals globally, with its pathogenesis primarily attributed to recurrent seizures caused by abnormal neuronal discharges in the brain. Recent research has increasingly recognized the critical role of neuroinflammation in the central nervous system in the onset and progression of epilepsy. Furthermore, the gut-brain axis, a crucial link between gut microbiota and the central nervous system, facilitates communication through intricate pathways involving neural, immune, and endocrine mechanisms, and its involvement in epilepsy pathology is gaining significant attention. This review focuses on recent advances in neuroimmune interactions within the gut-brain axis in epilepsy. It explores the roles of inflammatory factors (e.g., IL-1β, IL-6, TNF-α) and immune cells (e.g., microglia, macrophages, neutrophils) in epileptic pathophysiology, and systematically reviews relevant experimental and clinical studies. The article begins by providing an overview of the fundamental interactions between gut microbiota and the host immune system, before discussing how gut-derived immune signals influence the central nervous system via the gut-brain axis. The pathogenic mechanisms of key pro-inflammatory factors in epileptogenesis are then examined, including how IL-1β promotes neuronal hyperexcitability, how IL-6 mediates neuroinflammation, and how TNF-α disrupts the balance between neuronal excitation and inhibition. Additionally, the article highlights the significant role of inflammatory cells in the central nervous system, particularly the activation of microglia and the infiltration of peripheral immune cells in epilepsy development. In conclusion, further investigation into the mechanisms of neuroimmune interactions in the gut-brain axis may lead to the identification of novel biomarkers and therapeutic targets for epileptogenesis, offering new insights and directions for the treatment of refractory epilepsy.

PMID:41306289 | PMC:PMC12644102 | DOI:10.3389/fcell.2025.1650909

Subclinical Myocardial Dysfunction in Pituitary Neuroendocrine Tumor Patients: A 2D Speckle-Tracking Echocardiography Study - November 27, 2025

Endocr Connect. 2025 Nov 27:EC-25-0641. doi: 10.1530/EC-25-0641. Online ahead of print.

ABSTRACT

Pituitary neuroendocrine tumors (PitNETs) cause hormonal hypersecretion, which can disrupt cardiovascular homeostasis and lead to both overt and subclinical cardiac dysfunction. This study retrospectively examined 198 hospitalized PitNET patients (n=91 male, n=107 female) from March 2019 to December 2022. Two-dimensional speckle-tracking echocardiography (2D-STE) was used to determine the absolute left ventricular global longitudinal strain (GLS) values. Comprehensive clinical information was gathered, including endocrine axis status, symptoms, surgery history, and demographics. Standard transthoracic echocardiography parameters were also recorded. Multiple linear regression analysis and intergroup comparisons were used to identify factors affecting GLS. Pre-planned subgroup analyses were conducted for the acromegaly cohort and by surgical status. Clinical presentations overlapped across tumor subtypes. Cranial imaging was the primary method for detecting cases with atypical symptoms. Female patients were older and sought treatment more frequently than males. The mean patient age was 43.7 years, with most diagnoses occurring between 30 and 50 years. GLS showed a significant positive correlation with EF (62.64±5.04%; p=0.00) and E/e' ratio (7.10±1.96; p=0.01), and a significant negative correlation with BMI (25.20±3.92 kg/m2; p=0.00). Significant differences in GLS were observed based on gender (t=2.47, p=0.01) and operator (t=2.52, p=0.01). Regression analysis identified baseline predictors (BMI), EF, LV function, and gender as independent predictors of GLS. A key finding from a dedicated acromegaly subgroup analysis was that disease activity (IGF-1) independently predicted impaired GLS. 2D-STE is a sensitive tool for detecting subclinical myocardial dysfunction in PitNET patients. GLS is significantly influenced by BMI, EF, left ventricular dimensions, and gender, underscoring the need to integrate metabolic and cardiac profiles into the cardiovascular assessment of this population. Furthermore, the identification of IGF-1 as a predictor in acromegaly highlights the value of disease-specific cardiac risk stratification.

PMID:41307388 | DOI:10.1530/EC-25-0641

Bisphenol A Alters the Expression of Genes Involved in Lipogenesis, Inflammation, and Oxidative Stress in the Liver of Adult Zebrafish - November 27, 2025

Pharmaceuticals (Basel). 2025 Nov 20;18(11):1765. doi: 10.3390/ph18111765.

ABSTRACT

Background: Bisphenol A (BPA) is a widespread environmental endocrine disruptor associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, its short-term effects at low, environmentally relevant concentrations are still poorly understood. Methods: Adult zebrafish were exposed to 5, 20, or 100 µg/L BPA for 48 h, 7, or 14 days in a pilot test. The lowest effective condition (20 µg/L for 7 days) was selected for a complete experiment. Fish were divided into two groups: control and BPA-exposed (n = 50/group). After exposure, livers were collected for histological (HE, Oil Red O, Nile Red) and molecular (RT-qPCR) analyses. Results: Exposure to 20 µg/L BPA for 7 days induced moderate to severe hepatic steatosis, characterized by vacuolization, hepatocyte ballooning, and lipid accumulation. Gene expression analysis showed upregulation of fasn (fatty acid synthase), acc1 (acetyl-CoA carboxylase 1), srebp-1c (sterol regulatory element-binding protein 1c), nfkb (nuclear factor kappa B), il-6 (interleukin-6), gpx1 (glutathione peroxidase 1), sod (superoxide dismutase), cyp1a (cytochrome P450 1A), and cyp2ad2 (cytochrome P450 2AD2), while adipor2 (adiponectin receptor 2) and gpx4 (glutathione peroxidase 4) were downregulated (decreased activity). Conclusions: Short-term exposure to a low, environmentally relevant concentration of BPA was sufficient to trigger hepatic steatosis in zebrafish. These effects were associated with enhanced lipogenesis, inflammation, oxidative imbalance, and altered xenobiotic metabolism, suggesting that even brief, low-dose BPA exposure may contribute to early events in MASLD pathogenesis.

PMID:41305006 | PMC:PMC12655367 | DOI:10.3390/ph18111765

Reduced Pineal Gland Volume in Oncology Patients: Association with Chemotherapy Duration - November 27, 2025

Medicina (Kaunas). 2025 Oct 27;61(11):1923. doi: 10.3390/medicina61111923.

ABSTRACT

Background and Objectives: The pineal gland is a neuroendocrine structure whose function can be disrupted in patients with malignancies. This study examines the differences in pineal gland volume between oncology patients and healthy controls, as well as the relationship between volume and the duration of chemotherapy. Materials and Methods: A retrospective study included 400 participants, divided into two groups: 200 oncology patients and 200 healthy controls. The pineal gland volume was measured using MRI scans, utilizing T1-sagittal, T2-coronal/axial sections, and post-contrast 3D T1W MPRAGE tomograms. The volume was calculated based on the ellipse approximation formula: V = (L × H × W)/2. The study analyzed the relationships between pineal gland volume and factors such as age, sex, primary tumor origin, and the duration of chemotherapy. Results: The pineal gland volume was significantly smaller in oncology patients in comparison with the healthy controls (p < 0.001). The average volume in oncology patients was 32.41 ± 16.79 mm³, whereas in healthy controls, it was 59.26 ± 29.99 mm³. A significantly smaller pineal gland volume was observed in patients with malignancies, regardless of sex, with no notable differences between groups. Age also did not significantly influence gland volume (p > 0.05). The primary tumor site did not significantly influence gland volume (p > 0.05). A moderate positive correlation was observed between the duration of chemotherapy and pineal gland volume (ρ = 0.322; p = 0.007). Conclusions: The pineal gland showed reduced volume in oncology patients compared to controls. The observed positive correlation with chemotherapy duration should be interpreted cautiously and may reflect survivorship bias rather than direct treatment effects.

PMID:41303760 | PMC:PMC12654074 | DOI:10.3390/medicina61111923

Maternal Exposure to 2,4-Di-tert-butylphenol During Pregnancy in a Mouse Model Leads to Abnormal Development of the Urinary System in Offspring - November 27, 2025

Toxics. 2025 Nov 18;13(11):991. doi: 10.3390/toxics13110991.

ABSTRACT

The occurrence of congenital anomalies of the kidney and urinary tract (CAKUT) is influenced by intrauterine environmental factors, and maternal exposure to endocrine-disrupting chemicals (EDCs) during pregnancy may affect the kidney development of offspring. 2,4-Di-tert-butylphenol (2,4-DTBP) is a high-production volume chemical classified as an EDC, which has been detected in humans and has been found to increase mortality and malformation rates in zebrafish embryos. Its effects on mammalian development are still unknown. In this study, a maternal mouse model exposed to 2,4-DTBP throughout pregnancy was established by gavage. The overall conditions of the maternal mice and their offspring were observed, and the concentrations of 2,4-DTBP in maternal serum and offspring tissues were measured using liquid chromatography-tandem mass spectrometry. Exposure to 2,4-DTBP of 75 µg/g·day during pregnancy markedly reduced the early pregnancy rate in mice to 41.75% (95% CI: 33.53-49.97%; n = 139), compared to 82.29% (95% CI: 74.18-90.39%; n = 85) in the controls (p < 0.0001), with a relative risk (RR) of 0.51 (95% CI: 0.41-0.63). 2,4-DTBP could accumulate in maternal mice and be transferred to embryos and internal organs of the offspring, and is associated with the elevated risk of CAKUT in the offspring, primarily manifesting as hydronephrosis/ureteral dilation. The CAKUT rate of DTBP-75 group is 33.59% (95% CI: 17.62-49.56%; N = 9, n = 56), compared to 11.85% (95% CI: 2.43-21.28%; N = 9, n = 67) in the controls (p = 0.02), RR = 2.53 (95% CI: 1.18-5.42). These findings enhance the understanding of the health risks posed by 2,4-DTBP and provide a theoretical basis for environmental monitoring in public health.

PMID:41304543 | PMC:PMC12656196 | DOI:10.3390/toxics13110991

Preliminary Identification of PFAS and Other Emerging Contaminants in the French Broad River, NC Post-Hurricane Helene - November 27, 2025

Toxics. 2025 Oct 22;13(11):905. doi: 10.3390/toxics13110905.

ABSTRACT

Hurricanes are increasingly impacting inland water systems, yet their role in mobilizing anthropogenic contaminants remains insufficiently characterized. This study presents a preliminary assessment of organic contaminant loading in the French Broad River, North Carolina, 15 days after flooding from Hurricane Helene. Surface water samples from five sites were analyzed using liquid chromatography-high-resolution mass spectrometry. Targeted analysis quantified 11 per- and polyfluoroalkyl substances (PFASs), with summed concentrations ranging from 1.49 to 70.8 ng/L. One downstream site exhibited the highest burden, where PFOSs and PFOA exceeded U.S. EPA drinking water maximum contaminant levels. Non-targeted analysis (NTA) and suspect screening identified 468 compounds, with 96 structurally annotated at high confidence. Of these, a large proportion were associated with medium to high hazard potential, particularly for acute aquatic toxicity (69%), developmental toxicity (64%), mutagenic genotoxicity (49%), endocrine disruption (35%), skin irritation (27%), eye irritation (26%), and carcinogenicity (17%). Four EPA priority pollutants-4-nitrophenol, 2,4,6-trichlorophenol, pentachlorophenol, and dibutyl phthalate-were also detected. Site-specific chemical profiles suggested inputs from flood-damaged wastewater infrastructure and plastic debris. These findings highlight the susceptibility of freshwater systems to contaminant mobilization during extreme flooding and demonstrate the value of combining NTA and cheminformatics for post-disaster monitoring.

PMID:41304458 | PMC:PMC12656598 | DOI:10.3390/toxics13110905

Assessment of Microplastic Exposure in Diabetic Patients Using Insulin - November 27, 2025

Toxics. 2025 Oct 29;13(11):926. doi: 10.3390/toxics13110926.

ABSTRACT

PMID:41304478 | PMC:PMC12656115 | DOI:10.3390/toxics13110926

Crossing silos: how changes in EU chemicals policy and legislation are reflected in its pharmaceutical policy and legislation - November 27, 2025

J Pharm Policy Pract. 2025 Nov 24;18(1):2587439. doi: 10.1080/20523211.2025.2587439. eCollection 2025.

ABSTRACT

PMID:41306736 | PMC:PMC12646081 | DOI:10.1080/20523211.2025.2587439

Downregulation of Enteroendocrine Genes Predicts Survival in Colon Cancer: A Bioinformatics-Based Analysis - November 27, 2025

Int J Mol Sci. 2025 Nov 18;26(22):11127. doi: 10.3390/ijms262211127.

ABSTRACT

Colorectal cancer (CRC) is the fourth most common and the third mostly deadly cancer globally. Even with alternative therapies, some patients do not respond to treatment. Identifying modulations in the tumor microenvironment (TME) of CRC is a significant challenge due to the complex and dynamic nature of the TME. The intestinal epithelium comprises different types of secretory lineage cells, including goblet, tuft, Paneth, and enteroendocrine cells (EECs). Yet the relevance of each subtype of secretory intestinal epithelial cell (IEC) within the TME is still debated. This study investigated the involvement of IECs in CRC development through an integrative bioinformatics analysis. We used publicly available datasets from the National Center for Biotechnology Information, the Cancer Genome Atlas Program, and the National Cancer Institute's Proteomics Tumor Analysis Consortium, encompassing both human and mouse CRC samples. Our findings reveal a CRC microenvironment characterized by elevated expression levels of genes associated with WNT pathway activity. Remarkably, there was increased expression of Paneth cell-associated markers and transcription factors, such as WISP1, LYZ, SOX9, and DEFA1. Conversely, EEC-specific gene markers, such as GCG (encoding glucagon-like peptide-1) and CHGA exhibited significant downregulation in CRC tissue compared with healthy tissue, partially due to Paneth cell activity. Gene ontology analysis showed species-conserved downregulation in hormone/peptide secretion-related pathways in both mouse and human CRC. Of note, lower levels of GCG and CHGA correlated with reduced overall survival and demonstrated a correlation with the cell cycle, apoptosis, and proliferation. These results suggest that the disruption of enteroendocrine cell signaling is a hallmark of CRC development and may hold prognostic and therapeutic value in treating CRC patients.

PMID:41303610 | PMC:PMC12652218 | DOI:10.3390/ijms262211127

Transcriptomic Analysis of the Diamondback Moth Under Exposure to the Juvenile Hormone Esterase (JHE) Inhibitor 3-Octylthio-1,1,1-trifluoro-2-propanone (OTFP) - November 27, 2025

Insects. 2025 Nov 11;16(11):1152. doi: 10.3390/insects16111152.

ABSTRACT

Targeting juvenile hormone esterase (JHE) is an emerging strategy to combat the broadly resistant pest, Plutella xylostella; this study employed transcriptomics to investigate the sublethal effects of the JHE inhibitor OTFP, revealing a non-monotonic dose response characterized by stronger transcriptional changes at lower concentrations, resulting in low mortality, prolonged pupation time, and increased pupal weight. The results from the Differentially Expressed Genes (DEGs) analysis revealed that the core effect of OTFP is the persistent perturbation of the "insect hormone biosynthesis" pathway and altered expression of components of the JH/20E axis; to cope with this stress, the larvae exhibited a dual defense associated with compensatory upregulation of JH-degrading enzyme genes to attempt to restore hormone homeostasis, and the activation of a broad-spectrum detoxification network to clear the compound. More critically, the developmental delay resulting from endocrine disruption KEGG-enriched growth-related pathways (amino-acid and central-carbon metabolism; ribosome biogenesis; aminoacyl-tRNA biosynthesis), consistent with a growth-permissive milieu during prolonged feeding. This study therefore elucidates a novel integrative regulatory network that links endocrine disruption, detoxification, and compensatory growth, revealing a complex physiological trade-off strategy in this pest that sacrifices developmental tempo for survival.

PMID:41302898 | PMC:PMC12653607 | DOI:10.3390/insects16111152

Breastfeeding in a Polluted World: Perspective on the Properties of Breast Milk and the Need for Protection - November 27, 2025

J Clin Med. 2025 Nov 13;14(22):8034. doi: 10.3390/jcm14228034.

ABSTRACT

PMID:41303070 | PMC:PMC12653506 | DOI:10.3390/jcm14228034

Association between Endocrine Disruptors and Surgical Congenital Malformations: Systematic Review and Meta-Analysis - November 27, 2025

J Pediatr Surg. 2025 Nov 25:162829. doi: 10.1016/j.jpedsurg.2025.162829. Online ahead of print.

ABSTRACT

BACKGROUND: Prenatal exposure to endocrine disruptors (EDs) represents a growing public health concern due to its potential association with congenital malformations requiring pediatric surgical intervention. The ubiquity of these chemicals in modern environments and their ability to interfere with normal hormonal development during critical fetal windows raises significant concerns for pediatric surgeons. This systematic review was registered prospectively in PROSPERO (CRD420251158778).

METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, Embase, Web of Science, and gray literature from 2010-2025 for observational studies evaluating prenatal exposure to phthalates, bisphenols, perfluorinated compounds (PFAS), and organochlorines, with outcomes of surgical congenital malformations. Quality was assessed using the Newcastle-Ottawa Scale and GRADE methodology. Random-effects meta-analysis was performed using R software.

RESULTS: Of 4,121 studies identified, 66 met inclusion criteria (total population: 35,732). According to the Newcastle-Ottawa Scale, 42 studies (64%) had high quality (≥7 points), 18 (27%) moderate quality (5-6 points), and 6 (9%) low quality (<5 points). Significant associations were found between ED exposure and hypospadias (pooled OR: 2.21, 95% CI: 1.15-3.27; I²=65.4%, p=0.003), cryptorchidism (OR: 1.85, 95% CI: 1.02-3.36; I²=58.2%, p=0.041), and congenital heart disease (OR: 1.39, 95% CI: 1.09-1.76; I²=42.1%, p=0.008). DEHP and DBP phthalates showed the highest risks for urogenital malformations (OR: 3.12, 95% CI: 1.45-6.72). First trimester exposure demonstrated the strongest associations across malformation types. GRADE evidence was rated as moderate to high for urogenital and cardiac anomalies but low for gastrointestinal and neural defects.

CONCLUSIONS: Prenatal ED exposure is significantly associated with increased risk of surgical congenital malformations, particularly male urogenital and cardiac anomalies. These findings support implementing preventive strategies during pregnancy and justify stricter regulatory policies to protect fetal health and reduce the surgical burden in pediatric populations.

LEVEL OF EVIDENCE: II (Systematic Review and Meta-Analysis).

PMID:41308826 | DOI:10.1016/j.jpedsurg.2025.162829

Negative Paper Spray Ionization Mass Spectrometry for the Determination of Endocrine-Disrupting Chemicals with Application to Paraben Analysis in Cosmetics - November 27, 2025

Molecules. 2025 Nov 10;30(22):4356. doi: 10.3390/molecules30224356.

ABSTRACT

Paper spray ionization mass spectrometry (PSI-MS) enables rapid analysis with minimal sample preparation, yet negative-ion mode performance has been limited by poor sensitivity and unstable signals, similar to conventional electrospray ionization. In this study, we optimized negative PSI tandem MS (MS/MS) for twelve endocrine-disrupting chemicals (EDCs) and related biomarkers-including bisphenols, phthalates, parabens, and substituted phenols-used as model analytes. A systematic solvent and additive screen identified 1 mM ammonium fluoride in methanol and 0.1% ammonium hydroxide in 9:1 MeOH/carbon tetrachloride as optimal conditions, providing enhanced deprotonated-ion intensities and improved stability. Calibration curves generated under these conditions showed excellent linearity, with limits of quantitation (LOQs) in the low-ppb range. Application to cosmetic formulations demonstrated reliable paraben quantitation. In fortified hand cream, LOQs below 1 mg/kg were achieved, with recoveries of 93-110% and intra- and inter-day precision below 10% RSD. Notably, PSI-MS/MS performance was comparable to LC-MS/MS, without a separation step. These results demonstrate the feasibility of optimized negative PSI-MS as a sensitive and robust tool for paraben determination in cosmetics and highlight its potential as a versatile platform for broader EDC quantification.

PMID:41302415 | PMC:PMC12654611 | DOI:10.3390/molecules30224356

DBDPE inhibits myogenic differentiation of C2C12 cells through inhibiting mitochondrial function and PI3K/AKT/mTOR signaling pathway - November 27, 2025

Toxicol Lett. 2025 Nov 26;414:111783. doi: 10.1016/j.toxlet.2025.111783. Online ahead of print.

ABSTRACT

In recent years, decabromodiphenyl ethane (DBDPE), a type of brominated flame retardant, has gained popularity in industry as an alternative to decabromodiphenyl ether (BDEs). However, DBDPE exposure poses environmental pollution and primarily impacts muscle contraction and the reproductive endocrine system. The cellular implications and underlying mechanisms of DBDPE's effects on muscle remain poorly understood. In the present study, we investigated the effect of DBDPE on myoblast differentiation, apoptosis, as well as the potential mechanisms involved. The results demonstrated that exposure to DBDPE disrupted the differentiation of myotubes, inhibited cell proliferation, and increased levels of reactive oxygen species (ROS), ultimately leading to cell death. In addition, the RNAseq analysis revealed that DBDPE mainly affected the biological processes in mitochondria related to oxidative phosphorylation, ATP synthesis coupled electron transport, etc. Then we demonstrated that DBDPE inhibited mitochondrial membrane potential and ATP production, implying DBDPE resulted in mitochondrial dysfunction in C2C12 cells. Mechanistically, we showed that PI3K/AKT/mTOR signaling pathway was inhibited by DBDPE in C2C12 cells. And the apoptosis rate was significantly increased by DBDPE as demonstrated by increased active caspase-3 and TUNEL signal. Taken together, these findings suggest that low-dose exposure to DBDPE hampers myogenic differentiation and mitochondrial function, and increased cellular apoptosis through PI3K/AKT/mTOR signaling pathway, providing important insights for understanding its environmental toxic effects and conducting risk assessments.

PMID:41308956 | DOI:10.1016/j.toxlet.2025.111783

Endocrine Disruptors and Breast Cancer: A Comprehensive Review - November 27, 2025

Biomedicines. 2025 Nov 13;13(11):2774. doi: 10.3390/biomedicines13112774.

ABSTRACT

Breast cancer is one of the most prevalent malignancies affecting women worldwide. Among environmental risk factors, increasing attention has been given to endocrine-disrupting chemicals (EDCs), which can interfere with hormonal signaling pathways. Chronic exposure to these compounds, even at low doses, may lead to molecular changes that initiate carcinogenesis or promote tumor progression. Owing to EDCs' resistance to degradation and ability to bioaccumulate in organisms and the environment, they pose a growing concern for human health. They can mimic or block natural hormones by binding to receptors, such as estrogen, progesterone, aryl hydrocarbon, or thyroid-stimulating receptors, disrupting hormone synthesis, secretion, and metabolism. They have shown the ability to initiate carcinogenic changes in breast tissue or accelerate cancer progression. This review focuses on the relationship between EDC exposure and breast cancer, examining both their mechanisms of action and long-term health effects. Compounds such as polychlorinated biphenyls, parabens, phenols, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylhexyl phthalate, and bisphenol A, which are frequently encountered in everyday products, are discussed in detail. By presenting European Union guidelines and exploring EDCs' biological activity and pathways of endocrine disruption, we aimed to raise awareness of their potential risks and emphasize the need for further research.

PMID:41301867 | PMC:PMC12649852 | DOI:10.3390/biomedicines13112774

Impaired metabolic cooperation between oocyte and granulosa cells may contribute to the disrupted folliculogenesis and poor oocyte quality in PCOS - November 27, 2025

Life Sci. 2025 Nov 25;384:124117. doi: 10.1016/j.lfs.2025.124117. Online ahead of print.

ABSTRACT

BACKGROUND: Oocyte quality is largely governed by metabolic cooperation between oocytes and granulosa cells (GCs). PCOS is prevalent endocrine disorder in women of reproductive age, characterized by hyperandrogenaemia, skewed gonadotropins, insulin resistance, anovulation and poor oocyte quality. We aim to unravel glucose metabolism dynamics in oocyte microenvironment in PCOS compared to healthy controls undergoing IVF using follicular fluid (FF) and GCs.

METHODS: Glucose uptake by GCs was studied. Basal GLUT4 transcript and protein expression; and its translocation were assessed in GCs by immunofluorescence. Transcript levels of genes encoding metabolic enzymes, pyruvate levels and glycation markers were assessed in follicular environment. Real-time metabolic analysis was done using Seahorse XFe24 system.

RESULTS: Basal and stimulated glucose uptake, basal GLUT4 transcript and protein expression; and translocation on insulin stimulation were significantly lower in GCs from PCOS women. In PCOS follicle, glycolysis was downregulated as indicated by decreased transcript levels of rate-limiting enzymes, reduced pyruvate levels and lower real-time glycolysis and glycolytic capacity. Alternatively, pentose phosphate pathway, polyol pathway and glycation were increased and transcript levels of gap junctional proteins were downregulated in PCOS follicle. GCs from PCOS women showed increased oxidative stress and higher expression and nuclear translocation of NRF2.

CONCLUSION: Our data indicates inherent defects in metabolism in follicular compartment in women with PCOS which may affect oocyte quality. Understanding energy dynamics in the follicle can offer valuable insights about key metabolites to be added to oocyte/embryo culture media in IVF settings and may highlight plausible markers for oocyte/embryo quality.

PMID:41308869 | DOI:10.1016/j.lfs.2025.124117

Sex-Specific Molecular and Genomic Responses to Endocrine Disruptors in Aquatic Species: The Central Role of Vitellogenin - November 27, 2025

Genes (Basel). 2025 Nov 2;16(11):1317. doi: 10.3390/genes16111317.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are widespread contaminants that interfere with hormonal signaling and compromise reproductive success in aquatic organisms. Vitellogenin (VTG) is one of the most widely established biomarkers of estrogenic exposure, especially in males and juveniles. However, evidence from multi-omics studies indicates that VTG induction occurs within broader transcriptional and regulatory networks, involving genes such as cyp19a1 (aromatase), cyp1a (cytochrome P4501A), and other stress-responsive genes, underscoring the complexity of endocrine disruption. This review focuses on nuclear receptor isoforms, including estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and androgen receptor (AR) variants. We examine the diversification of vtg gene repertoires across teleost genomes and epigenetic mechanisms, such as DNA methylation and microRNAs, that modulate sex-dependent sensitivity. In addition, we discuss integrative approaches that combine VTG with transcriptomic, epigenetic, and histological endpoints. Within the Adverse Outcome Pathway (AOP) and weight-of-evidence (WoE) frameworks, these strategies provide mechanistic links between receptor activation and reproductive impairment. Finally, we outline future directions, focusing on the development of sex-specific biomarker panels, the integration of omics-based data with machine learning, and advances in ecogenomics. Embedding molecular responses into ecological and regulatory contexts will help bridge mechanistic insights with environmental relevance and support sustainability goals such as SDG 14 (Life Below Water).

PMID:41300770 | PMC:PMC12652119 | DOI:10.3390/genes16111317

Association between Endocrine Disruptors and Surgical Congenital Malformations: Systematic Review and Meta-Analysis - November 27, 2025

J Pediatr Surg. 2025 Nov 25:162829. doi: 10.1016/j.jpedsurg.2025.162829. Online ahead of print.

ABSTRACT

LEVEL OF EVIDENCE: II (Systematic Review and Meta-Analysis).

PMID:41308826 | DOI:10.1016/j.jpedsurg.2025.162829

Preliminary Identification of PFAS and Other Emerging Contaminants in the French Broad River, NC Post-Hurricane Helene - November 27, 2025

Toxics. 2025 Oct 22;13(11):905. doi: 10.3390/toxics13110905.

ABSTRACT

PMID:41304458 | PMC:PMC12656598 | DOI:10.3390/toxics13110905

Acrylamide-Induced Neuroendocrine Disruption in Adult Male Zebrafish (Danio rerio): Mechanistic Insights into Locomotor, Neuronal, and Reproductive Impairments - November 26, 2025

Mol Neurobiol. 2025 Nov 26;63(1):182. doi: 10.1007/s12035-025-05471-7.

ABSTRACT

Acrylamide (AA), a well-documented neurotoxin and reproductive toxicant in mammals, poses a potential risk to teleost species, yet its impact on the hypothalamic-pituitary axis and neuroendocrine integrity remains insufficiently explored. This study hypothesises that AA exposure disrupts locomotor behaviour, neurotransmitter homeostasis, and neuroendocrine regulation in adult male zebrafish, impairing reproductive fitness. Using 72 h exposure to 0.5 and 0.75 mM AA, we demonstrate significant alterations in acetylcholinesterase activity, dopamine levels, and Nos1 expression, correlating with locomotor and behavioural deficits. A marked decline in c-Fos immunoreactivity further suggests compromised neuronal activation associated with impaired mating behaviours. Notably, AA perturbs brain neuroendocrine gene expression, including kisspeptins (kiss1, kiss1rb, kiss2, kiss1ra), gnrh3, gonadotropins (fshb, lhb), estrogen receptors (esr1, 2a, 2b), and steroidogenic markers (cyp11a1, cyp17, hsd3b, cyp19a1b), corroborating well with reduced fertilisation efficiency. Mechanistically, oxidative stress characterised by elevated ROS and lipid peroxidation (MDA levels), dysregulated antioxidant systems (catalase, GST, Nox4, Nrf2/Keap1), and altered Cox2 expression drives JNK phosphorylation (activation), Bax/Bcl2 imbalance, Caspase activation, Parp1 cleavage, and DNA fragmentation, triggering brain apoptosis. Intriguingly, increased CD206 and Il-10 expression alongside suppressed proinflammatory mediators potentially hint at altered microglial polarisation and immune modulation in AA-treated brains. While current findings highlight AA-induced neurotoxicity and neuroendocrine disruption in zebrafish, in silico network toxicology analysis could identify AA-susceptible overlapping molecular targets and brain pathways impacting human neuronal and reproductive health. This study offers critical insights into the mechanistic basis of AA toxicity and its relevance in environmental health risk assessment.

PMID:41296176 | DOI:10.1007/s12035-025-05471-7

Adrenal Aging: Region-Specific Vulnerability and Proteostatic Decline - Mechanisms, Biomarkers, and Translational Opportunities - November 26, 2025

Aging Dis. 2025 Nov 21. doi: 10.14336/AD.2025.1296. Online ahead of print.

ABSTRACT

The adrenal gland integrates stress, metabolic, immune, and circadian signals to safeguard organismal homeostasis, yet its aging biology has been comparatively overlooked. Converging evidence from recent primate single-nucleus atlases, functional perturbations in human adrenal cells, human pathology, and multi-organ proteome aging resources reveals a coherent mechanistic picture: adrenal aging is region-specific, substrate-limited, and constrained by proteostasis, characterized by decline of dehydroepiandrosterone sulfate (DHEA-S) and aldosterone, while preserved cortisol output on average with diurnal flattening and higher prevalence of autonomous cortisol secretion with ageing. These endocrine trajectories implicate heightened vulnerability of the zona reticularis (ZR) and zona glomerulosa (ZG) versus the zona fasciculata (ZF). At the cellular level, ZR cells exhibit senescence, immune activation, and lipid metabolic disruption, including downregulation of androgen sulfation. Broad reduction of LDLR across cortex limits cholesterol import reduces DHEA-S, linking substrate scarcity to endocrine decline. Proteostatic lesions including aggresomes, amyloid, and lipofuscin accumulate across zones, aligning adrenal changes with systems-level proteome aging and vascular susceptibility. Key pathological correlates like ZR thinning, accumulation of aldosterone-producing cell clusters (APCCs), and higher prevalence of adrenal tumors underscore an age-biased remodeling of zonal identity and control hierarchies. Developmental and sex-dimorphic programs, including WNT/FRZB signaling and extracellular matrix remodeling, likely preconfigure later-life vulnerability. In this perspective, we synthesize these advances into a mechanistic model connecting centripetal differentiation, cholesterol trafficking, proteostasis collapse, inflammaging, and vascular aging to endocrine dysfunction and highlight biomarker strategies to index "adrenal age". We also outline near-term clinical deployment opportunities in older adults with adrenal incidentalomas or frailty using combined hormonal and plasma proteomic readouts, supported by human multi-organ proteomic evidence of proteostasis and vascular aging, aiming to restore cholesterol handling, reinforce proteostasis, and modulate senescence and niche signals.

PMID:41296927 | DOI:10.14336/AD.2025.1296

EndoCompass Project: Research Roadmap for Endocrine Causes and Consequences of Cancers - November 26, 2025

Horm Res Paediatr. 2025 Nov 26:1-16. doi: 10.1159/000549165. Online ahead of print.

ABSTRACT

BACKGROUND: Endocrine science remains underrepresented in European Union research programmes despite the fundamental role of hormone health in human wellbeing. Analysis of the CORDIS database reveals a persistent gap between the societal impact of endocrine disorders and their research prioritisation. At the national funding level, endocrine societies report limited or little attention of national research funding towards endocrinology. The EndoCompass project - a joint initiative between the European Society of Endocrinology and the European Society of Paediatric Endocrinology - aimed to identify and promote strategic research priorities in endocrine science to address critical hormone-related health challenges.

METHODS: Research priorities were established through comprehensive analysis of the EU CORDIS database covering the Horizon 2020 framework period (2014-2020). Expert consultation was conducted to identify key research priorities, followed by broader stakeholder engagement including society members and patient advocacy groups.

RESULTS: Research priorities encompass re-evaluation of progestins in breast cancer treatment; strategies to disrupt AR signalling in prostate cancer; surveillance for endocrine sequelae in childhood cancer survivors; understanding genotoxic effects on fertility; and management of checkpoint inhibitor endocrinopathies and familial cancer syndromes. Emphasis is placed on precision medicine and metabolic factors in cancer.

CONCLUSIONS: This component of the EndoCompass project provides an evidence-based roadmap for strategic research investment. This framework identifies crucial investigation areas into cancer-endocrine pathophysiology, prevention, and treatment strategies, ultimately aimed at reducing the burden of these disorders on individuals and society. The findings support the broader EndoCompass objective of aligning research funding with areas of highest potential impact on endocrine health.

PMID:41296658 | DOI:10.1159/000549165

Presence of toxic organic substances in antarctic wildlife as an indicator of human impact in the South Shetland Islands area (Western Antarctic) - November 26, 2025

J Hazard Mater. 2025 Nov 21;500:140567. doi: 10.1016/j.jhazmat.2025.140567. Online ahead of print.

ABSTRACT

Endocrine-disrupting compounds (EDCs), including bisphenol A (BPA), 4-nonylphenol (4-NP), 4-tert-octylphenol (4-t-OP), polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and polycyclic aromatic hydrocarbons (PAHs), pose a significant risk to wildlife due to their ability to bioaccumulate through trophic webs, affecting reproduction, development, and survival. While their presence in Antarctic waters has been documented, data on their accumulation in penguin-derived materials such as feathers, guano, and eggshells remain limited. This study aimed to assess the presence of phenolic compounds (BPA, 4-NP, 4-t-OP) in Pygoscelis penguin derivatives as indicators of anthropogenic influence, and to examine the presence of PAHs, PCBs, and HCB to evaluate the effectiveness of regulatory measures. Non-invasive samples from Pygoscelis penguins on King George Island were collected during the austral summer of 2023/2024 and analyzed using HPLC-FLD and GC-ECD/FID. BPA was detected in 82 % of samples at the highest concentrations, followed by 4-NP (76 %) and 4-t-OP (41 %), with the highest levels found in chicks. PCBs and HCB were largely undetected, suggesting regulatory success, while PAHs were consistently found in guano, indicating ongoing local pollution. These findings highlight the ecological risks of anthropogenic contaminants and support continued non-invasive monitoring to inform conservation efforts in the Antarctic.

PMID:41297256 | DOI:10.1016/j.jhazmat.2025.140567

Deep learning-integrated SERS platform for accurate identification of diverse phthalate ester subtypes - November 26, 2025

J Hazard Mater. 2025 Nov 22;500:140584. doi: 10.1016/j.jhazmat.2025.140584. Online ahead of print.

ABSTRACT

Phthalate esters (PAEs) are widely employed as plasticizers to enhance the durability, flexibility, and processability of polymer-based materials. Because PAEs do not form covalent bonds with polymer matrices, they can readily migrate into the environment. This raises significant ecological issues and human health concerns such as endocrine disruption and developmental toxicity. In this study, we developed a surface-enhanced Raman spectroscopy (SERS)-based analytical platform integrated with deep learning algorithms for the rapid and accurate identification and classification of seven representative PAEs. Plasmonic gold nanopillar (AuNP) substrates were engineered to form vertically and horizontally oriented nanogap structures that generate intense localized electromagnetic hotspots, substantially amplifying the Raman signals of adsorbed PAEs. Comprehensive spectral datasets were collected through SERS detection using a portable Raman spectrometer. Deep neural network (DNN) models trained on these data achieved robust classification performance with an accuracy of 99.4 % across all PAE species. Furthermore, SHapley Additive exPlanations (SHAP) analysis provided interpretable insights into the most discriminative Raman spectral features driving the model predictions. The platform was successfully applied to detect PAEs in commercially available consumer products at concentrations near the regulatory threshold of 0.1 % (w/w) established by regulatory bodies such as the European Union's RoHS Directive and the US CPSIA. These findings demonstrate that the integration of nanostructure-enhanced SERS and deep learning constitutes a powerful, high-throughput, and field-deployable approach for reliable PAE detection, with broad applicability in environmental monitoring, consumer product safety evaluation, and regulatory compliance.

PMID:41297261 | DOI:10.1016/j.jhazmat.2025.140584

Integrated Approaches to Testing and Assessment for the Endocrine Disrupting Activity of Tartrazine based on Adverse Outcome Pathways and OECD Frameworks - November 26, 2025

Food Chem Toxicol. 2025 Nov 24:115867. doi: 10.1016/j.fct.2025.115867. Online ahead of print.

ABSTRACT

Tartrazine (TTZ), a widely used synthetic azo dye in processed foods, beverages, and pharmaceuticals, raises various health concerns including hematotoxicity, genotoxicity, carcinogenicity, neurotoxicity, and endocrine activity. Regarding the endocrine disruption, although individual studies has reported estrogenic, androgenic and thyroid effects, a comprehensive and integrated evaluation of across hormonal systems have never been tried. To address this gap, we performed multi-tool in silico approaches covering all nuclear receptors. Docking simulations (Endocrine Disruptome, CB-Dock2, and AutoDock Vina) were employed to estimate receptor-binding propensities. Machine learning-based resources (ADMETlab3.0, ProTox-3.0, CERAPP/CoMPARA, and EDC-Predictor) were used to forecast endocrine activities. Most nuclear receptors exhibited potential effects by TTZ-including AR, ERα, TRα/β, PXR, RXRα, PPARγ, and AhR-except ERβ. Consistently, ToxCast reported active calls for AR, ERα, TR, RXR, and AhR. In addition, SwissTargetPrediction and PharmMapper indicated that TTZ could predominantly influence reproductive and thyroid toxicity via cancer-related pathways. We further aligned in silico outputs with existing in vitro and in vivo findings mapped to AOPs for the estrogen, androgen, and thyroid axes, and summarized evidence across hormonal systems under OECD-relevant considerations to clarify current knowledge and guide future systematic endocrine profiling of TTZ.

PMID:41297657 | DOI:10.1016/j.fct.2025.115867

Environmental Determinants of Early Childhood Caries: A Narrative Synthesis of Observational Evidence and Implications for Global Policy - November 26, 2025

Dent J (Basel). 2025 Oct 22;13(11):484. doi: 10.3390/dj13110484.

ABSTRACT

Early childhood caries (ECC) remains a significant global health challenge, disproportionately affecting marginalized populations. While traditional research emphasizes behavioral and biological risk factors, emerging evidence highlights the critical role of environmental determinants. This narrative synthesis aims to highlight the role of environmental determinants as a risk factor for ECC pathogenesis. Environmental toxins (e.g., lead, perfluoroalkyl acids, tobacco smoke, air pollution) disrupt enamel development, impair salivary function, and compromise immune responses, directly increasing caries susceptibility. Environmental degradation, including air pollution, reduces ultraviolet B radiation exposure, limiting endogenous vitamin D synthesis that is vital for enamel mineralization and immune regulation. These risks are compounded in low- and middle-income countries, where structural inequities, inadequate sanitation, and climate disruptions exacerbate ECC burdens. We introduce ecovitality-the resilience of ecosystems supporting human health-as a novel framework linking ecological vitality to oral health. Degraded environments limit access to fluoridated water and nutrient-dense foods while promoting sugary diets and endocrine disruptors. A One Health approach is advocated to address interconnected environmental, social, and biological determinants of the risk for ECC. Despite global reductions in tobacco use and lead exposure, the Global Burden of Disease 2021 analysis reports stagnation in ECC prevalence. This underscores the critical need for longitudinal and mechanistic studies to establish causality, quantify the contributions of environmental controls, and explore how mitigating these risks can reduce the global ECC burden. Such evidence may promote interdisciplinary action to align oral health promotion for children with the Sustainable Development Goals.

PMID:41294465 | PMC:PMC12651089 | DOI:10.3390/dj13110484

Final Heights in Patients with Congenital Adrenal Hyperplasia: a Retrospective Cohort Study - November 26, 2025

J Prev Med Hyg. 2025 Oct 31;66(3):E382-E390. doi: 10.15167/2421-4248/jpmh2025.66.3.3455. eCollection 2025 Sep.

ABSTRACT

INTRODUCTION: Congenital adrenal hyperplasia (CAH) attributed to 21-OHD is one of the most common genetic endocrine disorders that occurs due to the disruption and defects in the steroidogenic enzymes involved in the production of cortisol. The current study aims to assess the final height of patients with classic CAH forms in Iran.

METHODS: The retrospective cohort study was conducted on 30 patients (determined using the previous studies by the sample size formula to compare two means) studies with classic type CAH who were followed up and treated in the endocrinology clinic of Ali Asghar Hospital during the 2000-2022 years. The history of the patients at the time of diagnosis was extracted from the patient's files and recorded in the checklist. All data was analyzed using IBM SPSS Statistics version 22 software.

RESULTS: In the simple virilizing (SV) group, the target and final height for females was 162 and 159.2 cm, and for males were 173 and 171 cm. In the salt-wasting (SW) group, the target and final height for females was 164 and 163.2 cm, and for males were 171.7 and 173.1 cm. There was a significant and reverse correlation between the mean age at the time of diagnosis and the Final Height percentile among all cases (r: -0.55, p: 0.02) and the SW group (r: -0.75, p: 0.002). A positive and significant correlation was seen between the bone age advanced and final height percentile in the SV group (r: 0.04, p: 0.03). The final height percentile increased significantly with an increase in the Duration of treatment regardless of CAH type (r: -0.67, p: 0.009). Also, there was a positive and significant correlation between hydrocortisone dose and final height percentile in the SV group (r: 0.24, p: 0.04).

CONCLUSION: The results of the present study showed that early diagnosis of the disease at a young age, lower bone age of patients, preventing the increase of obesity in children with CAH, and receiving appropriate drugs with standard doses can play an effective role in increasing the final height of CAH patients.

PMID:41292542 | PMC:PMC12643077 | DOI:10.15167/2421-4248/jpmh2025.66.3.3455

AOH induces oxidative stress and DNA damage in ovarian cancer cells via modulation of GPER1 and HIF1α/PI3K/CLDNs signaling pathway - November 26, 2025

Sci Rep. 2025 Nov 26;15(1):42138. doi: 10.1038/s41598-025-26042-9.

ABSTRACT

Claudins (CLDNs) are small proteins that form tight junctions (TJs) in cells and play a key role in various biological processes in cells. Previous results have shown that CLDNs expression can be regulated by hormones and, therefore, can also be regulated by compounds that mimic their action. Such compounds belong to a large group called endocrine-disrupting chemicals (EDCs). Alternariol (AOH), an emerging mycotoxin, contaminates various food products. AOH is reported to be genotoxic and to induce oxidative stress. Previous results showed that AOH is also estrogenic and acts as an androgen receptor (AR) agonist, suggesting that it might act as one of the EDCs, however, its detailed molecular mechanism has not been fully elucidated yet. In this study, we decided to evaluate the interplay between AOH and G protein-coupled estrogen receptor 1 (GPER1) in hormone-dependent human ovarian cancer (OC) cells with a focus on the involvement of hypoxia-inducible factor 1-alpha/phosphoinositide 3-kinases/protein kinase B (HIF1α/PI3K/Akt) and claudins (CLDNs) signaling pathways in that effect. We observed that AOH induces oxidative stress and DNA damage in OC cells, and this effect is partially mediated by GPER1. We found that the GPER1 antagonist G15 partially mitigated AOH-induced ROS production and significantly reduced DNA damage, confirming the receptor's role in mediating these effects. Furthermore, we observed the involvement of HIF1α/PI3K/Akt and CLDNs pathways in AOH effect in OC cells. In conclusion, we postulate that AOH has pro-oxidative ability and that this effect is partially mediated by GPER1. Moreover, we postulated that HIF1α/PI3K/Akt and CLDNs participate in AOH action in OC cells, which in turn provides useful information for future toxicological research studies as a new molecular mechanism of AOH.

PMID:41298511 | PMC:PMC12658207 | DOI:10.1038/s41598-025-26042-9

Microbiome Mediated Immune Crosstalk on the Gut-Thyroid Axis in Autoimmune Thyroid Disease - November 26, 2025

Immunol Invest. 2025 Nov 26:1-21. doi: 10.1080/08820139.2025.2593335. Online ahead of print.

ABSTRACT

BACKGROUND: The gut microbiota plays an important role in systemic immune homeostasis and is increasingly implicated in autoimmune thyroid disease (AITD). Evidence suggests that gut dysbiosis, impaired intestinal barrier function, and altered microbial metabolites particularly short-chain fatty acids contribute to immune imbalance along the gut-thyroid axis. Although molecular mimicry between microbial and thyroid antigens has been proposed, current human evidence remains associative rather than causal.

METHODS: This review synthesized current observational, translational, and preclinical studies evaluating microbial composition, barrier integrity, microbial metabolites, and immune pathways relevant to AITD. Mechanistic insights into T-lymphocyte regulation and microbial-host interactions were integrated with emerging interventional data.

RESULTS: Gut dysbiosis in AITD is linked to reduced regulatory T-lymphocytes, expansion of Th17 cells, increased intestinal permeability, and the loss of short-chain-fatty-acid-producing taxa. Observational studies consistently report disease-associated taxonomic alterations, while preclinical models support causal pathways through barrier disruption and microbiota-driven immune activation. Early interventional approaches such as high-fiber dietary patterns, probiotics, prebiotics, and experimental fecal microbiota transplantation show modest reductions in thyroid autoantibodies in small trials, though effects are strain-specific, short-term, and not disease-modifying.

CONCLUSION: Despite largely associative human evidence, converging mechanistic findings highlight the gut microbiota as a modifiable contributor to thyroid autoimmunity. Future priorities include clarifying causality, identifying keystone microbial taxa and metabolites, and establishing standardized interventional frameworks to facilitate translation into endocrine practice.

PMID:41292506 | DOI:10.1080/08820139.2025.2593335

Chromogranin A and catestatin regulate pancreatic islet homeostasis, endocrine function, and neurotransmitter signaling - November 26, 2025

Commun Biol. 2025 Nov 26;8(1):1684. doi: 10.1038/s42003-025-09135-z.

ABSTRACT

Chromogranin A (CgA), a neuroendocrine pro-hormone, is proteolytically cleaved into bioactive peptides, most notably catestatin (CST) and pancreastatin (PST), which exert opposing effects on metabolic and inflammatory processes. Using CgA- and CST knockout (KO) mice, we investigated the roles of these peptides in pancreatic endocrine function, morphology, neurotransmitter dynamics, and systemic glucose homeostasis. CST-KO mice displayed impaired insulin secretion in vivo (but not ex vivo), disrupted islet architecture, and elevated catecholamine levels. In contrast, CgA-KO mice, which lack both CST and PST, exhibited reduced beta-cell mass but improved insulin sensitivity due to absence of PST. Peptide supplementation experiments in CgA-KO mice revealed that CST suppressed gluconeogenesis and enhanced glucagon regulation, whereas PST promoted insulin resistance and glucose production. Spatial mass spectrometry further demonstrated altered neurotransmitter and polyamine profiles in KO islets, implicating disrupted nerve-immune-islet crosstalk as a contributor to the observed metabolic phenotypes. Collectively, these findings identify CgA-derived peptides as critical regulators of islet function and highlight CST as a promising therapeutic candidate for diabetes and metabolic-inflammatory disorders.

PMID:41298823 | PMC:PMC12658243 | DOI:10.1038/s42003-025-09135-z

Endocrine Disrupting Chemicals in Human Milk: A Systematic Review of Concentrations and Potential Health Implications - November 25, 2025

Curr Environ Health Rep. 2025 Nov 25;12(1):48. doi: 10.1007/s40572-025-00515-5.

ABSTRACT

PURPOSE OF REVIEW: Endocrine-disrupting chemicals (EDCs) disrupt the synthesis, transport, action, or metabolism of endogenous hormones in the human body. EDCs often enter the body through inhalation, ingestion, or dermal contact and can accumulate in the body. Remobilization or transfer of EDCs can occur during lactation, causing human milk to become contaminated with a variety of EDCs, which could expose nursing infants and children to these chemicals.

RECENT FINDINGS: Several studies have examined the concentration ranges for one or multiple EDC(s) in human milk. Additional studies document associations between EDC exposure and adverse health outcomes, many of which are in adult populations. It is therefore essential to understand the extent to which EDCs in human milk contribute to cumulative early-life exposures.

SUMMARY: We performed a literature review of peer-reviewed studies reporting concentrations of one or more of the following EDCs in human milk during or after 2004: bisphenols, organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs), parabens, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and phthalates. We identified concentration ranges for each chemical detected in human milk and health impacts associated with early-life exposures to EDCs noted across studies from this review. Determining the presence of EDCs in human milk and the associated effects of exposure through nursing is essential to develop feeding recommendations that safeguard infant and child health.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40572-025-00515-5.

PMID:41286197 | PMC:PMC12644229 | DOI:10.1007/s40572-025-00515-5

Research progress on the human exposure levels and health risks of butylated hydroxytoluene and its metabolites - November 25, 2025

Zhonghua Yu Fang Yi Xue Za Zhi. 2025 Nov 6;59(11):1972-1977. doi: 10.3760/cma.j.cn112150-20250421-00336.

ABSTRACT

Butylated hydroxytoluene (BHT) is a synthetic phenolic antioxidant widely used in food additives, pharmaceuticals, personal care products, and other industries. It has been frequently detected in various environmental media, including oceans, soils, and the atmosphere. Human exposure to BHT can occur through multiple routes, and it has the potential to accumulate in the body while being readily transformed into several metabolites that are often more toxic than the parent compound. In recent years, numerous studies have investigated the levels of BHT and its metabolites in human populations and their potential health risks. Most current research on BHT exposure and its metabolites has focused on vulnerable groups such as pregnant women and children. These compounds have been detected in various biological samples-including human serum, urine, cerebrospinal fluid, and placenta-with relatively high frequencies.The metabolites of BHT demonstrate greater toxicity than BHT itself and have been implicated in pathological processes such as diminished ovarian reserve and miscarriage. Potential mechanisms include endocrine disruption, oxidative stress, and DNA damage. This article reviews current research on human exposure to BHT and its metabolites, as well as their potential health effects, aiming to provide a scientific basis for establishing usage standards and assessing health risks associated with BHT.

PMID:41287337 | DOI:10.3760/cma.j.cn112150-20250421-00336

Subacute Trends in Metabolic and Hematological Markers Days After Severe Traumatic Brain Injury Predict Long-Term Outcomes - November 25, 2025

Neurosurgery. 2025 Nov 25. doi: 10.1227/neu.0000000000003863. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Prognostic models for severe traumatic brain injury (TBI) patients do not perform well enough to be clinically useful, possibly because included predictors for the most well-established models are from hospital presentation only. We sought to investigate fluctuations in metabolic and hematological markers over the subacute time period (ie, up to 14 days postinjury) and associate these changes with functional outcome at 6 months postinjury.

METHODS: This cohort study included prospectively collected patients with severe TBI treated at a single level I trauma center (n = 315). Measured metrics included basic vitals (eg, heart rate), arterial blood gases, basic metabolic panel (eg, glucose, sodium), blood counts (eg, hemoglobin, platelets), and endocrine panels (eg, cortisol) taken periodically from admission to 14 days postinjury. Functional outcome was defined as Glasgow Outcome Scale-Extended score at 6 months. Random forest regression trees were used to associate these markers to outcome. Model performance was compared to using International Mission on Prognosis and Analysis of Clinical Trials metrics collected on hospital admission.

RESULTS: The International Mission on Prognosis and Analysis of Clinical Trials model predicted 6-month Glasgow Outcome Scale-Extended with a coefficient of determination (R2; ie, variance accounted for) of approximately 19%. Incorporation of subacute biomarker trends improved model performance by 8% (R2 = 27%). Fluctuations in glucose, sodium, and platelets over the first 2 weeks postadmission formed reliable patterns across participants and correlated significantly with eventual outcomes (correlation = -0.3 to -0.4 for sodium and glucose, correlation = +0.2 to +0.3 for platelets). In a subset of participants, fluctuations in glucose and platelets were associated to cortisol levels taken within 48 hours of admission.

CONCLUSION: Fluctuations in several hematological and metabolic markers over the days to weeks after severe TBI form consistent patterns that can be linked to endocrinological disruptions and 6-month functional outcome.

PMID:41288377 | DOI:10.1227/neu.0000000000003863

Interfacial Host-Guest Recognition at Poly(sulfobutyl-β-cyclodextrin)-Macroporous Carbon: A Supramolecular Electrochemical Protocol for Nitrophenol Isomers Sensing - November 25, 2025

Langmuir. 2025 Nov 25. doi: 10.1021/acs.langmuir.5c04325. Online ahead of print.

ABSTRACT

Owing to their inherent stability, nitrophenol isomers (NPs) persist and accumulate in the environment, posing critical ecosystem risks through bioaccumulation and endocrine disruption, and thus advanced detection methods are urgently needed. Herein, we describe the fabrication of poly(sulfobutyl-β-cyclodextrin)-functionalized macroporous carbon (PSBCD-MPC) immobilized on a glassy carbon electrode (GCE), enabling discrimination of ternary nitrophenol isomers in aqueous environmental matrices. The differential pulse voltammetry (DPV) response of PSBCD-MPC interface toward three nitrophenol isomers showed three separated electrochemical signals with distinct linear ranges of 1-180 μM for o-nitrophenol (o-NP), 1-200 μM for both m-nitrophenol (m-NP) and p-nitrophenol (p-NP), and relatively lower detection limits (LOD) of 0.28 μM for o-NP, 0.22 μM for m-NP, and 0.31 μM for p-NP, respectively. The macroporous architectures of MPC establish rapid mass-transfer and electron-transfer highways, while the strategic integration of PSBCD moieties within the conductive matrix enables differentiated host-guest recognition. This synergy facilitates precise discrimination of nitrophenol isomers through a combination of host-guest interactions and electrochemical interfacial microenvironment effects, providing a robust platform for their selective detection. Furthermore, the constructed PSBCD-MPC sensing interface exhibited recoveries of 95.0-104.6% in real aqueous matrices, demonstrating field-applicable potential for simultaneous nitrophenol isomer monitoring.

PMID:41289362 | DOI:10.1021/acs.langmuir.5c04325

Preparation of carbon sphere/nickel/boron doped diamond electrode for highly sensitive electrochemical detection of estriol - November 25, 2025

Talanta. 2025 Nov 21;299:129148. doi: 10.1016/j.talanta.2025.129148. Online ahead of print.

ABSTRACT

Estriol (E3) is one of the endocrine disruptors, its continuous emission poses risks to the environment, thus, it is necessary to conduct sensitive and real-time detection. In this work, boron-doped diamond (BDD) is modified with carbon spheres (CS) and metallic nickel to fabricate the CS/Ni-BDD electrode for achieving high-performance electrochemical detection of E3. The CS/Ni-BDD electrode exhibits high sensitivity (a linear detection range of 0.5-10 μM and 10-100 μM, a low detection limit of 0.13 μM, and high sensitivity of 2.66 μA μM^-1 cm^-2), which is attributed to the synergistic effect of BDD substrate with a low background current and CS modifier with the abundant surface-active sites. In addition, the detection of E3 in buffer solutions, actual environmental samples, as well as the repeatability test, shows that the electrode exhibits high sensitivity, good repeatability and promising practical application.

PMID:41289781 | DOI:10.1016/j.talanta.2025.129148

Prioritising research on endocrine disruption in the marine environment: a global perspective - November 25, 2025

Biol Rev Camb Philos Soc. 2025 Nov 25. doi: 10.1111/brv.70106. Online ahead of print.

ABSTRACT

A healthy ocean is a crucial life support system that regulates the global climate, is a source of oxygen and supports major economic activities. A vast and understudied biodiversity from micro- to macro-organisms is integral to ocean health. However, the impact of pollutants that reach the ocean daily is understudied for marine taxa, which are also absent or poorly represented in regulatory test guidelines for chemical hazard assessment. Inspired by the United Nations Decade of Ocean Science, which aims to reverse the decline in ocean health, this communication calls for global coordination in building resources for studying the effects of marine pollution. The bibliographic analysis, a collective product of scientists from diverse backgrounds, focused on endocrine-disrupting chemicals (EDCs). In this review, we (i) critically analyse the literature on endocrine signalling pathways and high-level physiological impacts of EDCs across 20 representative marine taxa; (ii) identify knowledge and regulatory gaps; (iii) apply bioinformatics approaches to marine species genomic resources, with relevance for predictions of susceptibility; and (iv) provide recommendations of priority actions for different stakeholders. We reveal that the scientific literature on EDCs is biased towards terrestrial and/or freshwater organisms, is limited to a handful of animal taxa, and marine organisms are dramatically underrepresented. Our bibliographic analysis also confirmed that only a small number of (neuro) endocrine pathways are covered for all animals, whilst basic knowledge on endocrine systems/endocrine disruption for most marine invertebrate phyla is minimal. Despite significant gaps in genomic resources for marine animals, endocrine-related protein conservation was evident across more than 500 species from diverse marine taxa, highlighting that they are at risk from EDCs. Despite recent technological advances, translation of existing knowledge into international regulatory test guidelines for chemical hazard assessment and monitoring programs is limited. Furthermore, the current understanding is confounded in part by transposing vertebrate endocrinology onto non-vertebrate taxa. In this context, specific recommendations are provided for all stakeholders, including academia (e.g. to expand knowledge across metazoan taxa and endocrine targets and translate it to New Approach Methodologies and Adverse Outcome Pathways; to increase and improve tools for comparative species-sensitivity distributions and cross-species extrapolations), regulators (e.g. increase awareness of specific risks for the marine environment, prioritise international standardisation of testing methods for marine species and request evidence for absence of endocrine disruption in marine phyla), policy makers (e.g. implement sustained, long-term international marine monitoring programs and increase global co-operation) and the public or non-governmental organisations (e.g. foster public engagement and behaviours that prevent marine chemical pollution; promote citizen science activities; and drive political actions towards protective and restorative marine policies). We hope that this and past reviews can contribute towards meeting ambitious international plans for marine water quality assurance, mitigation of marine pollution impacts and protection of marine biodiversity. The importance of marine biodiversity for climate change mitigation, food security and sustainable ecosystem services calls for urgent, cooperative action.

PMID:41290225 | DOI:10.1111/brv.70106

Occurrence, fate and ecological risks of phthalate esters and bisphenol A in coastal wastewater discharges - November 25, 2025

Sci Rep. 2025 Nov 25;15(1):41796. doi: 10.1038/s41598-025-25697-8.

ABSTRACT

This study examines the occurrence and ecological risks of phthalate esters (PAEs) and bisphenol A (BPA) in raw urban wastewater from Bushehr, a coastal city in the northern Persian Gulf. PAEs, used as plasticizers, and BPA, found in various consumer products, are endocrine disruptors that pose environmental and health threats. The research evaluates the concentrations, distribution, and sources of these pollutants and assesses their ecological risks. Wastewater samples were collected from six discharge stations along the Bushehr coastline between February and April 2023. Using gas chromatography-mass spectrometry (GC-MS), seven PAE compounds, including dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP), and di-octyl phthalate (DOP), alongside BPA were analyzed. DEHP emerged as the dominant PAE, with concentrations ranging from 19.67 to 39.75 µg/L, while BPA levels ranged from 0.10 to 2.50 µg/L, peaking at Rishehr Park. Ecological risk assessment, conducted using the risk quotient (RQ) method, revealed that DEHP posed a high ecological risk (RQ > 1) to sensitive aquatic species. These findings highlight the urgent need for improved wastewater treatment and pollution control to safeguard marine ecosystems and public health. The study contributes valuable insights into the contamination levels and sources of PAEs and BPA in the northern Persian Gulf, advancing the understanding of regional marine pollution and its ecological impacts.

PMID:41290789 | PMC:PMC12647256 | DOI:10.1038/s41598-025-25697-8

Protective effects of 20(R) ginsenoside Rg3 on DBP-induced reproductive injury in mice through Nrf2/ARE pathway - November 25, 2025

Sci Rep. 2025 Nov 24;15(1):41658. doi: 10.1038/s41598-025-25606-z.

ABSTRACT

Di-n-butyl phthalate (DBP), an environmental endocrine disruptor, can induce male reproductive dysfunction. In the study, the protective mechanism of ginsenoside Rg3 (Rg3) against DBP-induced damage to spermatogenic function was explored through the Nrf2/antioxidant response element (ARE) signaling pathway in mice. The protective effects of Rg3 were analyzed by comparing the quality of sperm, the levels of reproductive hormones and the mRNA and protein expression of Nrf2, NQO1, and StAR in the testicular tissue. The results showed that Rg3 restored the reproductive damage caused by DBP, improved the thesticular structure, enhanced the number and motility of sperm, and upregulated the mRNA expression levels of Nrf2, NQO1, StAR and increased the phosphorylation of proteins in testicular tissue. Ginsenoside Rg3 can activate the Nrf2/ARE pathway, upregulate NQO1, regulate StAR protein expression, and has a relieving effect on DBP-induced reproductive dysfunction in mice. Rg3 may become a potential therapeutic drug for male infertility due to environmental toxicants.

PMID:41285908 | PMC:PMC12644513 | DOI:10.1038/s41598-025-25606-z

Endocrine Disrupting Chemicals in Human Milk: A Systematic Review of Concentrations and Potential Health Implications - November 25, 2025

Curr Environ Health Rep. 2025 Nov 25;12(1):48. doi: 10.1007/s40572-025-00515-5.

ABSTRACT

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40572-025-00515-5.

PMID:41286197 | PMC:PMC12644229 | DOI:10.1007/s40572-025-00515-5

Determination of bisphenol a in doogh (a yogurt-based Iranian drink) by magnetic-SPE (MWCNT-Fe3O4)/GC-MS method and human health risk assessment - November 25, 2025

Sci Rep. 2025 Nov 24;15(1):41672. doi: 10.1038/s41598-025-25638-5.

ABSTRACT

Doogh is a traditional Iranian yogurt-based drink that is served flavored or unflavored and carbonated or non-carbonated. Bisphenol A (BPA) is an endocrine disrupting analyte, which poses significant dangers to public health. The goal of our investigation was to assess the BPA content in doogh samples from Tehran along with risk assessment by using the Monte Carlo method. A nano-adsorbent of magnetized iron-based multi-walled carbon nanotubes (MWCNT-Fe₃O₄) was used with gas chromatography-mass spectrometry (GC/MS) to evaluate the mentioned contaminant. The average amount of BPA in doogh samples was 3.50 µg/L (ranged 0.63 to 6.75 µg/L). BPA concentrations in all doogh samples were within the standard limit. In addition, the health risks of BPA intake through doogh were assessed. The results of multivariate statistical evaluation highlighted the relationship between BPA concentrations and independent variables (volume, brand, packaging type, storage conditions, pH, fat, salt, and trans fatty acid content). According to the updated tolerable daily intake (TDI) established by the European Food Safety Authority (EFSA), the 50th percentile for the target hazard quotient of BPA in doogh samples was 2.22E + 0 for adults and 7.83E + 0 for children (THQ > 1). This evidence suggests chronic consumption of doogh from plastic or metal containers may endanger human health. The intake of BPA through doogh samples poses adverse health risks to Iranian consumers.

PMID:41285985 | PMC:PMC12644895 | DOI:10.1038/s41598-025-25638-5

Metabolomics-Based Diagnosis of Medullary Thyroid Cancer: A Plasma 1H NMR Approach - November 24, 2025

Iran J Public Health. 2025 Sep;54(9):2005-2014. doi: 10.18502/ijph.v54i9.19867.

ABSTRACT

BACKGROUND: Medullary thyroid cancer (MTC) is a rare neuroendocrine malignancy, accounting for 5-10% of all thyroid cancer cases. The precise molecular processes driving MTC remain largely elusive. We aimed to conduct a pilot study analyzing plasma metabolic profiles of MTC patients to uncover disruptions in metabolic pathways that may contribute to MTC tumorigenesis.

METHODS: Proton nuclear magnetic resonance (1H-NMR) spectroscopy was performed to screen metabolic changes in plasma samples from MTC patients (n=16) and healthy subjects (n=12). Multivariate and univariate analyses were applied using MetaboAnalyst and SIMCA software.

RESULTS: A total of 30 compounds were identified, of which three metabolites-glycerol, isobutyric acid, and valine-showed significant differences between MTC patients and the control group (P<0.05).

CONCLUSION: The findings from this study contribute to the current understanding of MTC metabolism and suggest that the NMR-based metabolomics approach can provide a metabolic pattern of MTC, potentially improving diagnostic procedures.

PMID:41277929 | PMC:PMC12630391 | DOI:10.18502/ijph.v54i9.19867

Screening and prioritization of endocrine-disrupting chemicals in plastic toys for children based on non-target analysis and machine learning predictive model - November 24, 2025

Environ Int. 2025 Nov;205:109878. doi: 10.1016/j.envint.2025.109878. Epub 2025 Oct 23.

ABSTRACT

The health risks associated with the exposure of infants to harmful chemicals, particularly endocrine disruptors, in plastic toys have garnered widespread attention; however, the corresponding knowledge remains limited. In this study, we employed a non-target analysis approach alongside Toxicological Priority Index (ToxPi) model based on toxicity data predicted by machine learning predictive model to systematically screen and prioritize endocrine-disrupting chemicals (EDCs) in plastic toys for very young children (n = 45). A total of 165 compounds were identified and classified into five categories: additives (30.3 %), processing aids (13.3 %), monomers and intermediates of synthetic plastics (11.5 %), non-intentionally added substances (10.9 %), and uncategorizable chemicals (33.9 %). Among these, antioxidants, plasticizers, flame retardants, and surfactants were widely detected. Emerging non-phthalate plasticizers and non-intentionally added drugs were reported for the first time in this study. In addition to the known EDCs (e.g., phthalates), the endocrine disruption prediction results indicated that antioxidants (n = 8) and antibacterial agents (n = 2) exhibited high ToxPi scores among the identified chemicals. Further, exposure risk index was calculated by incorporating both ToxPi scores and the peak intensities of the compounds identified above. Toys made from polyethylene terephthalate, silicone, acrylonitrile-butadiene-styrene, and polystyrene had higher risk index compared with those made from polypropylene. The antibacterial agent ethyl sorbate, antioxidant Irganox 1010, therapeutics/prescription drugs dienogest, and antibacterial agent chalcone were identified as top priority EDCs in each material. This study highlights the urgent need to assess the exposure risks for infants through plastic toys and to implement control measures for emerging EDCs in plastic toys for very young children.

PMID:41284517 | DOI:10.1016/j.envint.2025.109878

Androgen receptor mutations in familial androgen insensitivity syndrome: A metabolic reprogramming pathway to type 2 diabetes susceptibility - November 24, 2025

World J Diabetes. 2025 Nov 15;16(11):112236. doi: 10.4239/wjd.v16.i11.112236.

ABSTRACT

Familial androgen insensitivity syndrome (AIS), resulting from inherited mutations in the androgen receptor (AR) gene, has traditionally been examined within the framework of disorders of sex development. However, growing evidence indicates that AR dysfunction also disrupts systemic metabolic homeostasis, predisposing affected individuals to insulin resistance and type 2 diabetes mellitus. This article synthesizes recent advances in genetics, transcriptomics, and physiology to elucidate how AR mutations drive tissue-specific metabolic reprogramming in key organs, including pancreatic β-cells, skeletal muscle, liver, and adipose tissue. Particular attention is given to a newly identified familial AR variant (c.2117A>G; p.Asn706Ser), which not only broadens the known mutational spectrum of AIS but also underscores the clinical importance of early metabolic risk screening in this population. We further examine how pubertal stage, hormone replacement therapy, and sex-specific signaling pathways interact to influence long-term metabolic outcomes. Lastly, we propose an integrative management framework that incorporates genetic diagnosis, endocrine surveillance, and personalized pharmacological strategies aimed at reducing the risk of type 2 diabetes mellitus and cardiometabolic complications in individuals with AIS. Distinct from previous AIS-centered reviews, this work integrates metabolic and endocrine perspectives into the traditional developmental paradigm, offering a more comprehensive understanding of disease risk and translational management.

PMID:41278448 | PMC:PMC12635778 | DOI:10.4239/wjd.v16.i11.112236

PERINATAL ORGANOPHOSPHATE FLAME RETARDANT EXPOSURE ALTERS ADULT HPA AXIS FUNCTION AND AVOIDANCE BEHAVIOR IN A SEX-SPECIFIC MANNER IN MICE - November 24, 2025

bioRxiv [Preprint]. 2025 Oct 14:2025.10.13.682090. doi: 10.1101/2025.10.13.682090.

ABSTRACT

Organophosphate flame retardants (OPFRs) are ubiquitous flame-retardant additives with endocrine-disrupting properties. Despite increasing evidence that OPFRs impact neurodevelopment, their effects on the neuroendocrine stress response remain poorly understood. To examine their long-term impact on stress regulation, we treated pregnant C57Bl/6J dams to a mixture of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), triphenyl phosphate (TPP), and tricresyl phosphate (TCP; 1 mg/kg each) from gestational day (GD) 7 through postnatal day (PND) 14. Adult offspring (8-9 weeks of age) were then challenged with acute stressors, including 1 h restraint or a 6-day acute variable stress (AVS) paradigm. Perinatal OPFR exposure produced persistent, sex-specific alterations in the hypothalamic-pituitary-adrenal (HPA) axis and stress-related neurocircuitry. Following 1 h restraint, OPFR-treated females showed heightened serum corticosterone. In addition, gene expression analysis revealed sex-dependent disruptions in key stress-regulatory pathways after OPFR treatment and 1 h restraint in the hypothalamus ( Crhr1, Crhr2, Ptpn5 ) and pituitary ( Crhr1, Pomc, Nr3c1 ). Females demonstrated more differences in adrenal gene expression related to steroidogenesis ( Mc2r, Cyp11b2 ) and catecholamine biosynthesis ( Dbh, Pnmt ), with OPFR-treated groups having blunted responses. OPFR AVS females displayed reduced corticosterone and downregulated Pacap/Pac1r expression in the bed nucleus of the stria terminalis (BNST), accompanied by increased behavioral avoidance and immobility. In males, OPFR exposure led to increased BNST Pacap and Pac1r , expression, along with hyperactivity and avoidance behaviors. Together, these findings demonstrate that early-life OPFR exposure induces lasting, sex-specific dysregulation of the HPA axis and associated stress circuits, highlighting OPFRs as developmental neuroendocrine disruptors with implications for mood and stress-related disorders.

PMID:41279807 | PMC:PMC12632834 | DOI:10.1101/2025.10.13.682090

In Vitro Fertilization Accelerates Female Reproductive Aging Through Early Ovarian Failure - November 24, 2025

bioRxiv [Preprint]. 2025 Oct 14:2025.10.13.682153. doi: 10.1101/2025.10.13.682153.

ABSTRACT

Reproductive aging is characterized by the progressive decline of reproductive function, with broad implications for overall health and longevity. Environmental factors, including assisted reproductive technologies (ART), can accelerate reproductive aging by promoting premature ovarian failure in females. In vitro fertilization (IVF), though widely used and generally considered safe, is associated with lasting effects on offspring health. Using a mouse model that closely approximates human IVF, we demonstrate that IVF accelerates reproductive aging in female offspring by inducing premature ovarian failure. IVF-conceived females exhibit altered ovarian function, disrupted endocrine profiles, and transcriptomic and epigenetic changes consistent with premature reproductive decline. These findings reveal long-term consequences of IVF on female reproductive health and highlight the need to understand how early-life interventions influence reproductive longevity.

PMID:41278955 | PMC:PMC12632968 | DOI:10.1101/2025.10.13.682153

Tetrabromobisphenol S (TBBPS) Causes Non-Negligible and Multigenerational Reproductive Toxicity in Zebrafish - November 24, 2025

Environ Sci Technol. 2025 Nov 24. doi: 10.1021/acs.est.5c07904. Online ahead of print.

ABSTRACT

Tetrabromobisphenol S (TBBPS) is one of the most extensively used brominated flame retardants detected in the environment. Despite its widespread presence, the effects of persistent environmental exposure to TBBPS on the reproductive system remain unclear, raising significant health concerns. Here, using the zebrafish (Danio rerio) model, we identified significant intergenerational endocrine disruption and reproductive toxicity induced by TBBPS after a life-cycle (150 days) of parental exposure to environmentally relevant concentrations of TBBPS (0.01, 0.1, 1, 10, and 100 μg/L). TBBPS interfered with hormone levels and the expression of genes within the hypothalamic-pituitary-gonadal (HPG) axis in both F0 males and females, leading to reduced embryo quality. The parental transmission of TBBPS also impacted the endocrine and reproductive systems of the F1 fish, including the increase of gonadotropin-releasing hormone 3 neuron numbers, changes in hormone levels, and a decrease in embryo numbers. F2 fish also displayed endocrine disruption, even in the absence of detectable TBBPS residues, evidenced by altered fertilization rates and vitellogenin levels. Together, our findings show that exposure to environmentally relevant concentrations of TBBPS can induce reproductive toxicity that persists across generations, weakening the endocrine system and early growth in offspring by disrupting the HPG axis. These data provide critical insight into the persistent health risks posed by TBBPS.

PMID:41283214 | DOI:10.1021/acs.est.5c07904

Association between environmental endocrine disruptors and autoimmune diseases: A systematic review and meta-analysis - November 24, 2025

iScience. 2025 Oct 21;28(11):113822. doi: 10.1016/j.isci.2025.113822. eCollection 2025 Nov 21.

ABSTRACT

Environmental endocrine disruptors (EDCs) affect the immune system and influence the development of autoimmune diseases (ADs). However, a comprehensive summary of the relationship between EDCs and ADs has not been developed. Consequently, we conducted a systematic review and meta-analysis of previous observational studies examining the association between exposure to EDCs and AD outcomes. We searched relevant literature published from January 2008 to the present, which ultimately included 19 studies. The synthesis of evidence demonstrated a positive association between AD risk and exposure to major EDC classes such as bisphenols (strongest association: OR = 2.38, 95% CI: 1.27-4.45), organochlorine pesticides, phthalates, and polycyclic aromatic hydrocarbons. This trend was not observed for polychlorinated biphenyls. These findings position EDC exposure as a potential risk factor for ADs, yet the mechanistic pathways require elucidation. Future high-quality longitudinal and experimental studies are essential to confirm these relationships and explore the underlying biology.

PMID:41280698 | PMC:PMC12637241 | DOI:10.1016/j.isci.2025.113822

The Biological Clock Influenced by Burnout, Hormonal Dysregulation and Circadian Misalignment: A Systematic Review - November 24, 2025

Clocks Sleep. 2025 Nov 3;7(4):63. doi: 10.3390/clockssleep7040063.

ABSTRACT

Burnout is increasingly recognized as both a psychosocial and a chronobiological disorder characterized by endocrine dysregulation and circadian disruption. It arises from chronic occupational stress and manifests through psychological, physical, and physiological symptoms. Although psychosocial determinants are well established, the biological and chronobiological mechanisms, particularly those involving cortisol and melatonin, remain less explored. This systematic review synthesizes current evidence on hormonal and circadian dysregulation in burnout and complements it with exploratory observational data from healthcare professionals. Peer-reviewed studies evaluating endocrine or circadian biomarkers in individuals with burnout were systematically reviewed. In addition, an exploratory observational analysis was carried out among 195 Romanian clinicians using an adapted Maslach Burnout Inventory. Morning salivary cortisol was measured once at 9 a.m. in a small subsample (n = 26) to provide preliminary physiological data. Because only a single time point was obtained, these values were interpreted as indicative of stress-related activation rather than circadian rhythm. Thirty-seven studies met the inclusion criteria. Across the literature, burnout was associated with altered HPA-axis activity, blunted diurnal cortisol variation, and irregular melatonin secretion related to shift work and disrupted sleep-wake cycles. Complementary exploratory data from our Romanian cohort indicated strong correlations between burnout severity, physical symptoms, and higher morning cortisol values among shift-working clinicians. These findings are preliminary and not representative of full circadian profiles. Burnout should be considered both a psychosocial and a systemic disorder influenced by endocrine and circadian dysregulation. Recognizing alterations in cortisol and melatonin as objective indicators may facilitate earlier detection and inform chronobiological interventions such as optimized scheduling, light exposure management, or melatonin therapy. The observational data presented here is preliminary and intended to generate hypotheses; future research should employ repeated cortisol sampling under controlled Zeitgeber conditions to confirm circadian associations.

PMID:41283312 | PMC:PMC12641836 | DOI:10.3390/clockssleep7040063

A Systematic Review: Migration of Chemical Compounds from Plastic Material Containers in Food and Pharmaceutical Fields - November 24, 2025

J Xenobiot. 2025 Nov 11;15(6):194. doi: 10.3390/jox15060194.

ABSTRACT

A systematic review was conducted on the migration of compounds from plastic containers in the food and pharmaceutical industries, using Web of Science databases and following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The protocol has been registered with the OSF registry, with the DOI 10.17605/OSF.10/UQ3T2. This review included only review articles in English published within the last fifteen years. Four reviewers independently screened titles and abstracts, discussing inclusion criteria. In this comprehensive evaluation of the information present in an Excel spreadsheet, a substantial number of records were discarded because they were not representative of the topic under study. Following the review process, a total of twenty-eight key records were selected, primarily focusing on migration in the food and pharmaceutical sectors. Of these, twenty-four addressed only food, just two addressed only pharmaceutical sector, and two covered both fields, highlighting limited information on migration in pharmaceuticals, cosmetics, and related products. The analysis emphasized the types of compounds studied, the analytical methods employed, the migration tests conducted, and the toxicity assessments undertaken. The most frequently assessed compounds included phthalates, endocrine disruptors like bisphenol A, and non-intentionally added substances (NIAS). Analytical methods used typically involved pre-treatment steps, such as liquid-liquid or solid-phase extraction, followed by gas or liquid chromatography, depending on compound volatility.

PMID:41283432 | PMC:PMC12641956 | DOI:10.3390/jox15060194

The golden touch: a comprehensive network pharmacology-guided review of synergy between curcumin and PARP inhibitors - November 24, 2025

Med Oncol. 2025 Nov 24;43(1):20. doi: 10.1007/s12032-025-03140-2.

ABSTRACT

Cancer remains the second leading cause of death globally. Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective targeted therapies, but their use is largely limited to BRCA-deficient cancers and is often hampered by resistance. This review explores combining PARPi with curcumin, a natural polyphenol, as an adjunct therapy. We reviewed literature and employed a network pharmacology approach to investigate shared molecular mechanisms. Curcumin induces DNA double-strand breaks while simultaneously impairing multiple repair pathways, including homologous recombination and non-homologous end joining. It also disrupts the ATR-CHK1 checkpoint. PARPi complements this by inhibiting base excision repair and trapping PARP-1 on DNA. This multi-pronged assault culminates in synthetic lethality and apoptosis. Our network pharmacology analysis identified 33 shared protein targets between curcumin and four FDA-approved PARPi. The resulting interaction network highlighted central hubs like ESR1 and SRC. Enriched pathways included PI3K/AKT signaling, VEGF signaling, and endocrine resistance. These findings suggest the combination targets not only DNA repair but also critical kinase signaling and tumor microenvironment pathways. This synergy offers a promising strategy to overcome resistance and expand PARPi to BRCA-proficient cancers. Significant challenges remain, including curcumin's low bioavailability and the complete absence of clinical trial data. Further research is essential to translate this preclinical potential.

PMID:41284132 | DOI:10.1007/s12032-025-03140-2

Vitamin C Mitigates Potassium Perchlorate Exposure-Induced Disruption of Spermatogenesis in Medaka - November 24, 2025

Environ Sci Technol. 2025 Nov 24. doi: 10.1021/acs.est.5c09514. Online ahead of print.

ABSTRACT

Endocrine-disrupting chemicals (EDC) can cause metabolic and reproductive impairments. It is essential to develop strategies to mitigate EDC-exposure-induced endocrine disruption. Potassium perchlorate (KClO₄), widely used in industrial and military applications, is an emerging environmental contaminant known to disrupt thyroid function. Its potential impact on male reproductive health remains underexplored. In this study, we investigated the testicular impairments caused by chronic KClO₄ exposure in medaka (Oryzias latipes) and examined whether KClO₄-induced testicular impairment can be mitigated. Adult male medaka were treated with 0.01 mg/L KClO₄, 10 mg/L KClO₄, and 10 mg/L KClO₄ plus vitamin C (3 mg/L) and vitamin C (3 mg/L) alone for 21 days. Fertilization percentage, histological examination, and transcriptomic alterations in the testis were determined. KClO₄ exposure decreased fertilization success and caused disorganization of seminiferous tubules and dysregulated spermatogenic genes in the testis. Transcriptomic analysis revealed substantial dysregulation of genes involved in cadherin and tubulin binding, chromatin remodeling, oxidative stress response, and germ cell development. Coadministration of vitamin C mitigated these effects by restoring testicular morphology, restoring fertilization rates, and partially normalizing gene expression changes disrupted by KClO₄ exposure. The present findings suggest that vitamin C provides protective effects against KClO₄-induced testicular toxicity and highlight the need for further exploration of antioxidant-based interventions to safeguard reproductive health from KClO₄ exposure.

PMID:41277501 | DOI:10.1021/acs.est.5c09514

Acute activation of Gq-signaling in islet macrophages inhibits β-cell insulin secretion through AMPK-sphingolipid axis - November 24, 2025

bioRxiv [Preprint]. 2025 Oct 30:2025.10.29.680858. doi: 10.1101/2025.10.29.680858.

ABSTRACT

Obesity-associated inflammation disrupts pancreatic β-cell function, but the immune-derived signals that directly regulate insulin secretion remain incompletely defined. Here, we identify myeloid Gq signaling as a critical immunometabolic node that links macrophage activation to β-cell dysfunction. For the first time, we employed a chemogenetic approach (DREADDs) to selectively and temporally activate Gq-coupled GPCR signaling in myeloid cells to examine its effect on islet function. Our findings reveal that acute Gq activation in islet-resident macrophages impaired glucose-stimulated insulin secretion, uncovering a previously unrecognized immune-endocrine axis. Conversely, myeloid-specific Gαq deletion improves systemic glucose homeostasis, underscoring the physiological relevance of this pathway. Mechanistic analysis revealed that Gq activation in macrophages stimulates AMPK signaling and drives the secretion of sphingolipids. These lipids suppress insulin secretion and introduce a new mechanism for immune-islet communication, extending beyond traditional cytokine-based models. We further identify the lipid-sensing receptor GPR18 as an upstream activator of the Gq-AMPK pathway in macrophages. GPR18 stimulation recapitulated the Gq-dependent sphingolipid secretion and β-cell inhibitory phenotype, which was abolished in myeloid Gαq-deficient mice. Collectively, these findings establish a mechanistic framework whereby macrophage Gq signaling integrates lipid sensing and metabolic stress to modulate β-cell function. This work reveals a previously unrecognized macrophage-β-cell communication axis with therapeutic potential for restoring insulin secretion in metabolic diseases such as obesity and type 2 diabetes.

PMID:41278909 | PMC:PMC12636625 | DOI:10.1101/2025.10.29.680858

A persistent luminescent lateral flow immunoassay for rapid and accurate detection of estradiol in real samples - November 24, 2025

Anal Chim Acta. 2026 Jan 1;1381:344813. doi: 10.1016/j.aca.2025.344813. Epub 2025 Oct 22.

ABSTRACT

BACKGROUND: The demand for highly sensitive and reliable environmental monitoring methods has led to extensive research on new rapid detection technologies. Fluorescent immunochromatographic test strips are widely used for the detection of endocrine disruptors due to their advantages of rapid response, high sensitivity, and good selectivity. However, most current lateral flow immunoassay (LFIA) use excitation-dependent organic fluorescent molecules or quantum dots as signal label, which are susceptible to interference from background fluorescence in complex samples, thereby reducing their accuracy and sensitivity in real sample detection.

RESULTS: In this work, a novel immunochromatographic test strip was constructed for the anti-interference detection of endocrine disruptors in complex samples using persistent luminescent nanomaterials as signal units and antibodies for specific recognition of target molecule. The synthesized Zn₂GeO₄:Mn (ZGO:Mn) persistent luminescent nanomaterials possessed bright green luminescence after excitation turn off, allowing eliminate sample autofluorescence interference. As the proof-of-concept of this novel LFIA, estradiol (E2) was chosen as a model system to be investigated. After optimization, the persistent luminescent LFIA exhibited a good linear range from 0 to 15 μg/L with the limit of detection of 507 ng/L for E2, which are below the concentration range of E2 in most municipal wastewater systems. In addition, the persistent luminescent LFIA had strong specificity and high accuracy for E2 detection in water samples and milk samples.

SIGNIFICANCE: This study introduces a persistent luminescent lateral flow immunoassay for E2 detection with minimized background interference. Significantly, this persistent luminescent LFIA has better detection performance than traditional fluorescent LFIA, showing tremendous potential for determination and control of E2 in real samples.

PMID:41285541 | DOI:10.1016/j.aca.2025.344813

The placental transcriptome serves as a mechanistic link between prenatal phthalate exposure and placental efficiency - November 23, 2025

Environ Int. 2025 Nov 20;206:109949. doi: 10.1016/j.envint.2025.109949. Online ahead of print.

ABSTRACT

Prenatal exposure to phthalates, pervasive endocrine-disrupting chemicals, has been linked to child health outcomes, including prematurity and low birthweight. Placental transcriptomics data can reveal mechanisms by which environmental toxicants alter placental and fetal growth. This study aims to investigate the placental transcriptome as a mediator between prenatal maternal urinary phthalate metabolites and placental efficiency. We identified significant associations between maternal urinary concentrations of phthalate metabolites and the placental transcriptome (132 genes and 27 gene modules). Placental efficiency was modeled as the ratio of birthweight to placental weight (BW:PW) and as birthweight adjusted for placental weight (BW_adj) and was also significantly associated with the placental transcriptome (460 genes and 11 gene modules). 4 genes and 9 gene modules exhibited significant mediation of the relationship between maternal urinary concentrations of phthalate metabolites and placental efficiency measures. These genes were involved in syncytialization, metabolism, DNA damage and cellular senescence, and steroid biosynthesis-processes essential to fetal growth and development because of the placenta's role in nutrient supply, hormone production, and detoxification. These findings suggest a key mediating role of the placental transcriptome in toxicological mechanisms by which phthalates may disrupt fetal growth.

PMID:41275761 | DOI:10.1016/j.envint.2025.109949

Association of in utero exposure to phthalate and DINCH metabolites with placental DNA methylation - November 23, 2025

Environ Int. 2025 Nov 19;206:109946. doi: 10.1016/j.envint.2025.109946. Online ahead of print.

ABSTRACT

Phthalates and DINCH are non-persistent chemicals widely used in consumer products. In utero exposure to these compounds has been linked to adverse reproductive and long-term health outcomes, potentially through epigenetic changes in the placenta. This study investigated associations between maternal phthalate and DINCH metabolite levels and placental DNA methylation in 469 mother-child pairs from the Barcelona Life Study Cohort (BiSC). Fifteen phthalate and two DINCH metabolites were measured in pooled maternal urine samples collected at 19 and 35 weeks of gestation using liquid chromatography-tandem mass spectrometry (LC-MS/MS. Placental DNA methylation was assessed using the Illumina EPIC array. We applied robust linear regression models to test associations between single exposures at 19 weeks, 35 weeks, and whole pregnancy (average of the two time points), with each CpG site. In secondary analyses, quantile g-computation was used to test associations between exposure mixtures and suggestive CpGs (p-value < 1E-05). We identified 38 Bonferroni significant associations in the single exposure models (p-value < 1E-07)- 24 at 19 weeks, 8 at 35 weeks and 6 for the whole pregnancy period. Suggestive CpGs (p-value < 1E-05) were annotated to genes involved in metabolic, immune and vascular pathways, steroid biosynthesis, and sex hormone signaling. Sex-stratified analyses revealed 49 female-specific and 42 male-specific associations, most of which were identified at a single time point. Mixture analyses revealed 20 significant associations, all consistent in direction with the single-metabolite models. These results suggest that prenatal exposure to phthalates and DINCH may contribute to placental epigenetic alterations supporting a role for endocrine disruption, metabolism, and vascular and immune modulation in mediating their effects.

PMID:41275763 | DOI:10.1016/j.envint.2025.109946

Seasonal testicular morphometry of European brown bears in relation to pollutants - November 23, 2025

Environ Res. 2025 Nov 21;289:123383. doi: 10.1016/j.envres.2025.123383. Online ahead of print.

ABSTRACT

Inorganic and organic pollutants are capable of affecting the reproductive health of both animals and humans. The resulting pollutant-induced phenotype disorders have been rarely studied in wildlife males that commonly associate with diminished sperm quality leading to subfertility. We investigated testicular morphometry in Dinara-Pindos population of protected European brown bears (Ursus arctos) in relation to metal(loid)s (N = 44), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) (N = 27), while controlling for age, body condition, and season. The principal approximating generalized linear models included following predictors of testicular mass and size: age (greater mass and larger size in adults than in subadults), toxic As (↓), Pb (↑), and Hg (↓), and essential Mn (↓), Se (↑), and Cu (↓) levels in the testes and/or epididymides. When organic pollutants were included in models explaining testicular mass and size variation instead of metal(loid)s, subcutaneous fat levels of PCB-118 (↑) and PCB-180 (↓), age (greater mass and larger size in adults) and season (higher in breeding than in non-breeding season) showed significant contribution. Higher mass and size of testes were found in breeding season (Mar-Apr) compared to non-breeding season (Oct). Metal(loid) concentrations, reported for the first time in ursid testicular and epididymal tissue, add to very scarce body of data from other wild terrestrial mammals. Associations between morphometric indices of male reproductive organs and certain endocrine-disrupting pollutants highlight potential toxicological relevance for wildlife chronically exposed to diffuse, global pollution sources.

PMID:41276004 | DOI:10.1016/j.envres.2025.123383

Molecular mechanisms of p-phenylenediaminequinone toxicity in male infertility: a network toxicology and docking study - November 23, 2025

Environ Int. 2025 Nov 21;206:109947. doi: 10.1016/j.envint.2025.109947. Online ahead of print.

ABSTRACT

p-Phenylenediaminequinones (PPD-Qs) are oxidized derivatives of common p-phenylenediamine (PPD) antioxidants. These compounds have emerged as persistent environmental toxicants detected across diverse ecological matrices and human samples. Despite their widespread presence, the mechanistic links between PPD-Qs and male reproductive dysfunction remain largely unexplored. In this study, we employed an integrated approach combining network toxicology and molecular docking to systematically investigate the molecular mechanisms underlying the association of five PPD-Qs with male infertility and its principal subtypes: hypogonadotropic hypogonadism (HH), hyperprolactinemia (HPL), and immunological infertility (IMI). Our analysis identified 479 PPD-Q-related targets and 3142 male infertility-related targets, with 230 overlapping targets indicating potential interactions. Protein-protein interaction network analysis revealed 15 core targets associated with male infertility, while subtype-specific analyses identified 22, 13, and 66 core targets for HH, HPL, and IMI, respectively. GO and KEGG enrichment analyses delineated three primary mechanistic pathways: (1) disruption of reproductive endocrine homeostasis through estrogen, GnRH, and prolactin signaling; (2) dysregulation of cellular signaling cascades, including the MAPK and PI3K-AKT pathways; and (3) modulation of immune function and oxidative stress responses. Notably, AKT1 and ESR1 emerged as conserved targets across all conditions. Molecular docking studies demonstrated strong binding affinity (-6.6 to -9.8 kcal/mol) between PPD-Qs and core targets, with DTPD-Q exhibiting the highest affinity. Our findings establish AKT1 and ESR1 as conserved molecular targets across male infertility and its subtypes, supported by the strong computational binding affinities. By integrating network toxicology, this study extends previous research on individual PPD-Qs, demonstrating their capacity to disrupt multiple pathways involving endocrine regulation, immune function, and oxidative stress responses. These insights provide a mechanistic foundation for future environmental monitoring and the development of targeted intervention strategies.

PMID:41275765 | DOI:10.1016/j.envint.2025.109947

Capsaicin alleviates DEHP-induced testicular dysfunction by suppressing oxidative stress in mice - November 23, 2025

Toxicol Appl Pharmacol. 2025 Nov 21;506:117655. doi: 10.1016/j.taap.2025.117655. Online ahead of print.

ABSTRACT

Di(2-ethylhexyl) phthalate (DEHP) is a widespread environmental endocrine disruptor known to impair testicular function. Capsaicin, the bioactive compound in chili peppers, has not been thoroughly explored for its protective effects against DEHP-induced testicular damage. In this study, male C57BL/6 mice were divided into control, DEHP-exposed (200 mg/kg/day orally for 6 weeks), and DEHP-exposed with varying doses of capsaicin (5, 10, and 20 mg/kg/day orally for 6 weeks). Leydig and Sertoli cells were cultured in vitro with DEHP or capsaicin (0, 25, 50, and 100 μM). Chronic DEHP exposure impaired testicular development, leading to morphological abnormalities and reduced sperm quality, which were largely restored by capsaicin treatment. Both in vivo and in vitro assays revealed that capsaicin modulated the BAX/BCL2 ratio and inhibited testicular apoptosis. Additionally, capsaicin restored DEHP-induced suppression of testosterone biosynthesis in Leydig cells and maintained the integrity of the blood-testis barrier in Sertoli cells. Mechanistically, these protective effects were likely due to the antioxidant properties of capsaicin. In conclusion, our findings suggest that capsaicin may serve as a promising therapeutic agent for mitigating DEHP-induced testicular dysfunction, offering valuable insights for potential clinical applications.

PMID:41276025 | DOI:10.1016/j.taap.2025.117655