Endocrine Disruption

Phenol biomarker concentrations in human ovarian follicular fluid and the associations with in-vitro fertilization outcomes - July 5, 2025

Int J Hyg Environ Health. 2025 Jul 4;268:114617. doi: 10.1016/j.ijheh.2025.114617. Online ahead of print.

ABSTRACT

BACKGROUND: Phenols are a family of short-lived endocrine disrupting chemicals found in a wide range of products and have drawn significant attention because of widespread human exposure and their potential adverse effects on reproductive health. Phenols have been widely detected in several human bodily fluids, particularly in urine and blood. However, there is limited data on phenols in human ovarian follicular fluid (FF). In addition, studies suggest associations between exposure to bisphenols and measures of infertility in humans. Nevertheless, the association of FF concentrations of bisphenols and female fertility has not been investigated.

OBJECTIVES: To quantify phenols in human ovarian FF, investigate correlations of phenol concentrations between FF and urine, evaluate trends over time, and explore any associations between FF concentrations of phenols and in-vitro fertilization (IVF) outcomes.

METHODS: This analysis includes 143 women who enrolled in the Environment and Reproductive Health (EARTH) Study and underwent one IVF cycle between 2009 and 2015, with available, FF, urine and reproductive outcome data. FF concentrations of 2,4-dichloro-phenol (2,4DCP), 2,5-dichloro-phenol (2,5DCP), methyl-paraben (MPB), ethyl-paraben (EPB), propyl-paraben (PPB), butyl-paraben (BPB), bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), benzophenone-3 (BP3), triclosan (TCS) and triclorocarban (TCC) were quantified by isotope dilution tandem mass spectrometry. Generalized linear models were used to explore the associations between FF concentrations of bisphenols (in tertiles or dichotomized) and IVF outcomes, adjusting for confounders.

RESULTS: Detection rates varied from high (79-95 %) for MPB, PPB and BPS, to moderate (44-65 %) for BPA, BP3 and TCS, to low (1-34 %) for 2,4DCP, 2,5DCP, EPB, BPB, BPF, TCC. Correlations between FF and urine were strong for BP3 (r = 0.86), moderate for MPB (r = 0.64) and PBP (r = 0.63), and weak for BPS (r = 0.21) and BPA (r = 0.12). FF BPA concentrations significantly decreased over time, whereas FF BPS concentrations increased. Most of the examined FF phenol biomarker concentrations were not related to early IVF outcomes (endometrial thickness, total and mature (MII) oocyte yield, fertilization rates). However, significant associations between PPB and endometrial thickness, and between BP3 and MII oocyte yield were noted, without these findings translating in any effects observed on pregnancy outcomes (implantation, clinical pregnancy and live birth).

CONCLUSIONS: We observed that most phenols were detected in FF and there were some correlations with urinary concentrations. We confirmed in FF that phenols such as BPA may be declining, while exposure to new replacements such as BPS are increasing. However, no overall associations were observed for the examined FF phenol biomarker concentrations with early IVF outcomes and pregnancy outcomes. Further research is needed to examine the potential associations of these phenols in FF, especially the newer ones that are on the rise.

PMID:40617121 | DOI:10.1016/j.ijheh.2025.114617

Comparative effectiveness of equol on estrogen and androgen disruption and metabolic parameters in adult male Sprague-Dawley rats - July 5, 2025

Ecotoxicol Environ Saf. 2025 Jul 4;302:118606. doi: 10.1016/j.ecoenv.2025.118606. Online ahead of print.

ABSTRACT

Previous research has investigated the biological activities of equol (EQ), but no experiments have been carried out with positive estrogenic and anti-androgenic animal models to disclose the accurate biological actions of EQ in male rats. This research aimed to investigate the mechanisms of EQ action compared to estradiol valerate (E2V) and anti-androgenic drug flutamide (FLUT) on pituitary-testicular (PT) axis hormonal profiles, metabolic parameters, histopathological and histomorphological changes in male rat pituitary and reproductive organs, and fertility. Three-month-old male Sprague-Dawley rats (n = 12/group) were treated for five days with either EQ (0.25, 2.5, 30, 100, 250 mg/kg/day), E2V (0.6 mg/kg/day), or FLUT (100 mg/kg/day). Key findings revealed that EQ exerted estrogen agonism on PT axis and lipid parameters, resulting in upregulation of pituitary estrogen receptor (ER)-alpha protein expression and decreased levels of plasma luteinizing hormone (LH), testosterone (T), total cholesterol (TC), and lipoproteins, whereas FLUT had opposite effects. Underlying histopathological mechanisms involved in EQ and E2V versus FLUT actions on (i) reductions of seminal vesicle weight and epithelial thickness, tubular/acini, epithelial and luminal areas of prostate and epididymis, and vas deferens, (ii) changes in the frequency of seminiferous epithelial cycle stages, (iii) occurrence of germ cell debris in epididymal tubule, and (iv) enlargement of prostatic stroma, were different due to opposing changes in LH/T profiles, Leydig cell morphology, and relative weights of epididymides and vas deferens. EQ treatment did not result in detectable changes in pituitary cell nuclear size, hepatic injury, and infertility rate, suggesting the potential of EQ as a safe pituitary-ER alpha modulator for promoting beneficial effects on male rat reproductive endocrine and hepatic tissues.

PMID:40617223 | DOI:10.1016/j.ecoenv.2025.118606

Effects of environmental toxicant exposures on oxytocin and vasopressin systems in the developing brain: Factors imparting risk and resilience - July 5, 2025

Behav Brain Res. 2025 Jul 3:115723. doi: 10.1016/j.bbr.2025.115723. Online ahead of print.

ABSTRACT

Environmental toxicants are increasingly prevalent worldwide and associated with numerous neurodevelopmental and psychiatric health outcomes. Exposure to these toxicants, particularly during gestation and the early postnatal period, alters maternal and offspring stress responses, inflammation, and behavioral outcomes. Oxytocin (OT) and arginine vasopressin (AVP) are highly conserved neuropeptides with myriad roles in the regulation of social behavior, stress responses, and more. While developmental stress is well known to impact OT and AVP systems, a growing body of literature suggests that early-life exposure to toxicants also impacts OT and AVP system development. Here we review the evidence demonstrating that perinatal exposures to environmental toxicants program developmental trajectories of the OT and AVP systems. Perinatal exposure to flame retardants, pesticides, plastics, and air pollution induces a variety of changes to OT and AVP systems in the brain, affecting the neuropeptides themselves as well as their primary central receptors, the oxytocin receptor (OTR) and the vasopressin receptor 1a (V1aR), respectively. Next, we discuss two biological mechanisms of action that may underlie the effects of toxicant exposure on OT and AVP: endocrine disruption and maternal immune activation. Finally, we explore key factors that promote either risk or resilience to toxicant exposures, including psychosocial experience, sex, the gut microbiome, and dosage/timing of exposure. Cumulatively, the literature reviewed suggests that preventing psychosocial stress to mothers during the perinatal period while promoting positive psychosocial experiences may lessen the impact of toxicants on offspring outcomes. Furthermore, the gut microbiome may be an important intermediary, and therefore target for intervention, between toxicant exposures and OT and AVP systems in the brain.

PMID:40617300 | DOI:10.1016/j.bbr.2025.115723

Extracellular matrix dysregulation in PCOS: pathogenesis, therapeutic strategies, and innovative technologies - July 5, 2025

J Biol Eng. 2025 Jul 5;19(1):61. doi: 10.1186/s13036-025-00533-9.

ABSTRACT

Polycystic ovary syndrome (PCOS), the most common endocrine disease in women of reproductive age, severely impacts female fertility due to chronic anovulation and currently lacks effective clinical treatment strategies. The extracellular matrix (ECM) is a three-dimensional, non-cellular framework comprising molecules such as collagens, elastin, and laminin, which support the ovarian structure and provide extracellular signals to cells. Changes in ECM localization and composition can disturb local biochemical pathways, impair folliculogenesis, and reduce the fertility of women. This paper explores innovative therapeutic approaches for PCOS by investigating the mechanisms underlying PCOS pathogenesis due to ECM dysregulation. This includes ECM deposition-induced inflammation and fibrosis, impaired ECM degradation, altered mechanical forces in ECM remodeling, and disrupted interactions between granulosa cells and the ECM. In the second part, we present therapeutic strategies informed by these pathogenic mechanisms, integrating insights from basic and clinical research. More importantly, this paper introduces innovative therapies for POCS that regulate ECM. These therapeutic strategies represent future development directions. In the final section, we summarize the advantages, potential challenges, and prospects of ECM-based treatments for improving fertility in PCOS. Overall, this review underscores the emerging significance of ECM-targeted interventions in unraveling PCOS pathophysiology and paves the way for the development of more precise and effective fertility-preserving therapies.

PMID:40618169 | DOI:10.1186/s13036-025-00533-9

<em>In vitro</em> effects of environmentally relevant concentrations of nonylphenol and selected pyrethroid metabolites on a mouse Sertoli cell line (TM4) - July 4, 2025

Toxicol Mech Methods. 2025 Jul 4:1-13. doi: 10.1080/15376516.2025.2528100. Online ahead of print.

ABSTRACT

Advances in the chemical industry and increased environmental pollution have contributed to declining reproductive health. Many pollutants act as endocrine-disrupting chemicals (EDCs), with (anti-)estrogenic and (anti-)androgenic properties that disrupt hormonal balance and contribute to male reproductive dysfunction. Mouse Sertoli cells, which closely resemble human Sertoli cells, are targets for various environmental contaminants, making the cell line an ideal model for male reproductive toxicological studies. Sertoli cells (TM4) were exposed to environmentally relevant concentrations of EDCs, including cypermethrin, deltamethrin, rac-trans permethrinic acid, 3-phenoxybenzoic acid and para-nonylphenol (p-NP), for 24 hours in vitro. Cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, oxidative stress via an intracellular total reactive oxygen species (ROS) activity assay kit, and morphological changes via hematoxylin & eosin staining. The MTT assay revealed a moderate decrease (approximately 20% cell death) in cell viability. ROS levels were significantly higher in EDC-treated cells than in controls, with small effect sizes confirmed through Cohen's d analysis. Morphological changes, including membrane elongation, cytoplasmic vesicles, and reduced cell density, were most pronounced in p-NP-exposed cells. These findings suggest that exposure to pyrethroids and nonylphenol may induce toxicity in mouse Sertoli cells.

PMID:40611667 | DOI:10.1080/15376516.2025.2528100

Microplastics: A threat to Fetoplacental unit and Reproductive systems - July 4, 2025

Toxicol Rep. 2025 Jan 30;14:101938. doi: 10.1016/j.toxrep.2025.101938. eCollection 2025 Jun.

ABSTRACT

Plastic pollution has become a pressing global environmental and public health challenge, raising significant concerns about its potential effects on human health. While extensive research has been conducted on micro- and nanoplastics (MNPs), there remains a critical gap in understanding how these plastic particles traverse the maternal-fetal interface and contribute to reproductive anomalies. This review aims to address this knowledge gap by examining the effects of MNPs on the fetoplacental unit, a vital structure that serves as the interface between the mother and fetus during pregnancy, as well as on the broader reproductive system. Traditionally viewed as a protective barrier safeguarding the fetus, emerging evidence suggests that the placenta may also act as a site for the accumulation of plastic particles, thereby compromising its function. A literature search was conducted using a combination of keywords on Google Scholar and PubMed including 'plastic particles affect the fetoplacental unit', 'how plastic particles traverse the maternal-fetal contact', and reproductive abnormalities induced by micro/nano-plastics'. Key studies show that plastic particles can traverse the maternal-fetal interface, potentially exposing developing fetuses to various harmful chemicals present in plastics, such as endocrine disruptors and persistent organic pollutants. Once in contact with the fetoplacental unit, these particles may trigger inflammatory responses, oxidative stress, and even epigenetic modifications. They also bioaccumulate in testes, altering spermatogenesis, spermatozoa morphology, testosterone production, body weights, and inflammation as reported in mice. Such disruptions can increase the risk of developmental and reproductive disorders in the fetus, suggesting that exposure to plastic particles may carry long-term health implications. Further studies highlight the particular vulnerability of the fetoplacental unit to plastic particles. The placenta has limited detoxifying capabilities and unique immunological regulation, making it especially sensitive to foreign particles. Identifying critical windows of susceptibility during pregnancy is germane, as exposure to plastic particles during these periods could have heightened effects on fetal development. This growing concern underscores the urgent need for comprehensive research into the mechanisms through which plastic particles impact the fetoplacental unit. Additionally, this review calls for stronger measures to mitigate plastic pollution and recommends health strategies aimed at protecting future generations from potential harm. It synthesizes recent findings on the ways in which these particles influence the fetoplacental unit and the broader reproductive system.

PMID:40612654 | PMC:PMC12223432 | DOI:10.1016/j.toxrep.2025.101938

Advances in the interrelated nature of vaginal microecology, HPV infection, and cervical lesions - July 4, 2025

Front Cell Infect Microbiol. 2025 Jun 19;15:1608195. doi: 10.3389/fcimb.2025.1608195. eCollection 2025.

ABSTRACT

Vaginal microecology serves as a crucial defense mechanism in women's reproductive health. It encompasses vaginal anatomy, microbial flora, endocrine regulation, and immune responses. Lactobacillus species dominate this ecosystem, maintaining a dynamic balance essential for vaginal health. Studies have highlighted a strong association between vaginal microecology, human papillomavirus (HPV) infection, and cervical lesions. A well-balanced vaginal microenvironment enhances mucosal barriers and immune function, aiding in HPV prevention and clearance. Conversely, disruptions in vaginal microecology compromise these defenses, increasing susceptibility to HPV infection. Persistent high-risk HPV (HR-HPV) infections are key contributors to cervical lesions and may further destabilize the vaginal microbiota(VMB). Additionally, cervical lesion progression is influenced by local immune responses, with HPV infection potentially accelerating disease development by suppressing cervical immunity. This review explores the intricate association between vaginal microecology, HPV infection, and cervical lesions, offering insights into early diagnosis, prevention, and treatment strategies.

PMID:40612393 | PMC:PMC12222100 | DOI:10.3389/fcimb.2025.1608195

Legacy and current-use contaminants in pacific chinook salmon (oncorhynchus tshawytscha) stocks and their contribution to Resident killer whale (orcinus orca) contaminant burdens - July 4, 2025

Environ Toxicol Chem. 2025 Jul 4:vgaf166. doi: 10.1093/etojnl/vgaf166. Online ahead of print.

ABSTRACT

The Endangered Southern Resident killer whales (SRKW, Orcinus orca) face significant threats including reduced abundance and quality of their primary prey (Chinook salmon, Oncorhynchus tshawytscha) and high levels of endocrine disrupting contaminants while experiencing a decrease in population growth over the past several decades. The sympatric Northern Resident killer whales (NRKW) also primarily consume Chinook but have lower contaminant burdens and have experienced consistent population growth for nearly five decades. This study characterized concentrations of 19 legacy and current-use contaminants in priority Chinook stocks/groups consumed by SRKWs and NRKWs, calculated Chinook contaminant body burden, estimated daily contaminant intake (EDI) from Chinook salmon in SRKW diet across seasons, and compared Chinook salmon related EDI between SRKW and NRKW during the months of May to October. Shelf Resident Chinook had higher mean muscle ∑contaminant19 concentrations and mean ∑contaminant19 body burdens than Columbia (4.9- and 2.6-fold, respectively) and Far North/Offshore Chinook (5.7- and 2.1-fold, respectively). This resulted in a disproportionately higher contaminant intake by SRKW from Shelf Resident Chinook throughout the year relative to Far North/Offshore Chinook. From May to October, an average SRKW consumed approximately 15.4% more Shelf Resident Chinook a day than an average NRKW resulting in a 5.3-fold higher EDI from Shelf Resident Chinook and an overall 1.62-fold higher EDI (1410 μg ∑contaminants19/day) from all three Chinook groups compared to NRKW EDI (869 μg ∑contaminants19/day). Results provide an updated characterization of contaminant exposure for NRKWs and SRKWs, insights into the current levels of priority contaminants in Chinook salmon, and an explanation as to why SRKW have higher contaminant loads than NRKW. Recovering at-risk wild Chinook salmon populations that have a more offshore rearing distribution and lower contaminant body burdens (ie, Columbia and Far North/Offshore Chinook stocks) should be a top priority to ensure the recovery of SRKW.

PMID:40613683 | DOI:10.1093/etojnl/vgaf166

Endocrine-disrupting chemicals (EDCs) and epigenetic regulation in embryonic development: Mechanisms, impacts, and emerging trends - July 4, 2025

Toxicol Rep. 2024 Dec 27;14:101885. doi: 10.1016/j.toxrep.2024.101885. eCollection 2025 Jun.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are prevalent ecological pollutants that interfere with hormonal systems and pose serious health risks to the public, especially during critical developmental windows. Well-known EDCs, such as bisphenol A (BPA) and phthalates, can alter gene regulation and induce epigenetic modifications that worsen reproductive and developmental disorders. This review explores the intricate relationships that exist among epigenetic mechanisms, EDCs, and embryonic development, with a focus on significant modifications such as DNA methylation, histone modifications, and noncoding RNA dynamics that are critical for cellular differentiation. We review the possible health implications of EDC-induced epigenetic changes, focusing on how they could increase susceptibility to diseases. In addition, we provide a critical review of the available treatments aimed at reversing these epigenetic changes and highlight the groundbreaking technologies of high-throughput sequencing and CRISPR-based epigenome editing that are redefining the understanding of EDC effects. This thorough analysis highlights the necessity of efficient regulations that lower EDC exposure as well as the possibility of customized preventative measures to ensure developmental safety.

PMID:40612660 | PMC:PMC12223400 | DOI:10.1016/j.toxrep.2024.101885

Oxygenated Liquid Organic Hydrogen Carrier (oxo-LOHC) systems: The biodegradation and endocrine disrupting potential of oxo-LOHCs, intermediates and transformation products - July 4, 2025

J Hazard Mater. 2025 Jun 22;495:139030. doi: 10.1016/j.jhazmat.2025.139030. Online ahead of print.

ABSTRACT

Oxo-Liquid Organic Hydrogen Carrier (oxo-LOHC) systems have come to prominence because of their high hydrogen storage capacity (≥ 6.3 wt%) and favourable thermodynamic properties (i.e. low dehydrogenation temperature). Given the potential scale of use of oxo-LOHCs as energy carriers, the environmental impact of these systems needs to be carefully considered. We investigated the biodegradability of twelve oxo-LOHC compounds involved in three hydrogen carrier systems. The ultimate biodegradation test demonstrated that the acetophenone-based LOHC system (H0-ACP/H8-ACP) is readily biodegradable as both compounds exhibited mineralisation above 60 % within a 10-day window (from 10 % to 60 %). In contrast, 14H-4-MBP showed potential for persistence, exhibiting less than 20 % biodegradation in both ultimate and primary biodegradation tests. H0-2-MBP exhibited low levels of primary degradation (<50 %) at both low and high initial concentrations The other oxo-LOHC compounds tested were found to be inherently biodegradable, with an average primary biodegradation rate of over 50 %, at least at one test concentration. Our findings suggest that hydrogenation of the phenyl ring and methyl substitution on the ring may decrease biodegradability. The analysis of transformation products (TPs) showed that oxo-LOHC compounds initially undergo (de)hydrogenation and/or hydroxylation, with the latter reaction potentially enhancing the estrogenic and antiestrogenic activities. Based on the 43 TPs identified, we propose biodegradation pathways for four compounds. The use of BIOWIN models generally offers a reliable estimation for the biodegradability of oxo-LOHC compounds. This study improves our understanding of biodegradation and provides guidance on the selection of inherently benign chemicals for use in LOHC systems and beyond.

PMID:40614419 | DOI:10.1016/j.jhazmat.2025.139030

The impact of bisphenol A and its analogs on female reproductive health - July 4, 2025

Reprod Biol. 2025 Jul 3;25(3):101028. doi: 10.1016/j.repbio.2025.101028. Online ahead of print.

ABSTRACT

The number of pollutants stemming from anthropogenic chemicals is increasing every year. Some of them act similarly to hormones and are referred to as endocrine-disrupting chemicals or endocrine disruptors. In this group, bisphenol A (BPA) is well characterized as a xenoestrogen and is known to affect human health. BPA is crucial to the production of plastic, a material that has revolutionized and facilitated daily life. Nevertheless, the use of BPA is currently being limited, and consequently, new BPA analogs are under development. However, both BPA and its analogs can be released into the environment during their manufacturing process and daily usage. In conjunction with the escalating demand for plastics and the prolonged persistence of plastic waste, it poses a substantial threat to human health. In this article, we concentrate on the influence of BPA and its most common analogs (bisphenol S, bisphenol F, bisphenol AF, bisphenol Z, bisphenol P, bisphenol AP, bisphenol B) on female reproductive health. We reviewed the existing epidemiological data (or in the absence of it, data obtained from animal and in vitro models) on their impact on hormone levels, oocyte yield, oocyte and embryo quality, implantation and pregnancy success, polycystic ovary syndrome, and endometriosis. We also discuss metabolism of bisphenols, their mechanism of action and impact on cellular physiology, as well as current regulations on their use. Our comprehensive review reveals that, despite existing discrepancies, a substantial body of evidence suggests that bisphenols influence female reproductive health. This underscores the urgent need for future regulatory measures to limit and regulate the use of bisphenols.

PMID:40614486 | DOI:10.1016/j.repbio.2025.101028

Bisphenol A Exposure and Behavioral Outcomes in Children: A Systematic Review and Meta-Analysis of Evidence Limited to the BASC Assessment Tool - July 4, 2025

Neurosci Biobehav Rev. 2025 Jul 2:106274. doi: 10.1016/j.neubiorev.2025.106274. Online ahead of print.

ABSTRACT

BACKGROUND: The growing concern about exposure to endocrine disrupting chemicals (EDCs), and their effects on human health, especially the possible neurobehavioral effects in children, makes a review of the scientific evidence on the subject important. The study conducts a systematic review and applies meta-analysis to determine whether there is a relationship between bisphenol exposure and behavioral development in children, as measured by the Behavioral Assessment System for Children (BASC).

METHODS: In June and July 2024, Scopus, Web of Science, and Medline with PubMed were the databases used to search for studies within the scope of this study. A total of 562 articles were found, of which 59 were analyzed; finally, 13 studies met the inclusion criteria for systematic review and 7 for the meta-analysis. The scales measured in the different studies have been aggression, attention, hyperactivity, depression, anxiety and somatization; behavioral indices (behavioral symptom index, externalizing and internalizing behaviors) were also analyzed.

RESULTS: Most of the studies found no significant associations and no consistency in the results obtained. The heterogeneity in the design of the studies made it impossible to generate conclusive results in the application of meta-analysis.

DISCUSSION: There is a sex-based differentiation in the behavioral effects associated with bisphenol exposure, as bisphenols affect boys and girls differently, potentially through mechanisms involving estrogen receptors, among other biological pathways.

CONCLUSIONS: Our study highlights the need to improve and homogenize the design and results of epidemiological studies to extract data effectively. More results are needed to be able to draw conclusions.

PMID:40614948 | DOI:10.1016/j.neubiorev.2025.106274

Microplastics: A threat to Fetoplacental unit and Reproductive systems - July 4, 2025

Toxicol Rep. 2025 Jan 30;14:101938. doi: 10.1016/j.toxrep.2025.101938. eCollection 2025 Jun.

ABSTRACT

PMID:40612654 | PMC:PMC12223432 | DOI:10.1016/j.toxrep.2025.101938

Thymol alleviates silica dioxide nanoparticle-induced reproductive performance toxicity via antioxidant and anti-inflammatory mechanisms in male rats - July 4, 2025

Sci Rep. 2025 Jul 4;15(1):23913. doi: 10.1038/s41598-025-07769-x.

ABSTRACT

Nanoparticles (NPs) have gained increasing attention due to their unique physicochemical properties and broad applications. However, concerns about their potential toxicity, particularly reproductive toxicity, have emerged. Silica dioxide nanoparticles (SiO₂-NPs) are among the most commonly used NPs and have been linked to adverse effects on male reproductive health. This study aimed to evaluate the potential ameliorative effect of thymol, a natural monoterpene phenol with antioxidant and anti-inflammatory properties, against SiO₂-NPs-induced reproductive toxicity in male rats. Twenty-four adult male Sprague-Dawley rats were randomly assigned to four groups: control, SiO₂-NPs-treated (10 mg/kg body weight, intraperitoneally), thymol-treated (30 mg/kg body weight, orally), and SiO₂-NPs + thymol co-treated. Treatments were administered daily for 56 days. Male reproductive performance was evaluated through sexual behavior assessment, sperm characteristics, reproductive hormone levels, oxidative stress markers, inflammatory biomarkers, gene expression analysis, and histopathological examination of testicular tissue. Results revealed that SiO₂-NPs significantly impaired reproductive performance, indicated by reduced sperm motility, viability, and count, along with increased sperm abnormalities. Thymol co-administration significantly restored testosterone levels and partially normalized elevated LH and FSH levels caused by SiO₂-NPs, indicating endocrine protection. Moreover, SiO₂-NPs induced oxidative stress, elevated pro-inflammatory cytokines (TNF-α and IL-6), and disrupted the expression of key genes associated with oxidative stress response (NRF2), apoptosis (BAX, BCL-2), steroidogenesis (STAR, CYP11A1), and spermatogenesis (PRM1, GATA4). Thymol co-administration with SiO₂-NPs significantly mitigated these adverse effects by restoring antioxidant levels, reducing inflammation, and improving gene expression and the histological architecture of the testes. The findings suggest that thymol has a promising protective role against SiO₂-NPs-induced male reproductive toxicity through its antioxidant and anti-inflammatory actions.

PMID:40615456 | PMC:PMC12227668 | DOI:10.1038/s41598-025-07769-x

A homozygous frameshift variant in the CILK1 gene causes cranioectodermal dysplasia - July 4, 2025

Eur J Hum Genet. 2025 Jul 4. doi: 10.1038/s41431-025-01902-0. Online ahead of print.

ABSTRACT

Cranioectodermal dysplasia (CED) is a ciliopathy characterized by skeletal and ectodermal abnormalities, renal failure, and liver fibrosis. Pathogenic variants in genes that encode the intraflagellar transport (IFT) complex components, particularly IFT-A, are responsible for approximately two-thirds of the CED cases. However, the cause of the remaining cases remains unknown. Ciliogenesis-associated kinase 1 (CILK1) is a highly conserved ciliary serine/threonine kinase with an N-terminal catalytic domain responsible for kinase activity and a C-terminal non-catalytic domain that interacts with the IFT-B complex. Biallelic variants in the catalytic domain are associated with lethal skeletal dysplasia, endocrine cerebroosteodysplasia, and short-rib polydactyly syndrome. No human disease has been linked to biallelic variants in the non-catalytic domain. We present a homozygous frameshift variant in the CILK1 gene that affects the distal part of the non-catalytic domain, causing CED in five patients from two pedigrees. All the patients survived into childhood and had disproportionately short stature, skeletal abnormalities, ectodermal dysplasia, renal issues, and liver complications. Functional data from patient-derived cells and the C. elegans model indicate that the variant reduces cilia number, increases cilia length, and disrupts the localization of IFT components. In contrast, the ciliary localization of CILK1 bearing the variant itself remains unaffected. Notably, we rescued the majority of these abnormalities by reintroducing CILK1 into patient-derived cells. Finally, our study describes CILK1 as a novel causal gene and the first non-IFT protein-encoding gene in the etiology of CED, thus expanding the known genotypic, mechanistic, and phenotypic spectrum of CED.

PMID:40615527 | DOI:10.1038/s41431-025-01902-0

Microplastics interaction with bisphenol A: Adsorption, desorption, and in vitro biological effects - July 3, 2025

Sci Total Environ. 2025 Jul 2;993:179971. doi: 10.1016/j.scitotenv.2025.179971. Online ahead of print.

ABSTRACT

Microplastic (MP) pollution is an increasing environmental concern due to its persistence and potential risks to both ecosystems and human health. Additionally, MPs can adsorb and become vehicle of other pollutants and hazardous chemicals. Among these, Bisphenol A (BPA) is a well-known endocrine disruptor. This study investigates the effects of MPs exposure in multiple cell types (preadipocytes, hepatocytes, hypothalamic neurons, and endothelial cells), the adsorption/desorption dynamics of BPA on MPs and the biological effects of BPA-sorbed MPs. We employed 5 μm commercial polystyrene microplastics (PS-MPs), both in their pristine form and with carboxyl (-COOH) functionalization, mimicking surface oxidation resulting from environmental weathering. While exposure to a wide range of pristine PS-MPs concentrations did not affect cell viability, COOH-functionalized PS-MPs induced significant toxicity in neurons and endothelial cells at high concentrations (>100 μg/mL). Furthermore, COOH-functionalized MPs altered lipid accumulation during preadipocyte to adipocyte differentiation. Using an optimized HPLC-MS/MS method with online SPE, we quantified the adsorption of BPA onto PS-MPs in water and its subsequent desorption under physiological conditions, achieving detection and quantification limits (3 ng/mL and 10 ng/mL, respectively) that enabled accurate BPA measurements, particularly in desorption studies. COOH-functionalized PS-MPs exhibited higher BPA adsorption efficiency and an increased desorption in cell culture media (29 % adsorption; 45 % desorption) compared to pristine PS-MPs (23 % adsorption; 13 % desorption), suggesting that oxidized MPs may act as more effective carriers for toxic chemicals. However, when cells were exposed to BPA-sorbed PS-MPs, no synergistic effects between the two pollutants were observed. These findings underscore the pivotal role of MP surface chemistry in governing pollutant interactions and shaping biological responses. Additionally, they emphasize the importance of assessing pollutant adsorption onto MPs; this approach, rather than using simple co-exposure methods, is essential for studying the role of MPs as carriers of environmental pollutants in biological systems.

PMID:40609415 | DOI:10.1016/j.scitotenv.2025.179971

Central-peripheral neuroimmune dynamics in psychological stress and depression: insights from current research - July 3, 2025

Mol Psychiatry. 2025 Jul 3. doi: 10.1038/s41380-025-03085-y. Online ahead of print.

ABSTRACT

Psychological stress plays a critical role in the onset of depression by activating neuroimmune and endocrine responses, leading to dysregulation of the hypothalamic-pituitary-adrenal axis and increased inflammation. This imbalance impacts key brain regions involved in mood regulation, such as the prefrontal cortex, hippocampus, and amygdala, contributing to the development of depressive symptoms. Moreover, stress induces immune dysregulation and inflammation in peripheral organs, including the gut, spleen, liver, lungs, and heart, which can result in metabolic disorders, cardiovascular disease, and immune dysfunction. Chronic stress also disrupts gut microbiota and alters the gut-brain axis via the vagus nerve, further exacerbating stress-related mental health issues. The cumulative effect of stress on peripheral organs significantly impacts both physical and mental health, linking systemic dysfunction to depression. This comprehensive review delves into the intricate mechanisms by which the immune system regulates mood and explores the etiological factors underlying dysregulated inflammatory responses in depression. We also summarize the connections between the brain and peripheral organs-bone marrow, spleen, gut, adipose tissue, heart, liver, lungs, and muscles-highlighting their coordinated regulation of immune function in response to psychological stress. Additionally, we investigate specific brain regions and neuronal populations that respond to stress stimuli, transmitting signals through autonomic and neuroendocrine pathways to modulate immune function. Finally, we discuss emerging therapeutic strategies that leverage the interaction between endocrine signaling and inflammatory responses for the effective treatment of depression.

PMID:40610703 | DOI:10.1038/s41380-025-03085-y

Per- and polyfluoroalkyl substances, genetic factors, and sleep health in reproductive-aged women: a cross-sectional study of the Shanghai Birth Cohort - July 3, 2025

Environ Int. 2025 Jun 30;202:109656. doi: 10.1016/j.envint.2025.109656. Online ahead of print.

ABSTRACT

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) may exert neurotoxic effects and disrupt endocrine function. However, the relationship between PFAS exposure and sleep disturbances in reproductive-aged women, and its interaction with genetic susceptibility, remains unclear. This study included 971 women from the Shanghai Birth Cohort preconception cohort. A total of 22 PFAS were measured in plasma, and sleep quality was assessed using the Pittsburgh Sleep Quality Index. Modified Poisson regression and quantile g-computation models estimated the effects of individual PFAS and PFAS mixtures on sleep disturbances. Polygenic risk scores were used to evaluate the cumulative genetic effects of sleep disturbances. 6:2Cl-PFESA was associated with increased snoring and less daytime dysfunction, though these associations did not remain significant after FDR correction. Exposure to PFAS mixtures was significantly associated with an increased risk of snoring (RR: 2.02, 95 % CI: 1.06-3.83). Significant associations between PFNA, PFDA, branched PFOS isomers, and chlorinated PFOS alternatives and increased snoring risk were observed in women with a high genetic predisposition. PFAS exposures and genetic variants showed additive effects on snoring risk, with RERI of 1.19 for PFNA, 1.06 for PFDA, 4.18 for 8: 2Cl - PFESA, 0.43 for 6: 2Cl - PFESA, 5.96 for 3 m-PFOS, 11.11 for 1 m - PFOS, and 0.40 for n-PFOS. These findings suggest PFAS exposure, particularly emerging alternatives and isomers of PFOS, may increase snoring risk in reproductive-aged women with a higher genetic predisposition.

PMID:40609510 | DOI:10.1016/j.envint.2025.109656

Toxicological Effects of Micro/Nano-plastics on Human Reproductive Health: A Review - July 3, 2025

Toxicol Lett. 2025 Jul 1:S0378-4274(25)00127-4. doi: 10.1016/j.toxlet.2025.06.021. Online ahead of print.

ABSTRACT

Micro/Nano-plastics (MNPs), including microplastics (MPs; <5mm) and nanoplastics (NPs; <100nm), have become pervasive environmental pollutants due to extensive plastic production and insufficient recycling practices. These particles originate from the degradation of larger plastic materials through processes such as photo-oxidation, thermo-oxidation, and incomplete biodegradation, resulting in chemically reactive fragments that persist in air, water, and food. Once released, MNPs enter the human body primarily via ingestion, inhalation, and dermal absorption, ultimately accumulating in various tissues, including reproductive organs. This review provides a comprehensive summary of current knowledge regarding the toxicological effects of MNPs on male and female reproductive health, with a focus on mammalian models and relevance to human exposure. In males, MNPs have been associated with testicular damage, impaired spermatogenesis, reduced sperm count and motility, and disruptions in the hypothalamic-pituitary-gonadal axis. In females, exposure has been linked to altered folliculogenesis, disrupted ovarian hormone levels, impaired oocyte quality, and placental dysfunction. These effects are largely driven by mechanisms involving oxidative stress, inflammation, endocrine disruption, mitochondrial dysfunction, and apoptosis. Furthermore, MNPs have been shown to disrupt gut microbiota composition, contributing to systemic inflammation and reproductive dysfunction through emerging pathways such as the gut-testis axis. Given their widespread presence and multifaceted modes of action, MNPs pose a serious threat to human reproductive health. Therefore, there is an urgent need for stricter environmental regulations, improved waste management, and further research to understand the long-term and transgenerational consequences of MNP exposure.

PMID:40609962 | DOI:10.1016/j.toxlet.2025.06.021

Formation of PCB-like and PCDF-like transformation products from liquid crystal monomers in aqueous chlorination: Degradation, transformation and toxicity evaluation - July 3, 2025

J Hazard Mater. 2025 Jun 27;495:139091. doi: 10.1016/j.jhazmat.2025.139091. Online ahead of print.

ABSTRACT

Liquid crystal monomers (LCMs) are persistent, bioaccumulative and toxic emerging contaminants that are widely detected in various environmental compartments including wastewater. However, scarce information is available regarding the fate of LCMs upon wastewater treatment. The current work is the first study to investigate the degradation, transformation fate and toxicity of LCMs upon chlorination, using 4'-propoxy-4-biphenylcarbonitrile (3OCB) and 1-ethoxy-2,3-difluoro-4-(4-propylphenyl)benzene (2OdF3B) as model LCMs. A total of 34 transformation products (TPs) were identified and structurally elucidated, some of which possessed similar chemical structures to the legacy persistent organic pollutants (POPs) - "polychlorinated biphenyls" (PCBs) and "polychlorinated dibenzofurans" (PCDFs). With in silico toxicity assessment, most of the generated TPs showed potential developmental toxicity, mutagenicity, endocrine disruption and protein binding ability compared to the parent compounds. Further toxicity assessments, as well as epidemiology studies, to reveal the hazards of these PCB-like and PCDF-like TPs are urgently needed.

PMID:40609473 | DOI:10.1016/j.jhazmat.2025.139091

Microplastics interaction with bisphenol A: Adsorption, desorption, and in vitro biological effects - July 3, 2025

Sci Total Environ. 2025 Jul 2;993:179971. doi: 10.1016/j.scitotenv.2025.179971. Online ahead of print.

ABSTRACT

PMID:40609415 | DOI:10.1016/j.scitotenv.2025.179971

Per- and polyfluoroalkyl substances, genetic factors, and sleep health in reproductive-aged women: a cross-sectional study of the Shanghai Birth Cohort - July 3, 2025

Environ Int. 2025 Jun 30;202:109656. doi: 10.1016/j.envint.2025.109656. Online ahead of print.

ABSTRACT

PMID:40609510 | DOI:10.1016/j.envint.2025.109656

Maternal exposure to pesticides and gestational diabetes mellitus in the Elfe cohort - July 3, 2025

Environ Res. 2025 Jul 1;284:122275. doi: 10.1016/j.envres.2025.122275. Online ahead of print.

ABSTRACT

BACKGROUND: Gestational diabetes mellitus (GDM) increases risks of adverse perinatal outcomes and metabolic disorders in offspring. Some endocrine-disrupting chemicals are presumed to interfere with glucose metabolism. We aimed to assess the association between non-occupational exposures to pesticides and the risk of GDM.

METHODS: The study was conducted on 11 512 women (791 with GDM) from the French nationwide Elfe cohort. Among 114 suspected pesticides identified using a toxicogenomic approach, 62 with detection frequency ≥10 % were analyzed across three sources of exposure: residential use (self-reported, n = 18), agricultural (geographic information system, n = 14) and dietary (estimated by a food-frequency questionnaire and monitoring data of pesticide residues in foods, n = 30). The association between exposure to pesticides (no or low vs. high) and the occurrence of GDM was tested with single and multi-source adjusted logistic regression models.

RESULTS: In the multi-source model, dietary exposure to glyphosate (aOR = 0.6, 95 %CI: 0.5,0.9) or agricultural exposure (aOR = 0.8, 95 %CI:0.6,1.0) were associated with lower odds of GDM. The same effect was identified for two dietary pesticides: epoxiconazole (aOR = 0.6, 95 %CI: 0.5,0.8) and penconazole (aOR = 0.8, 95 %CI: 0.6,1.0). Dietary exposure to cypermethrin (aOR = 1.2, 95 %CI:1.0,1.5) and agricultural exposure to myclobutanil (aOR = 1.4, 95 %CI:1.1,1.9) were associated with higher odds of GDM. No significant association was identified for the residential use of pesticides.

CONCLUSION: This toxico-genomic-based study identifies five pesticides associated with GDM through agricultural or dietary exposure. These findings provide new insights into environmental contributors to GDM. Further research is needed to elucidate the underlying toxicological mechanisms and confirm these associations.

PMID:40609722 | DOI:10.1016/j.envres.2025.122275

In Vivo Screening Evaluation of 12 Chemicals as Candidate Endocrine Disruptors Using Ovariectomized Mouse Uterotrophic Bioassay - July 3, 2025

Regul Toxicol Pharmacol. 2025 Jul 1:105900. doi: 10.1016/j.yrtph.2025.105900. Online ahead of print.

ABSTRACT

The rodent uterotrophic bioassay is helpful to easily predict and evaluate the estrogenic properties of chemicals by measuring changes in uterine weight as a screening test. We used this assay in ovariectomized (OVX) mice to screen 12 chemicals suspected to be estrogenic or antiestrogenic properties by in vitro assays in the screening project of the Ministry of Health, Labour and Welfare, Japan. We administered each chemical to 8-week-old OVX mice either orally (po) or by subcutaneous (sc) injection at 24-hr intervals for 7 consecutive days. Ethinyl estradiol was used as reference control. Our study revealed for the first time that po or sc administration of 1,1,1-tris(4-hydroxyphenyl)ethane exerted estrogenic effects at nontoxic dose, with a LOEL of 300 mg/kg for both routes. In contrast, sc administration, but not po administration, of dibenzoylmethane, tricresyl phosphate, and triphenylsilanol exerted antiestrogenic effects, with a LOEL of 30 mg/kg for each chemical. Furthermore, po and sc administration of 4,4'-butylidenebis[6-tert-butyl-3-methylphenol] exerted antiestrogenic effects, with a LOEL of 100 mg/kg for both routes. Taken together, we revealed that only 5 of the 12 substances of concern in vitro were active in vivo, which could be helpful for the effective detection of estrogenic and antiestrogenic activities. The five positive substances were considered to require further consideration in the prioritization list of higher-order toxicity testing for their endocrine disrupting effects.

PMID:40609822 | DOI:10.1016/j.yrtph.2025.105900

Toxicological Effects of Micro/Nano-plastics on Human Reproductive Health: A Review - July 3, 2025

Toxicol Lett. 2025 Jul 1:S0378-4274(25)00127-4. doi: 10.1016/j.toxlet.2025.06.021. Online ahead of print.

ABSTRACT

PMID:40609962 | DOI:10.1016/j.toxlet.2025.06.021

Advances in lenvatinib monotherapy and combination therapies in anaplastic thyroid cancer (Review) - July 3, 2025

Oncol Lett. 2025 Jun 11;30(2):393. doi: 10.3892/ol.2025.15139. eCollection 2025 Aug.

ABSTRACT

Anaplastic thyroid cancer (ATC) is a highly malignant and aggressive endocrine tumor with the poorest prognosis among all thyroid cancer (TC) subtypes. Although ATC is extremely rare, treatment remains a notable challenge, as traditional therapies have exhibited very limited efficacy. Targeted small-molecule inhibitors that disrupt molecular signaling pathways offer a potential therapeutic approach for patients with ATC. Lenvatinib, a tyrosine kinase inhibitor, has emerged as a promising therapeutic agent, which targets various factors involved in angiogenesis and tumor progression, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor α, fibroblast growth factor receptor and mast/stem cell growth factor receptor. Preclinical and clinical trials have demonstrated the efficacy of lenvatinib, both as monotherapy and in combination with other targeted therapy, chemotherapy, immunotherapy, warranting a comprehensive review of these studies. However, lenvatinib monotherapy was associated with a high incidence of adverse events (including hypertension, anorexia and proteinuria) and certain limitations, particularly drug resistance, emphasizing the need for optimized therapeutic strategies. In the present review, the efficacy and safety of lenvatinib monotherapy and combination therapies in the treatment of ATC were examined. Furthermore, the feasibility and limitations of different combination therapies were analyzed and compared. The present review aimed to provide insights into potential lenvatinib-based regimens that could enhance survival outcomes and improve the quality of life for patients with ATC in the future.

PMID:40606309 | PMC:PMC12214766 | DOI:10.3892/ol.2025.15139

Treatment-resistant sleep apnea due to untreated hypothyroidism - July 3, 2025

Acta Clin Belg. 2025 Jul 3:1-8. doi: 10.1080/17843286.2025.2528023. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep apnea is a common disorder characterized by recurrent episodes of upper airway obstruction or impaired respiratory drive, leading to disrupted sleep and significant cardiopulmonary consequences. While anatomical and neuromuscular factors are well-established contributors to obstructive sleep apnea (OSA), and central sleep apnea (CSA) is often linked to cardiac or neurological conditions, the impact of endocrine disorders, particularly hypothyroidism, is frequently overlooked.

CLINICAL PRESENTATION: We describe a case of severe sleep apnea that exhibited persistent sleep apnea (including obstructive, but also central and mixed events) under continuous positive airway pressure (CPAP) therapy. Clinical and biochemical findings confirmed profound hypothyroidism with myxedema. Thyroid hormone replacement therapy led to substantial clinical improvement, including weight loss, normalization of thyroid function, and a marked reduction in residual AHI after eight months.

CONCLUSION: This case highlights the need for increased awareness of hypothyroidism as a potential and reversible cause of treatment-resistant sleep apnea (TRSA). Thyroid hormone replacement therapy can lead to significant improvement, emphasizing the need for routine thyroid function screening in patients with sleep apnea.

PMID:40607709 | DOI:10.1080/17843286.2025.2528023

Excess and reduced work absence during COVID-19 in Poland: insights from cause-specific time-series models - July 3, 2025

Popul Health Metr. 2025 Jul 2;23(1):35. doi: 10.1186/s12963-025-00400-1.

ABSTRACT

BACKGROUND: The COVID-19 pandemic profoundly disrupted workplace attendance, yet its impact on cause-specific work absence remains largely unexplored.

AIM: To estimate the cause-specific excess/reduced work absence associated with COVID-19 in Poland.

METHODS: Following the concept of excess mortality, we define excess work absence as the difference between observed and expected absence, where the latter reflects the level anticipated in the absence of the pandemic. Using time-series analysis (Seasonal Autoregressive Integrated Moving Average) on pre-pandemic (2012-2019) quarterly (Q) social insurance data, we forecasted absence rates for disease groups (classified by ICD-10 chapters) and caregiving-related absenteeism. Forecasted absence rates were then compared to observed values during 2020-2024, allowing for the identification of excess or reduced work absence.

RESULTS: We observed notable deviations in work absence rates during the pandemic period (until the end of Q1-2022). The highest excess absence was identified in caregiving-related absenteeism at the pandemic's onset, exceeding expected levels by over fivefold. A mental health crisis that began with the pandemic resulted in four consecutive quarters of excess absence, reaching a 54% excess in Q2-2020. We identified a notable excess absence in three ICD-10 chapters that reflect the indirect effects of the pandemic, such as increased diagnostic uncertainty, modified coding practices during early COVID-19 waves, and widespread implementation of public health interventions. Absence rates were lower than expected in neoplasms, endocrine and digestive diseases until the end of the pandemic period, likely reflecting reduced healthcare accessibility. Similarly, absence related to injuries and poisoning was below the expected level until mid-2022, indicating decreased social mobility.

CONCLUSIONS: COVID-19 substantially reshaped work absence patterns in Poland, particularly during the early pandemic phase. Pronounced increases and decreases were identified across disease categories. These diverging trends plausibly reflect both the COVID-19's effects on the development of other conditions and disruptions in healthcare access. These findings highlight the need for disease-specific policy responses to mitigate future health crises and ensure continuity of care during pandemics.

PMID:40604897 | PMC:PMC12219963 | DOI:10.1186/s12963-025-00400-1

Impact of prenatal Di(2-ethylhexyl) phthalate exposure on pubertal development in female offspring rats: A focus on ERα-Mediated IGF-1/NKB crosstalk in the hypothalamus - July 2, 2025

Sci Rep. 2025 Jul 1;15(1):22255. doi: 10.1038/s41598-025-08253-2.

ABSTRACT

Di(2-ethylhexyl) phthalate (DEHP), renowned for its efficacy in enhancing the pliability of plastic products, serves predominantly as a plasticizer and additive in the plastics industry. A growing body of research in both animal models and human populations has elucidated that the maternal environment prior to birth exerts a significant influence on the growth and development of offspring. Consequently, our research is designed to investigate the effects of prenatal DEHP exposure on the pubertal reproductive development of female rat offspring and to decipher the underlying mechanisms. This study utilized Wistar rats as the experimental animal model, with exposure to varying doses of DEHP during pregnancy for group allocation and treatment. Transmission electron microscopy was used to examine ultrastructural changes in the hypothalamus of DEHP-exposed female offspring rats. High-performance liquid chromatography (HPLC) was employed to quantitatively analyze the amino acid levels in the hypothalamus of the female offspring. Enzyme-linked immunosorbent assay (ELISA) was used to quantitatively measure hormone levels in both the hypothalamus and peripheral blood. Immunohistochemistry was applied to quantify the expression of ERα and GnRH in the hypothalamus. Additionally, precise immunofluorescence analysis was conducted to assess the expression levels of IGF-1 and NKB in the rat hypothalamus. Spearman correlation analysis was employed to elucidate the associations between key factors in the hypothalamus. Our findings reveal that prenatal exposure to Di(2-ethylhexyl) phthalate (DEHP) precipitates the onset of puberty in female rat offspring, concurrently altering the expression of key puberty-regulating genes in the hypothalamus. This elucidation sheds light on the molecular mechanisms underpinning the role of hypothalamic ERα in modulating the IGF-1 and NKB pathways, contributing to DEHP-induced precocious puberty in females, and underscores the critical regulatory function of IGF-1/NKB crosstalk in this phenomenon. Consequently, our research posits that prenatal exposure to DEHP is likely transmitted from the mother to the embryo, precipitating developmental anomalies and the onset of precocious puberty in offspring. This underscores the significance of pregnancy as a pivotal period for endocrine disruption, offering a novel theoretical foundation for the prophylaxis and management of precocious puberty in female children.

PMID:40595203 | PMC:PMC12218987 | DOI:10.1038/s41598-025-08253-2

Degradation of bisphenol a using zinc oxide decorated by nickel ferrite nanoparticles toward persulfate activation in the presence of ultraviolet radiation - July 2, 2025

Sci Rep. 2025 Jul 1;15(1):20758. doi: 10.1038/s41598-025-93968-5.

ABSTRACT

Bisphenol-A (BPA), a commonly used chemical in the production of thermal paper and kinetic polymers, acts as an endocrine disruptor, leading to biological accumulation in the environment and posing long-term risks to human health. This study aimed to assess the degradation of BPA using persulfate (PS) activated by nickel ferrite-anchored zinc oxide (ZnO@NiFe₂O₄) nanoparticles in the presence of ultraviolet (UV) radiation. The ZnO@NiFe₂O₄ catalyst was synthesized using a co-precipitation method. Its structure was characterized through FESEM, EDS, XRD, VSM, DRS, TEM, and PL analyses. Several parameters including solution pH, initial BPA concentration, and catalyst and PS dosages were examined. Additionally, the influence of interfering ions such as nitrate, chloride, sulfate, carbonate, and bicarbonate was evaluated. Total organic carbon (TOC) analysis was conducted to measure BPA mineralization throughout the process. Lastly, the reusability of the photocatalyst and the overall efficiency of the process were assessed. Under optimal conditions (pH = 9, BPA concentration = 0.04 g/L, catalyst dosage = 0.3 g/L, and PS = mM), the highest removal efficiency and mineralization of BPA after 15 min were found to be > 99.9% and 59.21%, respectively. However, interfering ions reduced the BPA degradation efficiency in order of Cl^- (51.75%) < SO₄^-2 (70.61%) < NO₃^- (75.41%) < CO₃^-2 (82.41%). After four recovery cycles, the catalyst's effectiveness decreased to 15.7%. The photocatalytic oxidation of BPA adhered to pseudo-first-order kinetics (k = 0.23 min^-1). In conclusion, the PS activated by ZnO@NiFe₂O₄/UV proved to be effective for BPA degradation due to its strong performance and high recovery capability.

PMID:40596690 | PMC:PMC12216373 | DOI:10.1038/s41598-025-93968-5

Maternal exposure to specific endocrine-disrupting chemicals and gestational diabetes mellitus: systematic review and meta-analysis - July 2, 2025

Sci Rep. 2025 Jul 2;15(1):23487. doi: 10.1038/s41598-025-05049-2.

ABSTRACT

This meta-analysis examines the relationship between exposure to endocrine-disrupting chemicals, such as phthalates and parabens, which are commonly found in cosmetics, and the risk of developing gestational diabetes mellitus (GDM). Following a systematic search of databases (including PubMed, Scopus, and Web of Science), 14 relevant studies involving 9,503 pregnant women from various regions were identified. After excluding one paper, 11 studies were classified as high-quality, while three received acceptable scores and were included in the analysis. The studies assessed the level of chemical exposure by analyzing urine, serum, or plasma samples. Calculated odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the potential association between maternal exposure and GDM development. The pooled analysis indicated no significant correlation between phthalate exposure during pregnancy and GDM risk, with an OR of 1.01 (95% CI: 0.95-1.08). Subgroup analyses based on participants' location and specific phthalate metabolites consistently showed no significant association with GDM. Limited evidence on parabens also failed to demonstrate a clear link with GDM. Although this meta-analysis found no significant link between these substances and GDM, further investigation is necessary to comprehensively assess the cumulative and long-term effects of endocrine-disrupting chemicals on pregnant women.

PMID:40603383 | PMC:PMC12223249 | DOI:10.1038/s41598-025-05049-2

Ophiocordyceps sinensis-induced changes in Thitarodes xiaojinensis: from intestinal barrier destruction, microbiome dysbiosis to immune responses at the molecular level - July 2, 2025

BMC Biol. 2025 Jul 1;23(1):183. doi: 10.1186/s12915-025-02277-w.

ABSTRACT

BACKGROUND: The entomopathogenic fungus (EPF) Ophiocordyceps sinensis has a long-term coexistence with its host insect, Thitarodes xiaojinensis, making it a unique model for host-pathogen interactions. Hemolymph, a critical component in insects, plays an essential role in maintaining both nutritional and immune homeostasis. However, the mechanism of the host's immune response remains unclear when O. sinensis proliferates in the hemolymph.

RESULTS: O. sinensis caused damage to the insect's intestinal barrier, facilitating the translocation of gut bacteria into the hemocoel. Subsequently, the presence of O. sinensis and opportunistic pathogenic bacteria from the gut disrupted the homeostasis of the hemolymph microbiota, resulting in an increase in bacterial diversity. This disruption triggered a series of physiological responses in the host, including elevated levels of endocrine hormones specifically 20-hydroxyecdysone (20E) and juvenile hormone 3 (JH3). Additionally, there was an enhancement of antioxidant capacity, as indicated by increased total antioxidant capacity and glutathione S-transferase activity, along with the production of antimicrobial peptides (AMPs) as part of the immune defense. Notably, the rise in 20E levels during O. sinensis infection might have significantly contributed to the increased production of AMPs.

CONCLUSIONS: O. sinensis infection significantly alters T. xiaojinensis physiology. Humoral immunity in infected hosts is primarily in response to hemolymph microbial homeostasis due to intestinal translocation. Among them, 20E upregulates AMP-related genes, suggesting a key immune strategy for managing microbial imbalances while tolerating fungal pathogens.

PMID:40597298 | PMC:PMC12220380 | DOI:10.1186/s12915-025-02277-w

Sex differences in endocrine, metabolic and psychological disturbance in obese patients with OSA - July 2, 2025

Biol Sex Differ. 2025 Jul 1;16(1):48. doi: 10.1186/s13293-025-00730-7.

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risks of glucolipid metabolic disruption, endocrine disturbances and psychological distress. There is scarce research regarding the influence of sex on these associations. The current study aimed to evaluate the effects of sex on metabolic, endocrine and psychological changes in patients with OSA.

METHODS: One hundred sixty-four young adult women and one hundred sixty-two age-matched men with OSA completed polysomnography assessments, questionnaires (including the Epworth Sleepiness Scale [ESS], Self-Reported Anxiety Scale [SAS], Self-Rating Depression Scale [SDS], and 12-Item Short-Form Health Survey [SF-12]) and biochemical analyses for glucolipid metabolism and endocrine function, including the pituitary-adrenal (PA), pituitary thyroid (PT), and pituitary-gonadal (PG) axes.

RESULTS: Homeostasis model assessment of insulin resistance (HOMA-IR), thyroid hormone and midnight PA axis activity levels were greater in female patients with severe OSA compared to those with mild-to-moderate OSA, and these metabolic and endocrine changes were associated with nocturnal hypoxia only in female patients. Additionally, midnight cortisol was associated with HOMA-IR (independent of anthropometry and sleep disturbance parameters) in females (β = 0.545, P = 0.012, adjusted R² = 0.217). ESS was higher for male patients with severe OSA compared to females with the same level of OSA (P = 0.003), and ESS was associated with nocturnal hypoxia in males (β = - 0.494, P = 0.001, adjusted R² = 0.224). SAS was higher for female patients with severe OSA compared to males with the same level of disease (P = 0.001).

CONCLUSIONS: The metabolic, endocrine and psychological consequences of OSA may differ across sexes. The associations of nocturnal hypoxia with glucose metabolic disturbance and the activation of the PA and PT axes were observed in females, whereas the association of nocturnal hypoxia with ESS was limited to males. This could indicate a distinct metabolic, endocrine and psychological phenotype for female patients with OSA, who may require different disease management strategies compared to males.

PMID:40598676 | PMC:PMC12219881 | DOI:10.1186/s13293-025-00730-7

Methimazole-induced reproductive endocrine system disruption and hepatotoxicity: insights from a Trichogaster trichopterus animal model - July 2, 2025

BMC Pharmacol Toxicol. 2025 Jul 1;26(1):128. doi: 10.1186/s40360-025-00942-y.

ABSTRACT

BACKGROUND: Methimazole is commonly prescribed for managing hyperthyroidism, although concerns regarding its reproductive and hepatic adverse effects persist. This study aimed to evaluate the dose-dependent effects of methimazole on reproductive endocrine system function and hepatic integrity using an animal model.

METHODS: Adult female three-spot gourami (Trichogaster trichopterus) were administered intramuscular injections of methimazole at doses of 0.025, 0.05, and 0.1 mg/kg body weight every other day for 20 days. Gonadosomatic Index (GSI), Hepatosomatic Index (HSI), sex steroid hormones (17β-estradiol, testosterone, 17-hydroxyprogesterone), liver enzymes (GOT, GPT), and histological alterations in ovarian and hepatic histology were assessed.

RESULTS: Methimazole significantly reduced GSI in a dose-dependent manner, with the lowest value (3.33%, P < 0.05) observed at the highest dose. Although HSI increased slightly, differences among groups were not significant. Dose-dependent declines were observed in sex steroid hormones, with the most pronounced reduction at 0.1 mg/kg (P < 0.05), indicating significant disruption in steroidogenesis and ovarian function. Liver enzymes activity GOT and GPT were significantly elevated at doses of 0.05 and 0.1 mg/kg (P < 0.05), reflecting hepatic stress and potential hepatotoxicity. Histological analyses demonstrated significant disruption in ovarian follicle maturation, with oocytes arrested at early growth stages at higher methimazole doses. Furthermore, structural liver damage including hepatocyte hypertrophy, inflammation, and necrosis was observed at the highest methimazole dose.

CONCLUSION: Methimazole induces notable reproductive and hepatic disturbances, highlighting the importance of monitoring endocrine and hepatic parameters during clinical methimazole therapy, especially in reproductive-age populations. These findings underscore the potential risks associated with methimazole treatment and suggest careful clinical monitoring to mitigate possible reproductive and hepatic adverse effects.

PMID:40598691 | PMC:PMC12217290 | DOI:10.1186/s40360-025-00942-y

Isothiazole Disinfectants Inhibit Neurosteroid Production by Targeting Human and Rat 5α-Reductase Type 1 - July 2, 2025

Chem Res Toxicol. 2025 Jul 2. doi: 10.1021/acs.chemrestox.5c00063. Online ahead of print.

ABSTRACT

Isothiazole disinfectants are widely used antimicrobial preservatives found in various consumer products, raising concerns about their potential effects on human health. This study investigated the inhibitory effects of seven isothiazole disinfectants on human and rat steroid 5α-reductase type 1 (SRD5A1), a key enzyme in neurosteroid biosynthesis. Among the tested compounds, dichlorooctylisothiazole exhibited the strongest suppression on human SRD5A1 with an IC₅₀ value of 3.23 μM, followed by octylisothiazole (5.10 μM), butylbenzo[d]isothiazol-3(2H)-one (16.51 μM), benzisothiazole (31.64 μM), and methylchloroisothiazole (42.65 μM). Enzyme kinetics and molecular docking analyses revealed that these compounds acted through mixed/noncompetitive inhibition by binding to the NADPH-binding pocket via van der Waals and hydrogen bonds. Cell-based studies in human SF126 glioblastoma cells confirmed that these compounds penetrated cell membranes and reduced dihydrotestosterone production. Structure-activity relationship analysis showed that compounds with higher LogP, molecular weight, volume, heavy atom number, and apolar desolvation exhibited stronger inhibitory activity. 3D quantitative structure-activity relationship analysis incorporated hydrogen bond acceptor and hydrophobicity domain features. Additionally, dichlorooctylisothiazole showed significant inhibition of rat SRD5A1 with an IC₅₀ of 21.47 μM. In conclusion, these findings reveal some isothiazole disinfectants as potential endocrine disruptors targeting neurosteroid biosynthesis via SRD5A1 and highlight clear structure-activity relationship and species-dependent variance.

PMID:40601901 | DOI:10.1021/acs.chemrestox.5c00063

Effects of polystyrene nanoplastics on the female reproductive system in mice: Implications for ovarian function and follicular development - July 2, 2025

Reprod Toxicol. 2025 Jun 30;136:108983. doi: 10.1016/j.reprotox.2025.108983. Online ahead of print.

ABSTRACT

INTRODUCTION: Plastic pollution has led to widespread accumulation of microplastics (MPs) and nanoplastics (NPs), increasing human exposure via ingestion, inhalation, and dermal contact. While MPs have been linked to endocrine and reproductive toxicity, studies on NPs, especially their effects on female reproductive health, remain limited. Given their smaller size and greater bioavailability, NPs may cross biological barriers and accumulate in reproductive tissues. This study examines the effects of oral polystyrene nanoplastics (PS-NPs) on estrous cyclicity, follicle development, atresia, corpora lutea formation, and serum hormone levels in female mice.

MATERIALS AND METHODS: Female C57BL/6 mice were orally exposed to water (control) or PS-NPs (100 µg/L or 1000 µg/L) daily for 29 days. Vaginal lavage samples were collected during the last 15 days to monitor estrous cyclicity. At study completion, mice were euthanized, and blood and ovarian tissues were collected for analysis. Ovaries were processed for histological evaluation, and serum hormone levels were quantified using ELISA.

RESULTS: PS-NPs exposure significantly increased estrous cycle length in the high-dose group compared to control (5.53 ± .80 days vs 4.70 ± 0.71 days, P = 0.02). Serum progesterone levels were significantly reduced in the high-dose group compared to control (mean difference = 1.64 pg/mL, standard error of difference (SED) = 0.64, P = 0.03). Antral follicle diameter decreased significantly in both exposure groups compared to control, with a more pronounced reduction at the higher dose (P = 0.001). Additionally, chronic PS-NPs exposure led to a significant decrease in corpora lutea density and a significant increase in atretic follicle density in the high exposure group compared to control (mean difference = 1.46, SED = 0.52, P = 0.02 & mean difference = 3.01, SED = 0.95, P = 0.01 respectively).

CONCLUSION: Chronic PS-NPs exposure in female mice disrupted ovarian function as evidenced by a dose-dependent reduction in antral follicle size, decreased corpora lutea density, increased atretic follicle density, prolonged estrous cycles, and decreased serum progesterone levels, suggesting potential implications for anovulation, infertility, and other reproductive disorders. Future studies should further investigate the mechanisms underlying NPs-induced reproductive toxicity.

PMID:40602670 | DOI:10.1016/j.reprotox.2025.108983

Adrenal insufficiency unmasked following laparoscopic sleeve gastrectomy: A rare case report - July 2, 2025

Int J Surg Case Rep. 2025 Jun 30;133:111595. doi: 10.1016/j.ijscr.2025.111595. Online ahead of print.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Laparoscopic sleeve gastrectomy (LSG) is a common bariatric surgery with proven metabolic benefits. However, it can trigger endocrine disturbances, including adrenal insufficiency (AI). AI is rare but potentially life-threatening, and its symptoms often mimic normal postoperative recovery, leading to delayed diagnosis. This overlap may obscure early recognition in post-LSG patients.

CASE PRESENTATION: A report a 49-year-old woman who developed fatigue, anorexia, orthostatic hypotension, and hyponatremia four weeks post-LSG. Initial symptoms were attributed to expected recovery. Persisting signs prompted hormonal testing, which revealed low cortisol and an inadequate response to cosyntropin stimulation, confirming secondary AI. Hydrocortisone therapy was initiated, resulting in rapid symptom resolution and biochemical normalization.

CLINICAL DISCUSSION: Postoperative physiological stress and rapid weight loss may disrupt hypothalamic-pituitary-adrenal function. Secondary AI lacks hallmark signs, making diagnosis particularly challenging after LSG. This case emphasizes the need to consider AI in patients with disproportionate fatigue and electrolyte imbalance. Timely diagnosis and treatment are crucial to prevent adrenal crisis.

CONCLUSION: AI is a rare but serious postoperative complication of LSG. Its recognition is hindered by nonspecific symptoms and diagnostic overlap with normal recovery. Endocrine evaluation should be considered in atypical or prolonged postoperative courses. Early intervention improves outcomes and may prevent life-threatening complications.

PMID:40602169 | DOI:10.1016/j.ijscr.2025.111595

Suppression of human and rat 17β-hydroxysteroid dehydrogenase 1 by salicylate preservatives: 3D quantitative structure-activity relationship and in silico docking analysis - July 2, 2025

J Steroid Biochem Mol Biol. 2025 Jun 30;254:106823. doi: 10.1016/j.jsbmb.2025.106823. Online ahead of print.

ABSTRACT

The placenta contains 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1), an enzyme critical for converting estrone to estradiol. Salicylates, widely used as preservatives, may inhibit 17β-HSD1, but their inhibitory strength and structure-activity relationships (SAR) remain unclear. This study evaluated 13 structurally diverse salicylates, identifying potent inhibitors of human and rat 17β-HSD1. Menthyl salicylate showed the strongest inhibition in humans (IC₅₀: 5.23 μM) and rats (IC₅₀: 14.85 μM). Inhibition correlated negatively with molecular weight, volume, carbon chain length, and LogP. Mechanistic studies revealed mixed/noncompetitive inhibition in both species. 3D-QSAR and molecular docking highlighted hydrophobic, van der Waals, and hydrogen-bonding interactions at the enzyme's active site. Key structural features, including carbon chain length and substituent patterns, determined inhibitory potency. These findings clarify SAR and suggest salicylates' potential as endocrine disruptors.

PMID:40602440 | DOI:10.1016/j.jsbmb.2025.106823

Chronic exposure to low concentration of metamifop induces reproductive endocrine disruption and courtship behavior disorders in zebrafish (Danio rerio) - July 2, 2025

Environ Res. 2025 Jun 30;284:122261. doi: 10.1016/j.envres.2025.122261. Online ahead of print.

ABSTRACT

Metamifop, an aryloxyphenoxypropionate herbicide, is considered a threat to non-target organisms due to its widespread use and potential toxicity. However, there remains a significant gap in data regarding reproductive endpoints following exposure to metamifop at environmentally relevant concentrations. In this study, metamifop showed a moderate ability to bioconcentrate in zebrafish. Exposure to metamifop at environmental concentrations resulted in reduced egg production, suppression of courtship behavior, adverse effects on gonadal development and offspring development. The balance of testosterone, estradiol and vitellogenin levels was disturbed in the group treated with sublethal concentrations of metamifop. RNA-seq analysis of zebrafish gonads revealed abnormalities in the transcription of the steroid hormone biosynthesis pathway. Further results showed that genes important in the hypothalamus-pituitary-gonadal-liver (HPGL) axis involved in steroid hormone biosynthesis (era, gnrh3, fshr, hsd3b, cyp19a, hsd17b and vtg1) were significantly altered. In addition, we found potential binding effects between metamifop and the homology modeling proteins of aromatase CYP19A and estrogen receptor ERα. Overall, our study demonstrated the reproductive endocrine-disrupting effects of metamifop on zebrafish and preliminarily elucidated its mechanism, providing new insights into the environmental risk assessment of metamifop on aquatic organisms.

PMID:40602518 | DOI:10.1016/j.envres.2025.122261

Effects of polystyrene nanoplastics on the female reproductive system in mice: Implications for ovarian function and follicular development - July 2, 2025

Reprod Toxicol. 2025 Jun 30;136:108983. doi: 10.1016/j.reprotox.2025.108983. Online ahead of print.

ABSTRACT

PMID:40602670 | DOI:10.1016/j.reprotox.2025.108983

Revolutionizing toxicity predictions of diverse chemicals to protect human health: Comparative QSAR and q-RASAR modeling - July 2, 2025

Toxicol Lett. 2025 Jul 1;411:16-24. doi: 10.1016/j.toxlet.2025.06.019. Online ahead of print.

ABSTRACT

The extensive application of chemicals in the form of pesticides, cosmetics, drugs, etc., has been shown to adversely affect humans and the environment, mainly through food product residues and environmental exposure. Exposure to diverse chemicals through various routes including ingestion, inhalation, and dermal contact is associated with multiple health risks including endocrine disruption, cancer, and neurotoxicity. This study presents an advanced computational approach using quantitative structure-activity relationship (QSAR) and quantitative read-across structure-activity relationship (q-RASAR) models to predict the acute toxicity of diverse chemicals in humans, with the negative logarithm of the lowest published toxic dose (pTDLo) endpoint. We developed the first-ever predictive toxicity models combining QSAR and similarity-based read-across techniques to enhance accuracy, utilizing the TOXRIC database. The q-RASAR model outperformed traditional QSAR approaches, achieving robust statistical performance with internal validation metrics of R² = 0.710, Q² = 0.658, and external validation metrics of Q²_F1 = 0.812, Q²_F2 = 0.812, Δr²_m(test) = 0.087 and r_m(test)²̅ = 0.741. The model identified the key structural features, such as high coefficients and variations in similarity values among closely related compounds, the presence of carbon-carbon bonds at specific topological distances (5 and 8), and higher minimum E-state indices, all of which are linked to increased toxicity toward humans. The PLS-based q-RASAR model was further utilized to screen pesticides obtained from the pesticide properties database (PPDB) and 3660 investigational drugs from the DrugBank database for potential toxicants in humans, providing a tool to identify hazardous substances and mitigate risks. The developed models are instrumental in filling eco-toxicological data gaps and facilitating the development of novel, safe, and eco-friendly chemicals.

PMID:40602695 | DOI:10.1016/j.toxlet.2025.06.019

SREBP-1 in obesity-induced breast cancer: mechanisms and therapeutic perspectives - July 2, 2025

Mol Biol Rep. 2025 Jul 1;52(1):663. doi: 10.1007/s11033-025-10775-x.

ABSTRACT

Breast cancer is the most prevalent form of malignant cancer among women worldwide, and obesity is a significant risk factor. Sterol regulatory element-binding protein 1 (SREBP-1) is a crucial transcription factor that governs lipid synthesis and is aberrantly activated in obesity-induced breast cancer. This review examines the intricate relationship between SREBP-1, obesity, and breast cancer, emphasizing the mechanisms by which obesity-induced activation of SREBP-1 facilitates tumor growth, metastasis, and therapeutic resistance. Obesity disrupts the PI3K/AKT/mTOR and AMPK pathways, resulting in hyperactivation of SREBP-1 and excessive lipid accumulation in breast cancer cells. This metabolic reprogramming fosters a tumor-supportive microenvironment, thereby enhancing cancer cell proliferation, survival, and epithelial-mesenchymal transition. Moreover, obesity adversely affects various breast cancer therapies, including surgery, radiotherapy, chemotherapy, endocrine therapy, and immunotherapy by inducing drug resistance and exacerbating side effects. Targeting SREBP-1 and its regulatory pathways is a promising therapeutic strategy for obesity-induced breast cancer. Natural compounds and small molecules such as fatostatin, mollugin, xanthohumol, and docosahexaenoic acid have demonstrated potential in inhibiting SREBP-1 activation and reducing lipid synthesis in breast cancer cells. Integrating these targeted therapies with conventional treatments may enhance the outcomes of obese patients with breast cancer. Further research is warranted to elucidate the complex mechanisms linking metabolic imbalance and breast cancer, and to develop innovative strategies that effectively combine metabolic and oncological approaches.

PMID:40593359 | DOI:10.1007/s11033-025-10775-x

Mitigation effect of grape seed extract against cadmium-induced hormonal toxicity in common carp (Cyprinus carpio) - July 2, 2025

BMC Vet Res. 2025 Jul 1;21(1):412. doi: 10.1186/s12917-025-04864-z.

ABSTRACT

BACKGROUND: Cadmium (Cd), a highly toxic heavy metal, poses a significant threat to aquatic organisms by disrupting endocrine and metabolic processes. Its bioaccumulation in fish can impair hormonal regulation, leading to growth suppression, stress, and thyroid dysfunction. Alternative strategies using natural compounds are being explored to mitigate these toxic effects in aquaculture.

OBJECTIVE: In this study, the protective potential of grape (Vitis vinifera L.) seed extract (GSE) against the toxic effects of cadmium (Cd) on growth hormone, stress hormones, and thyroid hormones in common carp (Cyprinus carpio L.) was investigated for the first time.

METHODS: A total of 420 common carp (average weight: 75 ± 5.0 g; average length: 15 ± 2.0 cm) were used, and the experiments were conducted over acute (4 days) and subchronic (30 days) periods. The fish were randomly divided into seven groups, including a control group, a vehicle group (ethanol), a cadmium-only group (20 ppb), two groups receiving GSE alone (5 mg/kg and 10 mg/kg), and two groups receiving cadmium combined with GSE (5 mg/kg and 10 mg/kg). The GSE dosages were calculated based on the body weight of each fish (mg of extract per kg of fish body weight) and administered daily via gavage.

RESULTS: Cadmium exposure caused significant hormonal disruptions in common carp, including reductions in growth hormone, insulin-like growth factor 1, thyroid-stimulating hormone, and triiodothyronine levels, along with elevations in cortisol and thyroxine levels during both acute and subchronic exposure periods (P < 0.05). Grape seed extract treatment mitigated many of these effects, particularly in the acute phase. It improved growth hormone and insulin-like growth factor 1 levels, reduced elevated cortisol concentrations, and notably increased free triiodothyronine levels, thereby contributing to the partial restoration of thyroid hormone balance. However, in the subchronic period, some hormonal disruptions-especially reduced growth hormone levels-persisted despite GSE administration.

CONCLUSIONS: These findings suggest that GSE may serve as a natural protective agent against heavy metal toxicity (Cd) and offer an alternative solution in aquaculture.

PMID:40597059 | PMC:PMC12217834 | DOI:10.1186/s12917-025-04864-z

Pathophysiology and diagnosis of neuroendocrine abnormalities in patients with traumatic brain injury - July 1, 2025

Best Pract Res Clin Endocrinol Metab. 2025 May;39(3):102020. doi: 10.1016/j.beem.2025.102020. Epub 2025 Jun 18.

ABSTRACT

One of the possible clinical complications following traumatic brain injury (TBI) is post-traumatic hypopituitarism. Severe TBI can disrupt the hypothalamus-pituitary-peripheral hormone axes, not only in the acute phase but also over the long term, potentially resulting in persistent pituitary dysfunction. Acute critical illness and its management can alter the normal adaptive response of the hypothalamus-pituitary axis through changes in metabolism, hormone binding, and hormone production. In the context of TBI, structural brain damage may further impair hypothalamus-pituitary function by directly disrupting its anatomical integrity. Diagnosing pituitary hormone imbalances in the acute phase after TBI is challenging, and the clinical significance remains debatable. However, adrenal insufficiency and ADH deficiency poses a life-threatening risk if left untreated and requires prompt intervention. Practical points are provided on how to recognize, avoid, and manage both over- and underdiagnosis of hypopituitarism in patients with TBI.

PMID:40592688 | DOI:10.1016/j.beem.2025.102020

Pirfenidone reduces ovarian fibrosis and improves PCOS in letrozole-induced rat model - June 30, 2025

Biomol Biomed. 2025 Jun 30. doi: 10.17305/bb.2025.12676. Online ahead of print.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by cystic ovarian morphology, anovulation, and infertility. Ovarian fibrosis has recently emerged as a key pathological feature of PCOS. This study investigated whether pirfenidone (PFD), an antifibrotic agent, could improve ovarian dysfunction in a letrozole-induced PCOS rat model. Forty-two female Wistar albino rats were divided into six groups (n=7 each): control, PFD, PCOS, PCOS/PFD, PCOS/combined oral contraceptives (COC), and PCOS/PFD/COC. PCOS was induced using letrozole (1 mg/kg/day orally for 21 days). PFD (200 mg/kg/day) and/or COC (0.18 mg/kg cyproterone acetate and 0.00315 mg/kg ethinyl estradiol) were administered for 21 days. Compared to controls, PCOS rats exhibited significant disruptions in estrous cyclicity, ovarian morphology, and fibrosis-related markers (all p<0.0001), despite no significant changes in testosterone (p=0.058) or estrogen (p=0.896) levels. PFD treatment significantly improved estrous cyclicity, follicular profile, and corpora lutea count (all p<0.0001), reduced ovarian fibrosis (p<0.0001), downregulated TGF-β1, CTGF, and MMP-9 (all p<0.0001), and upregulated PPAR-γ and MMP-2 (both p<0.0001), without affecting hormone levels (p=0.945 and p=0.479, respectively). COC treatment also improved estrous cyclicity and ovarian histology (all p<0.0001), reduced fibrosis (p=0.005), and modulated TGF-β1, CTGF, MMP-9, and PPAR-γ expression (p=0.0001 to <0.0001), but had no effect on MMP-2 (p=0.868). Combination therapy (PCOS/PFD/COC) provided additional improvement in corpora lutea count (p<0.0001 vs. PCOS/PFD) and collagen deposition (p=0.002 vs. PCOS/PFD) but did not confer further benefits in fibrosis-related marker expression or folliculogenesis (all p>0.05). These findings suggest that pirfenidone mitigates PCOS pathology by targeting ovarian fibrosis, supporting antifibrotic therapy as a novel and promising approach.

PMID:40587406 | DOI:10.17305/bb.2025.12676

Emerging pollutants in pharmaceutical and personal care product industrial effluents: Characterization and their environmental impacts - June 30, 2025

Water Sci Technol. 2025 Jun;91(12):1287-1306. doi: 10.2166/wst.2025.073. Epub 2025 May 28.

ABSTRACT

This study aimed to assess emerging pollutants and heavy metals (HMs) in pharmaceuticals and personal care products (PPCPs), industrial effluents, and their environmental impacts using several indices. The mean HM concentrations for pharmaceutical and personal care product (PCP) effluents were in the order of Fe > Ni > Cr > Mn > Pb > Zn > Cu > Cd and Cu > Mn > Cr > Fe > Zn ≥ Pb > Ni > Cd, respectively, where Cr, Ni, Pb, and Cd concentrations for pharmaceutical effluent and Cr, Mn, and Cd for PCP effluent exceeded their accepted limits set by the Department of Environment, Bangladesh 2019. The values of chemical oxygen demand (COD) for PCP effluent were found to be much higher in all seasons, while these values for pharmaceutical effluent slightly exceeded the permissible limits of the Bangladesh Environmental Conservation Rules 2023 in two seasons. The concentrations of nitrate (NO₃^-) and phosphate (PO₄^3-) in both types of effluents were found to be higher in all three seasons. The Pearson correlation matrix and PCA suggested that pH, electrical conductivity, BOD₅, COD, NO₃^-, PO₄^3-, and SO₄^2- were the most correlating and contributing factors. Thirty-seven emerging pollutants, including antibiotics and endocrine-disrupting compounds, were identified in the treated effluent of PPCPs, which have high environmental risk.

PMID:40583486 | DOI:10.2166/wst.2025.073

The Silent Threat of BPA: Its Pervasive Presence and Impact on Reproductive Health - June 30, 2025

Environ Health Insights. 2025 Jun 28;19:11786302251330774. doi: 10.1177/11786302251330774. eCollection 2025.

ABSTRACT

Bisphenol A (BPA) is a synthetic organic compound commonly utilized in the manufacturing of polycarbonate plastics and epoxy resins. Its widespread presence in everyday items, including water bottles, food containers, and thermal paper, has raised considerable health concerns due to its potential as an endocrine disruptor. BPA has the ability to mimic estrogen and bind to estrogen receptors, which can lead to disruptions in hormonal signaling pathways. This interference poses risks to reproductive health, especially among younger individuals, as it may result in irregular menstrual cycles, ovulation issues, and compromised spermatogenesis. Research indicates that BPA exposure can adversely affect ovarian function, diminish sperm quality, and induce oxidative stress and inflammation, further compromising fertility. The potential for BPA to cause long-term health effects through epigenetic modifications, alongside its prevalence in food contact materials, underscores the urgent need for strategies to minimize exposure. Recommended approaches include the use of BPA-free products, choosing fresh foods over canned items, and advocating for stricter regulations. A deeper understanding of the mechanisms underlying BPA's reproductive toxicity is essential for developing effective interventions. Additionally, research is needed to address critical gaps in knowledge regarding the cumulative effects of low-dose exposure, transgenerational impacts, and the specific effects on male fertility. Investigating epigenetic mechanisms, variability in susceptibility, and the safety of BPA alternatives is paramount. Furthermore, exploring effective interventions, increasing public awareness, and implementing regulatory measures are crucial steps in mitigating BPA's adverse effects on reproductive health.

PMID:40584218 | PMC:PMC12206273 | DOI:10.1177/11786302251330774

Relationship between endocrine disruptors and neurodegenerative diseases: Systematic review and meta-analysis - June 30, 2025

iScience. 2025 May 29;28(7):112779. doi: 10.1016/j.isci.2025.112779. eCollection 2025 Jul 18.

ABSTRACT

We conducted a meta-analysis to evaluate relevant literature published between January 2003 and December 2023 in order to provide updated epidemiological evidence on the relationship between endocrine-disrupting chemicals (EDCs) and neurodegenerative diseases (NDs). A systematic search of related studies was conducted in PubMed, Web of Science, and Embase. A total of 21 studies were included, with 286,610 subjects for meta-analysis. Analysis revealed that exposure to polychlorinated biphenyls (odds ratio [OR] = 1.08, 95% confidence interval [CI]: 1.03-1.14) posed a risk for NDs, while organochlorine pesticide (OR = 1.11, 95% CI: 1.05-1.17) exposure exhibited a positive correlation with ND risk. Subgroup analysis by disease indicated a positive association between EDC exposure and Alzheimer's disease (OR = 1.03, 95% CI: 1.00-1.07) and amyotrophic lateral sclerosis (OR = 1.02, 95% CI: 1.01-1.03) risk. Our meta-analysis indicates that human exposure to EDCs has adverse effects on NDs.

PMID:40585363 | PMC:PMC12205615 | DOI:10.1016/j.isci.2025.112779

Integrated Network Toxicology and Experimental Validation Reveal the Mechanism of Bisphenol A-Induced Kidney Injury: Targeting Macrophage Esr1 Expression and Apoptosis - June 30, 2025

J Biochem Mol Toxicol. 2025 Jul;39(7):e70348. doi: 10.1002/jbt.70348.

ABSTRACT

Bisphenol A (BPA), an endocrine-disrupting chemical ubiquitously present in environmental matrices, has emerged as a critical public health concern due to its potential multiorgan toxicity. Although epidemiological and experimental evidence associates BPA exposure with diverse pathologies including metabolic syndrome, carcinogenesis, and hepatorenal dysfunction, the molecular pathogenesis underlying BPA-induced nephrotoxicity remains poorly characterized. To systematically elucidate these mechanisms, we employed an integrative network toxicology approach interrogating multiple pharmacological databases (ChEMBL, STITCH) and disease repositories (GeneCards, OMIM) to identify putative molecular targets. Through rigorous protein-protein interaction network construction (STRING database, Cytoscape), three pivotal hub genes (Esr1, Esr2, Cyp19a1) were prioritized for further investigation. Subsequent multi-omics interrogation encompassed functional enrichment analysis (GO/KEGG), molecular docking simulations, Summary data-based Mendelian randomization (SMR), and immune infiltration analysis. Notably, macrophage-specific Esr1 downregulation was identified as a key molecular event in BPA-exposed renal. Both in vivo and in vitro experiments demonstrated that BPA-mediated Esr1 suppression significantly impaired renal filtration capacity and promoted pro-inflammatory macrophage apoptosis. These findings collectively demonstrate that estrogen receptor alpha (Esr1) serves as a critical molecular nexus linking environmental BPA exposure to macrophage apoptosis-driven renal pathophysiology.

PMID:40586299 | DOI:10.1002/jbt.70348

Estrogenic endocrine disruptors and cancer: a narrative review - June 30, 2025

Endokrynol Pol. 2025;76(3):236-248. doi: 10.5603/ep.104430.

ABSTRACT

Estrogenic endocrine disruptors (e-EDCs) are synthetic or natural compounds present in the environment with the capacity of modulate molecular pathways regulated by estrogen hormones. Scientific evidence suggests a link between e-EDCs exposure and the development of various types of cancers in organs as prostate, breast, cervix, uterus, colon, lung, liver, and others. Interestingly, synthetic and natural e-EDCs role on cancer development include both preventive and promotive mechanisms, that depend on their concentration and exposure period. The molecular action mechanisms of e-EDCs include diverse signaling pathways such as hormone-dependent gene expression, agonism or antagonism of hormone action, among others. This article reviews the studied molecular signaling pathways that underlie the natural and synthetic e-EDCs effects on the development of various types of cancer.

PMID:40586401 | DOI:10.5603/ep.104430

Evaluation of the inhibitory effects of carbamate pesticides on human carboxylesterases - June 30, 2025

Toxicol Appl Pharmacol. 2025 Jun 28:117454. doi: 10.1016/j.taap.2025.117454. Online ahead of print.

ABSTRACT

Carbamate pesticides (CMs), which are widely applied in agricultural production and living environments, have been confirmed to exhibit disruptive effects on lipid metabolism as environmental endocrine disruptors. The present study aims to investigate the inhibition behavior of CMs on the activity of the critical hydrolytic enzymes, carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2), to elucidate the toxicity mechanisms from a novel perspective. Based on network toxicology analysis, CESs were identified as potential targets for CMs-induced lipid metabolism disorders. In vitro incubation experiments demonstrated that most CMs strongly inhibited the activity of CES1 and CES2, with inhibition ratios exceeding 80 %. Kinetic studies and in vitro-in vivo extrapolation revealed that CMs might disrupt the metabolic homeostasis of lipids by inhibiting CESs in vivo. Molecular docking results revealed that hydrogen bonds and hydrophobic contacts formed by ester bonds contributed to the interaction of CMs towards CESs. Cellular fluorescence imaging confirmed the inhibition of CMs on CESs in HepG2 cells. These findings provide new experimental evidence for understanding the mechanism of CMs-mediated lipid metabolism disorders through inhibition on CESs.

PMID:40588104 | DOI:10.1016/j.taap.2025.117454

In utero exposure to a mixture of phthalates, parabens, and other phenols and menstrual cycle characteristics in adolescents - June 30, 2025

Int J Hyg Environ Health. 2025 Jun 29;268:114612. doi: 10.1016/j.ijheh.2025.114612. Online ahead of print.

ABSTRACT

Phthalates, parabens, and other phenols are present in consumer products humans use every day, including personal care products and food packaging. Exposure to these chemicals may have endocrine disrupting effects. The menstrual cycle is guided by the rise and fall of hormones, which may be disrupted by exposure to these chemicals. Urinary concentrations of metabolites of phthalates, parabens, and phenols in mothers during pregnancy and several menstrual cycle characteristics in their daughters at age 16 were examined in a predominantly Latino farmworker cohort. The association between the chemicals and each outcome was examined using logistic regression. Bayesian hierarchical modeling was used to model the chemical mixture's associations with each outcome. All models were adjusted for poverty level during pregnancy, maternal pre-pregnancy BMI, and fast-food consumption at adolescent age 9. Results showed a positive association between mono (3-carboxypropyl) phthalate, propylparaben, and bisphenol-A and heavy menstrual flow. Exposure to 2,4-dichlorophenol was positively associated with short cycle length. Mono(3-carboxypropyl) phthalate and di (2-ethylhexyl) phthalate were positively associated with long cycle length. These results suggest in utero exposure to phthalates, parabens, and other phenols may be associated with abnormal menstrual cycle characteristics in adolescents.

PMID:40587922 | DOI:10.1016/j.ijheh.2025.114612

The effect of vessel noise on behavior and physiology of orange-spotted grouper (Epinephelus coioides) under conditions with and without artificial lighting - June 29, 2025

Mar Pollut Bull. 2025 Jun 28;219:118362. doi: 10.1016/j.marpolbul.2025.118362. Online ahead of print.

ABSTRACT

Anthropogenic disturbances have significantly transformed the ocean soundscape, with vessel noise being a primary factor that overlaps with fish hearing ranges, thereby substantially affecting marine life. Meanwhile, artificial light at night (ALAN) is an emerging stressor that can disrupt the natural rhythms of marine organisms. Despite extensive research on the individual impacts of noise and ALAN, marine organisms are often concurrently exposed to both stressors in natural environments. However, studies on their combined effects remain limited. The orange-spotted grouper (Epinephelus coioides), a large marine bony fish found in tropical and subtropical Pacific-Indian regions and highly sensitive to environmental changes, serves as an excellent model for assessing marine ecological risks. This study employed laboratory simulations to investigate the effects of vessel noise on fish behavior under different lighting conditions (natural light cycles vs. ALAN) over short- (1 week) and long-term (6 weeks) exposures. Transcriptomic analyses of the brain and head kidney were conducted to further explore the physiological impacts. The results indicated that groupers exhibited differential behavioral responses to vessel noise under varying lighting conditions. Transcriptomic data revealed that vessel noise disrupted neural development, immune function, and endocrine regulation. Moreover, the analysis showed that under ALAN, vessel noise had a more pronounced effect on the immune system. Overall, this study demonstrates that vessel noise can disrupt both the behavior and physiology of orange-spotted groupers, underscoring the importance of considering the combined effects of multiple anthropogenic stressors when evaluating their cumulative impacts on marine life.

PMID:40582090 | DOI:10.1016/j.marpolbul.2025.118362

A review of the advances in magnetic solid phase extraction for phthalate analysis: Improved materials and applications in complex matrices - June 29, 2025

Talanta. 2025 Jun 26;296:128519. doi: 10.1016/j.talanta.2025.128519. Online ahead of print.

ABSTRACT

Phthalates (PAEs) are a series of widely used chemicals as plasticizer additives demonstrated to be endocrine disruptors and are detrimental to human health. Different extraction procedures have been used to analyze PAEs in beverages, environmental samples, and food items. These include solid-phase extraction, solid-phase microextraction, magnetic solid-phase extraction (MSPE), and dispersive solid-phase extraction. MSPE is considered to be the most important owing to its easy automation, low consumption of solvents, and super magnetic behavior. In this review, we highlighted the unique characteristics of the MSPE for the enrichment of PAEs. Subsequently, the advanced magnetic composites employed in the MSPE of PAEs have been the subject of extensive discussion. Next, the application of MSPE of PAEs in different complex matrices (environmental, biological, food, and beverages) has been examined. The concluding part has evaluated the possibilities and challenges of the future.

PMID:40582105 | DOI:10.1016/j.talanta.2025.128519

Unveiling the integrated toxicological effects and underlying mechanisms of bisphenol A and cadmium, two hormesis-type endocrine disruptors, on Chromochloris zofingiensis - June 29, 2025

J Hazard Mater. 2025 Jun 26;495:139082. doi: 10.1016/j.jhazmat.2025.139082. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) and cadmium (Cd^{2 +}) are typical endocrine-disrupting compounds (EDCs) that often coexist in aquatic environments and disrupt hormonal pathways, causing adverse effects on organisms. This study showed that both BPA and Cd²⁺ exhibited hormesis effects on Chromochloris zofingiensis, with promoting concentrations of 0.1 mg L^-1 and 0.05 mg L^-1, while inhibiting concentrations of 10 mg L^-1 and 2.5 mg L^-1, respectively. The combination of inhibiting concentrations of BPA and Cd²⁺ significantly elevated intracellular reactive oxygen species level, which resulted in more severe growth inhibition and storage substances accumulation. Additionally, the presence of Cd²⁺ significantly enhanced the degradation rate of BPA by a minimum of 11.8 %, simultaneously shifting the degradation pathway from glycosylation to hydroxylation products. Notably, co-exposure to 0.1 mg L^-1 BPA alleviated the inhibitory effects caused by 2.5 mg L^-1 Cd²⁺, while weakened the promotion effects caused by 0.05 mg L^-1 Cd²⁺. Comparative transcriptome analysis revealed that 0.1 mg L^-1 BPA attenuated Cd²⁺ inhibitory effects by upregulating the expression of the DNA mismatch repair ATPase MLH1 gene involved in mismatch repair. This study provides insights into toxic mechanisms of BPA and Cd²⁺ to microalgae together with their biodegradation patterns, which offers a theoretical basis for the assessment of the risks of coexisted EDCs in the aquatic ecosystems.

PMID:40582152 | DOI:10.1016/j.jhazmat.2025.139082

Diethylhexyl phthalate exposure promotes mitophagy through Drp1-mediated mitochondrial fission in neural crest cells of chick embryos - June 29, 2025

Poult Sci. 2025 Jun 26;104(9):105491. doi: 10.1016/j.psj.2025.105491. Online ahead of print.

ABSTRACT

Di(2-ethylhexyl) phthalate (DEHP) has been used commonly in industrial production and has endocrine disrupting ability. DEHP has potential adverse effects on the development of fetal programming, but the toxic effects and mechanism study in neural crest cells is not enough understood. To investigate DEHP's effects on neural tube closure injury, the chicken embryos and primary cranial neural crest (CNC) cells model of DEHP-treatment was established. Here, we show that the development of neural tube is disrupted by DEHP, which causes an observed decrease in levels of HNK1 and Pax7 and increase in levels of adhesion molecules and extracellular matrix. This led to inhibit the migration and epithelial-mesenchymal transition (EMT) mechanism in neural crest cells, which cause dysraphism in chicken embryos. Furthermore, DEHP exposure also disrupts mitochondrial function accompanied by the elevation of Drp1 and FIS1 level, and the decrease of MFN1, MFN2, and OPA1 level, causing excessive mitochondrial fragmentation, mitophagy and apoptosis, eventually decreasing the MMP levels and ATP concentration in chicken embryos. Conversely, the addition of Drp1 inhibitor dramatically alleviate the mitochondrial fragmentation and mitophagy induced by DEHP in primary CNC cells. Our results reveal the mechanism of DEHP-induced mitophagy in neural crest cells was regulated by excessive activation of Drp1-mediated mitochondrial fission. These findings deepen the research of reproductive toxicology of DEHP and guide its application in different areas, especially in the agricultural field.

PMID:40582160 | DOI:10.1016/j.psj.2025.105491

Distinguishing immune checkpoint inhibitor-induced hypothyroid myopathy from myositis: a case report and review - June 29, 2025

Neuromuscul Disord. 2025 Jun 16;52:105420. doi: 10.1016/j.nmd.2025.105420. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, they can induce immune-related adverse events (irAEs), including hypothyroidism, the most common endocrine irAE. ICI-induced hypothyroid myopathy (ir-HM) is a rare condition that can be mistaken for ICI-induced myositis (ir-myositis). We encountered a case of ir-HM that was similar to ir-myositis. A 72-year-old male with lung cancer developed hypothyroidism and myopathy 21 weeks after initiating pembrolizumab treatment. Muscle biopsy revealed myofibrillar network disruption without inflammatory changes. A literature review identified 9 ir-HM cases, typically occurring more than 2 months after the initiation of ICI therapy. Key distinctions between ir-HM and ir-myositis include onset time, treatment approach, and the presence of the myoedema. Proper diagnosis of ir-HM is crucial for appropriate management, potentially allowing continuation of ICI therapy. This study highlights the importance of considering ir-HM in patients with myopathy symptoms occurring a longer period after the initiation of ICI treatment.

PMID:40582338 | DOI:10.1016/j.nmd.2025.105420

Biodegradation of progesterone and norgestrel in wastewater by functional bacterial gels: Perspectives from simultaneous reduction of transformation products and endocrine disrupting effects - June 29, 2025

Bioresour Technol. 2025 Jun 27:132911. doi: 10.1016/j.biortech.2025.132911. Online ahead of print.

ABSTRACT

The steroidal progestogens have attracted much attention on their occurrence and fate in wastewater due to their endocrine disrupting effects to aquatic organisms at ng/L levels. Enhanced removal of progestogens by functional bacteria is an environmental-friendly and low-cost technology. However, the effectiveness of the immobilized functional bacteria in simultaneously removing target progestogens, their transformation products (TPs) and endocrine-disrupting risks in wastewater has not been well documented. This study isolated three strains of functional bacteria that can effectively degrade two typical progestogens, progesterone (P4) and norgestrel (NGT), immobilized the bacteria into bacterial gels and constructed the bacterial gels reactor (BGR). Batch experiment showed that the biodegradation of P4 and NGT by the bacterial gels followed first-order kinetics, with kinetic constants of 0.09 and 0.08 h^-1, respectively, and 11 and 12 TPs of P4 and NGT were identified by using high resolution mass spectrometry. The BGR was effective in removing P4 and NGT in long-time operating, with removal efficiencies of 99.3 % and 97.1 %, respectively. Further, the BGR was connected in series behind an A/A/O reactor. The long-time operating results showed that the BGR further enhanced P4 (62 %) and NGT (50 %) removal in the A/A/O secondary effluent, with simultaneously reducing the adverse effects of the effluent on transcripts of the zebrafish gonads. Additionally, relative abundances of most TPs were also reduced by the BGR. This study demonstrated the effectiveness of bacterial gels in simultaneously removing P4/NGT, TPs and endocrine disrupting risks in wastewater.

PMID:40582423 | DOI:10.1016/j.biortech.2025.132911

Exposure to "Forever Chemical" perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis - June 28, 2025

Environ Int. 2025 Jun 23;202:109631. doi: 10.1016/j.envint.2025.109631. Online ahead of print.

ABSTRACT

Perfluorooctanoic acid (PFOA), an environmental endocrine disruptor, has been found to increase the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN). In this study, adult male mice were given PFOA by oral gavage (p.o.) to evaluate whether it disrupts systems related to mood disorders. PFOA exposure (5 mg/kg) for 10 consecutive days caused depression-like behaviors in male mice. We measured increased corticosterone in serum and in the hippocampus of PFOA-exposed mice, which were linked to enhanced CRF expression measured in the PVN. Elevated corticosterone was associated with reductions in glucocorticoid receptor (GR) protein expression within the hippocampus. CRFR1 antagonist injected into the PVN and intracerebroventricular (i.c.v.) GR antagonist both reduced depression-like behaviors, respectively. In addition, NMDA-dependent Schaeffer collateral-CA3 synaptic transmission in PFOA-exposed mice was disrupted. Synaptic deficits could be corrected by either CRFR1 or GR antagonists. In summary, we found exposure of male mice to PFOA enhances CRF expression, which then activates the HPA axis to disrupt GR expression in the hippocampus, leading to depression-like behaviors. This data is relevant for understanding the potential harmful health effects of PFOA.

PMID:40580708 | DOI:10.1016/j.envint.2025.109631

Pembrolizumab-Induced Hypothyroidism and Diabetes Mellitus: A Rare Case Presentation Post-Treatment - June 27, 2025

Cureus. 2025 May 27;17(5):e84880. doi: 10.7759/cureus.84880. eCollection 2025 May.

ABSTRACT

Pembrolizumab is a humanized monoclonal antibody that targets programmed death-1 (PD-1), a cell surface receptor expressed on activated T lymphocytes. By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, pembrolizumab enhances T-cell-mediated immune responses against tumor cells. This immunotherapeutic strategy has shown significant clinical benefit in a range of malignancies, including metastatic melanoma, non-small cell lung cancer, and renal cell carcinoma. However, its mechanism of action can also disrupt immune self-tolerance, leading to immune-related adverse events (irAEs), particularly involving endocrine organs. These irAEs may manifest as autoimmune thyroiditis, hypophysitis, or, more rarely, insulin-dependent diabetes mellitus. In this case, the patient presented to a rural district general hospital with a several-week history of fatigue, polydipsia, and polyuria approximately two months after completing a one-year course of pembrolizumab for metastatic melanoma. Given the delayed and nonspecific symptom onset, diagnosis required a high degree of clinical suspicion. Laboratory investigations revealed severe hyperglycemia, suppressed C-peptide levels, and abnormal thyroid function tests. These findings were consistent with pembrolizumab-induced type 1 diabetes mellitus and hypothyroidism, both of which are recognized, though uncommon, endocrine irAEs.

PMID:40575214 | PMC:PMC12199207 | DOI:10.7759/cureus.84880

The effects of radiation therapy on the brain: implications for management - June 27, 2025

Chin Clin Oncol. 2025 Jun;14(3):32. doi: 10.21037/cco-24-125. Epub 2025 Jun 10.

ABSTRACT

Radiation therapy (RT) plays a critical role in the management of intracranial malignancies, offering a potent and targeted approach to tumor control. The benefits of RT have been recognized for decades, and it is commonly employed in the management of both primary brain tumors and, especially, brain metastases. Through the induction of DNA damage and disruption of cellular integrity, RT promotes apoptosis and inhibits the proliferative capacity of cancer cells. Advances in imaging, dose planning, and delivery techniques have significantly enhanced the precision of RT, allowing for effective tumor eradication while minimizing harm to surrounding healthy tissue. As a result, RT improves local disease control and contributes to prolonged survival in patients with brain tumors. Nonetheless, intracranial RT may inadvertently damage surrounding healthy brain structures. The effects of RT can manifest as both acute and delayed toxicities, potentially compromising patient quality of life and long-term outcomes. For treating clinicians, a thorough understanding of these complications is necessary to design radiation treatment plans that properly balance the therapeutic efficacy of therapy with the risks of adverse treatment-related outcomes. In this review, we explore the distinct pathophysiological mechanisms, symptoms, and management strategies associated with acute, early delayed (one to six months), and late delayed radiation-induced brain toxicities. In particular, we discuss the risks of somnolence syndrome, peri-ictal pseudoprogression, radiation necrosis, vascular disorders, cognitive impairment, cranial neuropathies, endocrine dysfunction, the development of secondary malignancies, stroke-like migraine attacks after radiation therapy (SMART) syndrome, and acute late-onset encephalopathy after radiation therapy (ALERT) syndrome after brain RT.

PMID:40575969 | DOI:10.21037/cco-24-125

Genomic evidence based on EQTL data implicates endocrine disruptors as environmental risk factors for estrogen receptor-positive breast cancer - June 27, 2025

Int J Surg. 2025 Jun 27. doi: 10.1097/JS9.0000000000002642. Online ahead of print.

ABSTRACT

BACKGROUND: Estrogen receptor-positive (ER +) breast cancer is the most common molecular subtype of breast cancer and is strongly influenced by hormonal and environmental factors. Endocrine-disrupting chemicals (EDCs), which interfere with hormone signaling, have been suggested to contribute to ER + breast cancer risk, but causal mechanisms remain unclear.

METHODS: We integrated chemical-gene interaction data from the TEDX and CTD databases with large-scale genomic datasets to investigate the relationship between EDC-regulated gene expression and ER + breast cancer. A total of 5,797 EDC-related genes were identified and filtered using cis-expression quantitative trait loci (cis-eQTL) data from eQTLGen. Mendelian randomization (MR) and colocalization analyses were performed using ER + breast cancer GWAS summary statistics to assess causal associations and shared genetic signals. Interacting EDCs were mapped to colocalized genes.

RESULTS: Among 4,207 genes with available cis-eQTLs, 50 showed statistically significant associations (FDR < 0.05) with ER + breast cancer. Of these, 24 genes, including CIRBP, JMJD1C, and TET2, demonstrated strong evidence of colocalization. Key EDCs, such as bisphenol A and phthalates, were identified to interact with multiple high-risk genes, suggesting potential environmental drivers of ER + breast cancer.

CONCLUSION: This study provides genetic evidence supporting the causal role of EDC-regulated gene expression in ER + breast cancer. The integration of MR, colocalization, and chemical-gene networks offers a novel framework for identifying environmentally relevant risk factors and contributes to understanding the gene-environment mechanisms underlying hormone-dependent cancers.

PMID:40576180 | DOI:10.1097/JS9.0000000000002642

Typical Thermochromic Dye Crystal Violet Lactone Acts as an Endocrine Disruptor: Nontargeted Screening, Prioritization, and In Vivo Experimental Verification - June 27, 2025

Environ Sci Technol. 2025 Jun 27. doi: 10.1021/acs.est.5c04123. Online ahead of print.

ABSTRACT

Identification and characterization of endocrine disruptors and their associated ecological and health risks are critical areas of environmental toxicology. In this study, we aimed to identify previously unrecognized endocrine disruptors in thermal paper by employing a nontargeted screening coupled ToxPi Ranking (NSTR) approach. Among the substances identified with high confidence in thermal paper, Crystal Violet Lactone (CVL), a typical thermochromic dye, was prioritized with a high endocrine disruptive potential. CVL can be absorbed through the skin and excreted in the urine. In addition, we demonstrated significant bioaccumulation of CVL in zebrafish tissues, with hepatic concentrations reaching up to 3.1 times those in the exposure water, and five biotransformation products were identified. CVL exposure impaired the reproductive capacity of breeding pairs, led to gonadal histological alterations, and exhibited developmental toxicity to F1 offspring. Transcriptional analysis revealed disruptions in the expression of hypothalamic-pituitary-gonad-liver (HPG-L) axis genes in adults. In embryos, CVL significantly increased the frequency of epiboly, yolk extension formation, and somite number while decreasing the ear-eye distance and size of the yolk sac. Significant alterations in HPG-L axis genes were observed, as well. Thus, our data demonstrated that CVL targeted multiple end points in both adult fish and embryos, exhibiting remarkably endocrine disruptive effects.

PMID:40576419 | DOI:10.1021/acs.est.5c04123

Assessing the impact of 4-nonylphenol and 17beta-estradiol on growth, steroidogenesis and vitellogenin expression in juvenile manila clams: Implications for endocrine disruption - June 27, 2025

Mar Environ Res. 2025 Jun 18;210:107303. doi: 10.1016/j.marenvres.2025.107303. Online ahead of print.

ABSTRACT

The contamination of marine sediments by endocrine-disruptive contaminants (EDCs) represents a global threat to marine ecosystems. Among these pollutants, 4-nonylphenol (4-NP) and 17β-estradiol (E2) are particularly noted for their potent endocrine-disrupting effects in aquatic organisms. This study employed juvenile Manila clams (Ruditapes philippinarum), with genetically determined sexes, as model organisms in a 14-day exposure experiment. The clams were exposed to 4-NP and E2 at concentrations of 0 (control), 0.1, 1, and 10 μg/L. We primarily investigated the effects on steroidogenesis and vitellogenin (VTG) expression, which are key factors in assessing endocrine disruption. Results showed that 4-NP inhibited shell growth at all tested concentrations, and increased free E2 in tissues levels were observed in clams exposed to 0.1 μg/L of 4-NP on both the 7th and 14th days. Conversely, E2 did not significantly affect free E2 in tissues levels. Notably, exposure to 1 μg/L 4-NP significantly upregulated mRNA expression of genes involved in the steroidogenesis pathway (GnRH, CYP17, and 17β-HSD) in genetically female juveniles. Both male and female juveniles showed increased VTG mRNA expression after 4-NP exposure. These findings confirm the endocrine-disrupting potential of 4-NP, particularly affecting genetically female juveniles. The alterations in key genes involved in steroidogenesis and the upregulation of VTG expression highlight the vulnerability of bivalves to EDCs. This study underscores the importance of VTG expression as a reliable biomarker for assessing the estrogenic impacts and action mechanisms of EDCs in juvenile bivalves.

PMID:40577888 | DOI:10.1016/j.marenvres.2025.107303

Dietary patterns and exposure to non-persistent endocrine-disrupting chemicals during pregnancy - June 27, 2025

Environ Int. 2025 Jun 16;202:109612. doi: 10.1016/j.envint.2025.109612. Online ahead of print.

ABSTRACT

BACKGROUND: Exposure to non-persistent endocrine disrupting chemicals (EDCs) is widespread, causing various adverse health effects, especially during pregnancy. Diet is a major source of EDCs and the identification of dietary patterns that give rise to higher exposure levels is crucial. We aimed to explore the relationship between dietary patterns during pregnancy and exposure to non-persistent EDCs.

METHODS: We included 640 pregnant women from the Barcelona Life Study Cohort (BiSC), Spain. Using food frequency questionnaires (2nd trimester), we estimated ultraprocessed food (UPF) consumption and Mediterranean diet adherence, and derived data-driven dietary patterns. Metabolites of phthalates, 1,2-cyclohexane dicarboxylic acid di(isononyl) ester (DINCH), chlorpyrifos and pyrethroid, polycyclic aromatic hydrocarbons (PAHs, including phenanthrenes), and organophosphates, and parent compounds of phenols and parabens were measured in weekly urine pools (3rd trimester). Associations between dietary patterns and EDCs were evaluated through multivariable linear regressions.

RESULTS: Higher compliance with a "Vegetarian" pattern or the Mediterranean diet was associated with lower levels of some of the phthalate metabolites (e.g., di-iso-nonyl phthalates [Geometric mean ratio (GMR) per unit increases in the "Vegetarian" score = 0.97, 95 %CI 0.95, 1.00]). Conversely, "Western" and "Animal protein" patterns, and UPF intake were associated with higher PAHs (e.g., "Western" and 2-Hydroxynaphthalene [GMR(95 %CI) 1.07(1.01, 1.13)]), pesticides (e.g., "Animal protein" and 3-Phenoxybenzoic acid [1.15(1.01, 1.32]), and phthalates metabolites levels (e.g., UPF and Monoethyl phthalate [1.05(1.01, 1.09)]). No association remained significant after correcting for multiple testing.

CONCLUSIONS: Following a plant-based diet may help reduce the exposure to certain phthalate and organophosphate metabolites, whereas higher consumption of foods from animal origin and high in fat/sugar/salt may increase exposure to PAHs, pesticides, and phthalates metabolites in pregnancy.

PMID:40578114 | DOI:10.1016/j.envint.2025.109612

Assessing polylactic acid (PLA) fiber safety using underwear paddings as a model via nontargeted screening and toxicological risk scoring - June 27, 2025

J Hazard Mater. 2025 Jun 24;495:139046. doi: 10.1016/j.jhazmat.2025.139046. Online ahead of print.

ABSTRACT

Polylactic acid (PLA) fabrics made from PLA fibers are increasingly being promoted. However, the potential health risks of wearing PLA fabrics remain under explored. This study simulates the washing and drying cycles of underwear with PLA paddings and investigates the leaching of chemical additives in artificial sweat, with the aim of evaluating the exposure concentration levels of various additives in PLA fabrics during wear, subjected to different degrees of mechanical stress. Through nontargeted analysis, 70 chemicals were identified. The Toxicological Prioritization Index (ToxPi) was employed to score and rank the toxicity of these chemicals, parameters associated with skin stimulation were highlighted. Fourteen chemicals with higher toxicity scores and two phthalate esters (PAEs) as representatives of endocrine disrupting chemicals, were selected for quantitative analysis of leachates. The results indicated the presence of significant quantities of these chemicals in all samples, with total amounts ranging from 40.0 to 120 μg/g. The five chemicals with the highest leaching amounts-trifluoroacetic acid, tri-n-butyl phosphate, 2,6-di-tert-butylphenol, bis(2-ethylhexyl) phthalate, and 4-dodecylbenzenesulfonic acid-showed maximum leaching amounts of 51.2 μg/g, 49.6 μg/g, 26.1 μg/g, 16.7 μg/g, and 12.6 μg/g, respectively. Furthermore, considerable differences in exudation patterns were observed among the various chemicals. According to health risk assessment conducted by ToxPi, several chemicals have high toxicity weighted concentrations, suggesting the potential health risk of PLA fabrics. This study found that PLA fibers contain various toxic additives, and as the human body comes into more contact with PLA fibers, the exposure levels of these chemicals may pose health hazards and calls for a comprehensive evaluation of the environmental and health risks associated with PLA fiber products.

PMID:40578205 | DOI:10.1016/j.jhazmat.2025.139046

Comprehensive assessment of natural estrogens in poultry eggs: Implications for health risks and dietary intervention strategies - June 27, 2025

Food Chem Toxicol. 2025 Jun 25;203:115607. doi: 10.1016/j.fct.2025.115607. Online ahead of print.

ABSTRACT

Poultry eggs are a dietary staple in China, yet their natural estrogen (NE) content remains largely unexplored. This study developed a method to detect 12 NEs in chicken, duck, quail, and pigeon eggs. Eleven NEs were detected in at least one sample, with concentrations of 1.66-15.7 ng/g. Total NEs were highest in duck eggs, followed by chicken eggs, while quail and pigeon eggs had similar levels. The estimated daily intake was highest for duck eggs (3.32 ng/kg bw/d), followed by chicken eggs (3.09 ng/kg bw/d) and quail/pigeon eggs (1.56 ng/kg bw/d). Estrogen equivalents indicated that duck eggs posed the greatest risk. Four common NEs exceeded the children's safety threshold of 0.1 ngE2/d/person, and the less-studied metabolites 16/17epiE3 levels exceeded this value by 3-/6-fold. Library Docking (LibDock) scores and 2D-QSAR analysis identified 16/17epiE3 as the most harmful to children's health. Supplementation with vitamins B2 and B12 significantly reduced the LibDock scores of 16/17epiE3, suggesting a potential strategy to mitigate their estrogenic effects. This pioneering study assesses emerging endocrine-disrupting compounds, NEs in poultry eggs, emphasizing the importance of addressing less-studied NEs. These findings enhance food safety measures to protect public health, and research on NEs in animal foods.

PMID:40578475 | DOI:10.1016/j.fct.2025.115607

Association between in utero exposure to organochlorine pesticides and steroids in cord blood - June 27, 2025

Environ Pollut. 2025 Jun 25;382:126727. doi: 10.1016/j.envpol.2025.126727. Online ahead of print.

ABSTRACT

Organochlorine pesticides (OCPs) are endocrine disruptors, and previous studies have shown that OCPs exposure is associated with hormone levels in the general population. However, there is limited evidence regarding the effects of prenatal OCPs exposure on steroid concentrations in offspring. To explore the association between prenatal OCPs exposure and offspring steroid levels, we designed a cross-sectional study including 981 mother-infant pairs. Cord serum concentrations of dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH) and steroids were measured. Multiple linear regression models were used to examine the relationships between OCPs exposure and steroids levels in cord blood. Restricted cubic spline (RCS) models were used to assess the dose-response relationships between selected OCPs and steroids. Results showed that OCPs exposure was associated with decreased steroids levels of newborns and the associations were dose-dependent. Specifically, we found that estradiol decreased by 11.17 % (95 % CI: -16.95 %, -4.99 %) and 9.28 % (95 % CI: -14.94 %, -3.24 %) with each 10-fold increase in β-HCH and p,p'-DDE, respectively. Cortisol decreased by 14.99 % (95 % CI: -23.19 %, -5.93 %) with each 10-fold increase in p,p'-DDE. Furthermore, these associations were more pronounced in male infants and those born by cesarean section. In conclusion, this study presented robust disrupting effects of β-HCH and p,p'-DDE exposure on estradiol and cortisol.

PMID:40578747 | DOI:10.1016/j.envpol.2025.126727

Profiles of Circulating Exosomal microRNAs in Female College Students with Qi Stagnation and Balanced Constitutions by High-Throughput Sequencing - June 27, 2025

Comb Chem High Throughput Screen. 2025 Jun 25. doi: 10.2174/0113862073399668250612045822. Online ahead of print.

ABSTRACT

INTRODUCTION: Individual constitutions are classified into nine types in traditional Chinese medical theory, and qi stagnation constitution (QSC) manifests as disrupted Qi circulation and increased susceptibility to emotional disorders and cancers. However, as a pre-disease state mainly affecting women, the biological basis of QSC and its susceptible mechanism to related diseases are still unclear. Exosomal microRNAs (miRNAs) are the stable regulators of gene expression and intercellular communication, and analysis of miRNAs enables us to understand the QSC better. This study profiles plasma exosomal miRNAs in QSC and balanced constitution (BC) females via high-throughput sequencing, aiming to identify the potential biomarkers of QSC and reveal its biological basis and the mechanism of its susceptible disease.

METHODS: In this cross-sectional observation, female college students were recruited according to the criterion of QSC and BC in Classification and Determination of Constitution in TCM. Exosomal miRNAs were isolated from blood plasma and then profiled using high-throughput sequencing. Differentially expressed miRNAs (DEMs) were identified with fold change > 2 and P < 0.05, and screened as biomarkers to construct the receiver operating characteristic (ROC) curve. The diagnostic values of these biomarkers in different types of cancers were also validated based on the published data. KEGG and GO functional analysis were explored based on the predicted target genes.

RESULTS: Subjects with QSC showed significantly higher concentrations of albumin (ALB) and alkaline phosphatase (ALP) compared to those with BC, while there was no significant difference in baseline information and other clinical indicators between groups. A total of 54 DEMs were identified, including 30 30 up-regulated and 24 down-regulated miRNAs in the QSC group. The area under the ROC curve (AUC) for 7 specific up-regulated DEMs was 1.0, as well as the AUCs for therein 6 DEMs in various cancers were all above 0.9. The enriched KEGG pathways included "signal transduction," "infectious disease," and "cancers", and the most associating systems included immune, endocrine, and nervous systems, while the GO function was mainly enriched in "protein binding," "nucleus" and "transcription, DNA-templated".

DISCUSSION: These 7 potential biomarkers of QSC have been confirmed to regulate oncogenic processes through epithelial-mesenchymal transition modulation and metabolic reprogramming, as well as therein 1 can also improve depression by lowering the expression of 5-hydroxytryptamine 1A receptor. The results of this study deepen the understanding of the traditional Chinese medicine constitutions. However, the small single-sex sample limits the application of the conclusion, and a large-scale clinical cohort including both sexes is still needed in future.

CONCLUSION: The expression of exosomal miRNAs in QSC showed unique features that have the potential to serve as biomarkers, and the related functional changes might be the biological basis for the susceptible diseases of QSC.

PMID:40574361 | DOI:10.2174/0113862073399668250612045822

Outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for bifenazate in light of confirmatory information on the endocrine disruption assessment - June 26, 2025

The European Food Safety Authority (EFSA) was asked by the European Commission to provide scientific assistance with respect to the risk assessment for an active substance in light of confirmatory information requested following approval in accordance with Article 6(1) of Directive 91/414/EEC and Article 6(f) of Regulation (EC) No 1107/2009.

Structural and Hormonal Changes in Reproductive-Age Women Post-COVID-19: A Cross-Sectional Ultrasound and Biochemical Study - June 26, 2025

Diagnostics (Basel). 2025 Jun 17;15(12):1536. doi: 10.3390/diagnostics15121536.

ABSTRACT

Background/Objectives: The long-term impact of COVID-19 on female reproductive health remains poorly understood. This study aimed to assess structural and endocrine alterations in women of reproductive age who had recovered from SARS-CoV-2 infection compared to uninfected controls. Materials and Methods: A total of 150 women aged 18-45 years were enrolled in a comparative study: 75 with a confirmed history of COVID-19 and 75 without one. All participants underwent ultrasound examinations of their pelvic organs and mammary glands, along with laboratory assessment of reproductive hormones and inflammatory markers. Results: Structural abnormalities in the pelvic organs were observed in 53.5% of the post-COVID-19 group versus 12.0% of the control group (p < 0.001), with oophoritis showing a statistically significant association (OR = 11.38; 95% CI: 1.42-91.36; p = 0.009). Non-significant but elevated frequencies were also found for uterine fibroids and breast cysts. Biochemically, post-COVID-19 participants demonstrated higher serum ferritin, estradiol, and fibrinogen levels, along with lower TSH and AMH levels, suggesting potential endocrine disruption and persistent inflammation. Conclusions: Women with a history of COVID-19 may be at increased risk of developing structural and hormonal abnormalities, highlighting the importance of post-infection gynecological and endocrine monitoring. Further longitudinal studies are required to elucidate the long-term effects and underlying mechanisms of these alterations.

PMID:40564856 | PMC:PMC12192474 | DOI:10.3390/diagnostics15121536

RNA-Seq Uncovers Association of Endocrine-Disrupting Chemicals with Hub Genes and Transcription Factors in Aggressive Prostate Cancer - June 26, 2025

Int J Mol Sci. 2025 Jun 6;26(12):5463. doi: 10.3390/ijms26125463.

ABSTRACT

This study analyzes publicly available RNA-seq data to comprehensively include the complex heterogeneity of prostate cancer (PCa) etiology. It combines prostate and prostate cancer (PCa) cell lines, representing primary PCa cells, Gleason scores, ages, and PCa of different racial origins. Additionally, some cell lines were exposed to endocrine-disrupting chemicals (EDCs). The research aims to identify hub genes and transcription factors (TFs) of the prostate carcinogenesis pathway as molecular targets for clinical investigations to elucidate EDC-induced aggressiveness and to develop potential biomarkers for their exposure risk assessments. PCa cells rely on androgen receptor (AR)-mediated signaling to survive, develop, and function. Fifteen various RNA-seq datasets were normalized for distribution, and the significance (p-value < 0.05) threshold of differentially expressed genes (DEGs) was set based on |log2FC| ≥ 2 change. Through integrated bioinformatics, we applied cBioPortal, UCSC-Xena, TIMER2.0, and TRRUST platforms, among others, to associate hub genes and their TFs based on their biologically meaningful roles in aggressive prostate carcinogenesis. Among all RNA-Seq datasets, we found 75 overlapping DEGs, with BUB1B (32%) and CCNB1 (29%) genes exhibiting the highest degree of mutation, amplification, and deletion. EDC-associated CCNB1, BUB1B, and CCNA2 in PCa cells exposed to EDCs were consistently shown to be associated with high Gleason scores (≥4 + 3) and in the >60 age group of patients. Selected TFs (E2F4, MYC, and YBX1) were also significantly associated with DEGs (NCAPG, MKI67, CCNA2, CCNB1, CDK1, CCNB2, AURKA, UBE2C, BUB1B) and influenced the overall survival (p-value < 0.05) of PCa cases. This is one of the first comprehensive studies combining 15 publicly available RNA-seq datasets to demonstrate the association of EDC-associated hub genes and their TFs aligning with the aggressive carcinogenic pathways in the higher age group (>60 years) of patients. The findings highlight the potential of these hub genes as candidates for further studies to develop molecular biomarkers for assessing the EDC-related PCa risk, diagnosing PCa aggressiveness, and identifying therapeutic targets.

PMID:40564927 | PMC:PMC12192892 | DOI:10.3390/ijms26125463

Coenzyme Q10 and Xenobiotic Metabolism: An Overview - June 26, 2025

Int J Mol Sci. 2025 Jun 17;26(12):5788. doi: 10.3390/ijms26125788.

ABSTRACT

Mitochondria are primary targets for environmental toxic chemicals; these typically disrupt the mitochondrial electron transport chain, resulting in reduced ATP production, increased reactive oxygen free radical species (ROS)-induced oxidative stress, increased apoptosis, and increased inflammation. This in turn suggests a rationale for investigating the potential role of coenzyme Q10 (CoQ10) in mediating such chemical-induced mitochondrial dysfunction, given the key roles of CoQ10 in promoting normal mitochondrial function, and as an antioxidant and anti-apoptotic and anti-inflammatory agent. In the present article, we have, therefore, reviewed the potential role of supplementary CoQ10 in improving mitochondrial function and mediating adverse effects following exposure to a number of environmental toxins, including pesticides, heavy metals, industrial solvents, endocrine-disrupting agents, and carcinogens, as well as pharmacological drugs and lifestyle toxicants.

PMID:40565253 | PMC:PMC12193255 | DOI:10.3390/ijms26125788

Endocrine and Metabolic Mechanisms Linking Obesity to Type 2 Diabetes: Implications for Targeted Therapy - June 26, 2025

Healthcare (Basel). 2025 Jun 16;13(12):1437. doi: 10.3390/healthcare13121437.

ABSTRACT

Obesity and Type 2 Diabetes Mellitus (T2DM) are interrelated chronic conditions whose global prevalence continues to rise, posing significant clinical and socioeconomic challenges. Their pathophysiological intersection-commonly referred to as "diabesity"-is sustained by a complex interplay of mechanisms, including visceral adipose tissue inflammation, macrophage polarization, disrupted insulin signaling, and adipokine imbalance. These processes contribute to chronic low-grade systemic inflammation, impair pancreatic β-cell function, and exacerbate glucose intolerance. This review critically explores the mechanistic connections between obesity and T2DM, with a focus on recent advances in pharmacological therapies-such as GLP-1 receptor agonists, SGLT2 inhibitors, and dual GIP/GLP-1 receptor agonists-alongside evidence-based lifestyle modifications and bariatric procedures. By integrating current translational and clinical findings, we aim to provide a comprehensive perspective to support the development of more effective and individualized treatment strategies for diabesity.

PMID:40565464 | PMC:PMC12193533 | DOI:10.3390/healthcare13121437

Distribution and Health Risk Assessment of Triclosan and Other Typical Endocrine Disruptors in Honey - June 26, 2025

Foods. 2025 Jun 6;14(12):2006. doi: 10.3390/foods14122006.

ABSTRACT

Endocrine disruptors (EDCs) in food pose a significant threat to health. This study developed a method for detecting seven EDCs (triclosan (TCS), triclocarban (TCC), methyltriclosan (MTCS), methylparaben (MeP), propylparaben (PrP), bisphenol F (BPF), and 4-hydroxybenzophenone-3-ethylcarboxylate (4HBP)) in honey. The method combines ultrasonic-assisted dispersive liquid-liquid microextraction with high-performance liquid chromatography. It achieved a recovery rate of 89.70-102.2%, with an RSD value of 1.1-3.9%. Additionally, this study tested 47 honey samples from seven countries, revealing detection rates of TCS at 29.79%, TCC at 19.15%, BPF at 97.87%, 4HBP at 36.17%, MeP at 82.98%, and PrP at 80.85%. Among the 12 nectar sources, citrus flower nectar had the highest TCS detection rate, mother grass nectar had the highest TCC detection rate, and multi-flower nectar had the highest 4HBP detection rate. Moreover, imported honey samples showed higher levels of TCS, BPF, and MeP contamination compared to domestic samples. Honey stored in PET bottles contained the highest levels of EDCs. Finally, health risk assessments indicated that, while the risk for adults is lower, monitoring EDC contamination in food should be strengthened to ensure consumer safety.

PMID:40565615 | PMC:PMC12191833 | DOI:10.3390/foods14122006

A Temporal Single-Cell Multi-Omics Atlas of Murine Pancreatic Islet Remodeling During Hyperglycaemia Progression - June 26, 2025

bioRxiv [Preprint]. 2025 Jun 1:2025.05.29.656754. doi: 10.1101/2025.05.29.656754.

ABSTRACT

Pancreatic islets undergo coordinated cellular remodeling during obesity-induced insulin resistance (IR). However, the associated molecular changes across endocrine and non-endocrine compartments remain largely unexplored. Here, using longitudinal single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on islets from C57BL/6 mice subjected to high-fat diet (HFD) feeding for 8, 16, and 24 weeks, along with age-matched controls on regular chow, we mapped dynamic changes in islet cell composition and transcriptional states. Beta cells demonstrated pronounced stress-induced reprogramming, with the emergence of proliferative and dysfunctional subsets. Alpha and delta cell fractions declined under HFD, despite increased polyhormonal biosynthesis, suggesting functional rather than numerical adaptation. Immune profiling showed robust expansion of proinflammatory M1 macrophages and upregulation of NF-κB and chemotaxis pathways, particularly at 16 weeks. Notably, cell-cell communication analyses revealed diet-specific disruption in signaling networks. Under HFD conditions, intercellular communication among beta cells, macrophages, and delta cells was markedly altered, leading to the disruption of key signaling pathways such as the gastric inhibitory polypeptide receptor (GIPR) and major histocompatibility complex-I (MHC-I). Notably, C-C motif chemokine ligand 27A ( Ccl27a ) expression and chromatin accessibility were significantly altered in a distinct subpopulation of beta cells under HFD condition, indicative of a niche-specific regulatory mechanism. Integration with human islet datasets from obese and type 2 diabetes (T2D) donors confirmed conserved shifts in beta cell identity and immune activation. This study presents a comprehensive high-resolution atlas of islet remodeling under metabolic stress, identifying key communication nodes and transcriptional programs pertinent to T2D pathogenesis.

PMID:40568114 | PMC:PMC12190480 | DOI:10.1101/2025.05.29.656754

The Interplay Between Body Weight and the Onset of Puberty - June 26, 2025

Children (Basel). 2025 May 25;12(6):679. doi: 10.3390/children12060679.

ABSTRACT

This overview explores the complex relationship between environmental factors, particularly obesity, and the timing of puberty, with a focus on how hormonal and genetic interactions are influenced by external conditions. Puberty (gonadarche) is characterised by the activation of the hypothalamic-pituitary-gonadal (HPG) axis. The onset and progression of puberty vary significantly among individuals, primarily due to genetic factors, with key genes like kisspeptin 1 (KISS1) and makorin ring finger protein 3 (MKRN3) playing a crucial role. Cohesively, this paper emphasises that environmental factors, particularly obesity and exposure to endocrine-disrupting chemicals (EDCs), have become significant influences on the timing of puberty. Childhood obesity has risen significantly in recent decades and the age of pubertal onset has declined over the same period. Obesity greatly disrupts hormone regulation in pre-pubertal children. Leptin accelerates the onset of puberty in girls but not in boys. The underlying mechanism is proposed to be the increase in Kiss1/GnRH signalling. On the contrary, excess leptin in boys suppresses testosterone production by increasing oestrogen conversion. Low adiponectin in obese girls may contribute to earlier puberty due to a reduced inhibition of Kiss1/GnRH signalling. Low adiponectin in boys is linked to delayed puberty due to its role in maintaining insulin sensitivity and testosterone production. Hyperinsulinemia influences pubertal timing through central and peripheral mechanisms. Insulin acting synergistically with leptin promotes the earlier onset of puberty in girls but not in boys. The effects of exposure to certain EDCs-mostly obesogenic chemicals that mimic the action of natural hormones-on the timing of puberty remain unclear; hence, further research on this topic is needed. Addressing and preventing obesity in children could potentially mitigate these alterations in pubertal timing.

PMID:40564637 | PMC:PMC12190951 | DOI:10.3390/children12060679

Effect of the exposure to brominated flame retardants on hyperuricemia using interpretable machine learning algorithms based on the SHAP methodology - June 26, 2025

PLoS One. 2025 Jun 26;20(6):e0325896. doi: 10.1371/journal.pone.0325896. eCollection 2025.

ABSTRACT

BACKGROUND: Brominated flame retardants (BFRs) are classified as important endocrine disruptors and persistent organic pollutants; nevertheless, there is no comprehensive investigation to evaluate the association between BFRs and hyperuricemia, and the available studies related to this field are exceptionally scarce.

METHODS: For this study, we enrolled 3,812 individuals from NHANES 2005-2016, with nine different types of BFRs serving as the exposure. We conducted advanced machine learning techniques, along with regression analysis to validate our findings from diverse perspectives. Weighted logistic regression were employed to evaluate the association of BFRs for both continuous variables after logarithmic transformation and their quartile subgroups with hyperuricemia. Restricted cubic spline (RCS) analysis was conducted to identify whether a non-linear relationship exists. Subgroup analysis enabled us to explore potential interactions of research findings across different groups. Weighted quantile sum (WQS) regression was performed to assess collective mixture sum impact, along with contributions of each component. Nine machine-learning models were developed for hyperuricemia prediction, and six discrimination characteristics were applied to select the optimal model. SHapley Additive exPlanations (SHAP) was utilized to interpret the contributions of selected variables for model decision-making capacity.

RESULTS: Several BFRs exhibited noticeable positive correlation with the prevalence of hyperuricemia, including PBDE28 (OR: 1.27, 95% CI: 1.05-1.54, P-value = 0.014), PBDE47 (OR: 1.19, 95% CI: 1.02-1.40, P-value = 0.032), PBDE85 (OR: 1.16, 95% CI: 1.01-1.34, P-value = 0.036), PBDE99 (OR: 1.17, 95% CI: 1.02-1.34, P-value = 0.025), and PBDE154 (OR: 1.16, 95% CI: 1.00-1.34, P-value = 0.050) after fully adjustment. The WQS analysis found that the sum effect of BFRs was positively associated with hyperuricemia, of which PBDE28 (28.70%), PBDE85 (22.10%) and PBDE47 (14.90%) were the top 3 components. XGboost exhibited superior performance across several important metrics. The SHAP analysis revealed that the PBDE85, PBDE28 and PBDE154 exhibited considerable influence, ranking after "BMI≥30", "Race-Non-Hispanic Black" and "Hypertension-Yes".

CONCLUSIONS: Combining the outcomes, our study identified PBDE28 and PBDE85 as the two major significant contributors to elevated prevalence of hyperuricemia. Other components, such as PBDE154, PBDE47, PBDE99, and PBDE100, emerged as potential pollutants. These pioneering efforts highlighted the previously underrecognized impact on this environmental and public health concern.

PMID:40570004 | PMC:PMC12200863 | DOI:10.1371/journal.pone.0325896

Multiphase OH Oxidation of Bisphenols: Chemical Transformation and Persistence in the Environment - June 26, 2025

Environ Sci Technol. 2025 Jun 26. doi: 10.1021/acs.est.5c02030. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a common endocrine disruptor widely found in commercial products. Despite negative human health effects, its usage is not fully banned worldwide with ongoing human exposure from sources including dust, aerosol particles, and surfaces. Although attention has been paid to the abundance of alternatives with similar structures that are replacing BPA, uncertainties remain with respect to their chemical transformations and products, toxicity, and environmental fate. We provide the first experimental and modeling assessment of gas-particle multiphase OH oxidation of BPA and six common bisphenol alternatives. We examine the transformation of condensed-phase BPA and its alternatives using an oxidation flow reactor with products monitored by online mass spectrometry. Fourteen products were identified and used to develop a generic mechanism applicable to all bisphenols and to provide inputs into an environmental fate model (PROduction-to-Exposure; PROTEX). Our modeling results highlight the role of heterogeneous surface reactions in determining the indoor retention of these chemicals and their relative environmental persistence indoors and outdoors. All investigated parent molecules yield transformation products predicted to accumulate indoors, with extended indoor persistence if a long chemical lifetime on surfaces (e.g., >100 weeks) is assumed. Evidence of phenoxy radical presence upon oxidation raises a human health risk concern.

PMID:40569786 | DOI:10.1021/acs.est.5c02030

Inflammaging and metabolic syndrome: molecular mechanisms. - June 26, 2025

Adv Gerontol. 2025;38(1):118-125.

ABSTRACT

One of the most pressing medical and social problems in the world is the widespread prevalence of chronic age-associated pathology, which includes metabolic syndrome. Metabolic inflammation accompanying metabolic diseases and aging have a common pathogenesis, the basis of which is the activation of the innate immune system and an increase in the inflammatory background. During the aging process, chronic, asymptomatic, sluggish inflammation develops, called inflamaging, which leads to a cascade of pathological changes that disrupt the functions of adipose tissue and the endocrine system, and thereby contributes to the development of a number of diseases. Inflamaging is supported by various stimuli, including pathogens, endogenous cellular debris and defective molecules, as well as excess nutrients. The review examines the common mechanisms of inflammation, aging and metabolic homeostasis disorders, emphasizing the significant role of inflammaging in the development of metabolic syndrome, as well as biomarkers of age-associated diseases, the use of which as targets for therapeutic treatment can help in the fight against metabolic syndrome.

PMID:40570223

Polystyrene nanoplastics act as endocrine disruptors altering neurotransmitter levels and locomotor activity via estrogen receptor during early zebrafish development - June 26, 2025

Aquat Toxicol. 2025 Jun 22;286:107468. doi: 10.1016/j.aquatox.2025.107468. Online ahead of print.

ABSTRACT

Polystyrene nanoplastics (PSNPs) are emerging endocrine disruptors with significant neurotoxic potential. This study evaluates the impact of PSNP exposure on neurotransmitter levels, locomotor activity, and gene expression in zebrafish (Danio rerio) embryos and larvae, with a focus on estrogen receptor (ER) signaling pathways using the antagonist ICI 182,720 (ICI). Zebrafish embryos were exposed to varying PSNP concentrations (0.01, 0.1, 1, and 10 µg/mL) with or without 10 µM ICI co-incubation from 2 to 120 hpf. PSNP exposure significantly reduced TH-positive neuron area, increased apoptosis in the brain, impaired locomotor activity, and increased anxiety-like behavior. These effects were associated with downregulated dopaminergic gene expression (th1, th2, dat, ddc), upregulated apoptotic markers (tp53, casp3, casp9, bax), and decreased anti-apoptotic bcl2a expression. Additionally, PSNPs significantly reduced acetylcholinesterase (AChE) activity. Interestingly, co-incubation with ICI reversed neurotransmitter levels, reducing brain apoptosis, normalized locomotor responses, gene expression changes, and brought AChE activity back to control levels, indicating that the neurotoxic effects of PSNPs are mediated through ER pathways. This study provides evidence that PSNPs act as endocrine disruptors, interfering with neurotransmitter signaling, promoting brain apoptosis, and altering behavior via ER pathways during early zebrafish development.

PMID:40570603 | DOI:10.1016/j.aquatox.2025.107468

A comparative study on degradation kinetics and toxicity changes of BPA and BPS in UV-based advanced oxidation processes - June 26, 2025

Environ Res. 2025 Jun 24;284:122223. doi: 10.1016/j.envres.2025.122223. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) and Bisphenol S (BPS) are endocrine-disrupting chemicals that pose significant ecological and health risks due to their persistence and toxicity. This study presents a comprehensive comparison of three UV-based advanced oxidation processes (UV-AOPs: UV/Cl, UV/PDS, and UV/H₂O₂) for degrading BPA and BPS, with an emphasis on correlating degradation efficiency to the toxicity of transformation products (TPs). Using a 500 W mercury vapor lamp, we demonstrate how differences in electronic properties (e.g., BPA's electron-rich rings vs. BPS's electron-withdrawing sulfonyl group) influence radical selectivity (SO₄^•-, •OH, RCS) and by-product risks. The effects of oxidant dosage, pH, and dissolved organic matter were examined. The toxicity of degradation by-products was evaluated using an integrated approach combining ECOSAR predictions and Vibrio fischeri bioassays to reveal critical trade-offs between degradation rates and TP safety. The UV/PDS system demonstrated the highest BPA removal efficiency (96.5 % in 10 min, k = 0.3185 ± 0.034 min^-1) under alkaline conditions, primarily via sulfate radicals (SO₄^•-). In contrast, BPS degradation was less efficient (k = 0.0910 min^-1) due to the lower reactivity of its sulfonyl group. The UV/Cl process generated chlorinated by-products, such as TP07, with toxicity levels 1.5 to 2.0 times higher than the parent compounds, while UV/H₂O₂ produced hydroxylated by-products that were 25 % more toxic than BPA. Notably, chlorinated derivatives increased toxicity in BPA but reduced it in BPS due to steric hindrance from the sulfonyl group, a structural nuance not previously reported in AOP studies. Oxidized by-products were generally less toxic, whereas fragmented products exhibited higher toxicity than their precursors. These findings support pollutant-specific optimization of UV-AOPs, identifying UV/PDS as the most effective for BPA degradation while emphasizing the need for sulfonyl-targeted refinement in BPS treatment.

PMID:40571074 | DOI:10.1016/j.envres.2025.122223

Multi-Omics Analysis of Chronic Heat Stress-Induced Biological Effects, Liver Injury, and Heat Tolerance Mechanisms via Oxidative and Anti-Inflammatory Pathways in Early-Pregnancy Sows - June 26, 2025

Antioxidants (Basel). 2025 May 23;14(6):623. doi: 10.3390/antiox14060623.

ABSTRACT

The prenatal environment critically influences sow and offspring health, with the liver being highly susceptible to heat stress (HS) and vital for antioxidant defense. However, mechanisms underlying HS impacts on early pregnancy and hepatic adaptation remain unclear. This study applied multi-omics to analyze chronic HS responses in early-pregnancy sows. Results demonstrated that HS reduced blood oxygen (PO₂) and basophils while elevating red blood cell parameters (RBC, HGB, and HCT). Endocrine disruptions included upregulated adrenal hormones (ACTH and cortisol) and suppressed thyroid (T3 and TSH) and reproductive hormones (LH1 and FSH). Liver dysfunction was evident through elevated biomarkers (AST, ALT, and TBIL) and pro-inflammatory IL-6, coupled with reduced anti-inflammatory IL-10. HS induced oxidative stress, marked by increased total antioxidant capacity (T-AOC) but decreased SOD and MDA levels. Liver tissue exhibited apoptosis (Bax/CD8 upregulated and Bcl-2 downregulated) and upregulated heat shock proteins (HSP70/90). Multi-omics analysis demonstrated that under heat stress conditions, the pyrimidine metabolism, oxidative phosphorylation, and tryptophan metabolism pathways were significantly upregulated in the liver. This upregulation may be mediated by key metabolites, including AMP, NAD, and UMP. These metabolites likely contribute to the body's adaptation to heat stress. Chronic HS impaired liver function and anti-inflammatory responses but triggered compensatory antioxidant and metabolic reprogramming. These findings underscore the liver's dual characteristics of vulnerability and resilience under high-temperature stress, offering valuable mechanistic insights that can inform strategies to enhance heat tolerance in pregnant sows.

PMID:40563258 | PMC:PMC12189682 | DOI:10.3390/antiox14060623

Effect of Maternal Hyperglycemia on Fetal Pancreatic Islet Development - June 26, 2025

Biology (Basel). 2025 Jun 19;14(6):728. doi: 10.3390/biology14060728.

ABSTRACT

Hyperglycemia during fetal development disturbs extracellular matrix (ECM) synthesis and deposition patterns, which disrupts organogenesis and adult organ function. Although the ECM cooperates in pancreas development, little is known about the effects of hyperglycemia on the pancreatic ECM during development. This study investigates the effect of severe maternal hyperglycemia on ECM composition and endocrine pancreas development in E19.0 mouse fetuses. Deposition patterns of pan-laminin, laminin (alpha 1 and gamma 1 chains) and integrin alpha 3 were evaluated by immunostaining. The proliferative index of islet cells and alpha and beta cell distribution were evaluated by PCNA, glucagon and insulin immunostaining, respectively. Pdx1 and Pax4 expressions were analyzed by RT-qPCR. While for pan-laminin and laminin (alpha1 and gamma1 chains) deposition was weaker in the endocrine pancreas of hyperglycemic mothers' fetuses, integrin alpha 3 deposition in the basement membrane was increased. The proliferative index of endocrine cells was lower in the hyperglycemic group, while the beta-cell area was increased. In addition, there was a tendency towards lower Pdx1 and increased Pdx4 expression. These data suggest that maternal hyperglycemia alters fetal endocrine pancreas morphogenesis by modifying peri-islet basement membrane molecule patterns, promoting a decrease in endocrine cell proliferation associated with changes in the expression of important growth factors for the beta cells differentiated and the proliferative state.

PMID:40563978 | PMC:PMC12189325 | DOI:10.3390/biology14060728

Beyond Bone Loss: A Biology Perspective on Osteoporosis Pathogenesis, Multi-Omics Approaches, and Interconnected Mechanisms - June 26, 2025

Biomedicines. 2025 Jun 12;13(6):1443. doi: 10.3390/biomedicines13061443.

ABSTRACT

Osteoporosis is a systemic bone disorder characterized by decreased bone mass and deteriorated microarchitecture, leading to an increased risk of fractures. Recent studies have revealed that its pathogenesis involves complex biological processes beyond bone remodeling, including oxidative stress, chronic inflammation, cellular senescence, osteoimmunology, gut microbiota alterations, and epigenetic modifications. Oxidative stress disrupts bone homeostasis by promoting excessive free radical production and osteoclast activity. Chronic inflammation and the accumulation of senescent cells impair skeletal repair mechanisms. Advances in osteoimmunology have highlighted the critical role of immune-bone crosstalk in regulating bone resorption and formation. Moreover, the gut-bone axis, mediated by microbial metabolites, influences bone metabolism through immune and endocrine pathways. Epigenetic changes, such as DNA methylation and histone modification, contribute to gene-environment interactions, affecting disease progression. Multi-omics approaches (genomics, proteomics, and metabolomics) systematically identify molecular networks and comorbid links with diabetes/cardiovascular diseases, revealing pathological feedback loops that exacerbate bone loss. In conclusion, osteoporosis pathogenesis extends beyond bone remodeling to encompass systemic inflammation, immunometabolic dysregulation, and gut microbiota-host interactions. Future research should focus on integrating multi-omics biomarkers with targeted therapies to advance precision medicine strategies for osteoporosis prevention and treatment.

PMID:40564162 | PMC:PMC12190919 | DOI:10.3390/biomedicines13061443

Percutaneous absorption of climbazole: In vitro data from human skin - June 26, 2025

Regul Toxicol Pharmacol. 2025 Jun 24;162:105895. doi: 10.1016/j.yrtph.2025.105895. Online ahead of print.

ABSTRACT

Climbazole is an antifungal substance used as an active ingredient or antimicrobial preservative in pharmaceuticals and personal care products. It is classified by the EU as an acute toxicant (Category 4), and ECHA has recently confirmed its endocrine disruptor concern. Data on climbazole's skin permeability, and consequently its occupational risks, are limited. The aim of this study was to generate percutaneous absorption data in line with OECD guidelines to support occupational exposure assessment. In vitro experiments using 4.1 μg/cm² [¹⁴C]-labelled climbazole were conducted on freshly excised human skin samples placed in Franz diffusion cells, monitoring absorption over 20 h. The absorption profile data were used to calculate key parameters, including steady-state flux, lag time, and skin permeability coefficient (K_p). The dose distribution across various compartments, including the skin, was evaluated. The individual skin layers were isolated by sequential tape-stripping, followed by epidermis-dermis separation to more precisely measure radioactivity levels. This information was used to predict the potential for further absorption of the dose retained within the skin. The presence of climbazole metabolites in the receptor fluid was also investigated. The K_p was determined to be 4.7 x 10^-3 cm/h. Significant dermal absorption was measured, highlighting potential occupational risks. Climbazole is mainly absorbed with biotransformation: 67 % of the absorbed dose was detected as metabolites. These new percutaneous absorption data will enhance the assessment of the occupational risks associated with dermal exposure to climbazole.

PMID:40571243 | DOI:10.1016/j.yrtph.2025.105895

Comparative Analysis of Letrozole and Estradiol Valerate PCOS Models: Reproductive and Metabolic Outcomes with and Without High-Fat Diet - June 26, 2025

Biology (Basel). 2025 May 23;14(6):592. doi: 10.3390/biology14060592.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligoanovulation, and polycystic ovarian morphology. Despite its classification as a reproductive disorder, PCOS is closely associated with metabolic dysregulation, including insulin resistance and obesity. An ideal animal model for PCOS should replicate both reproductive and metabolic features of the condition. In this study, we compared two widely used postnatal PCOS models (letrozole and estradiol valerate [EV]) administered alone or in combination with a high-fat diet (HFD), assessing their ability to induce both the reproductive and metabolic features. Letrozole treatment led to significant weight gain and increased visceral adiposity, effects that were amplified by HFD. Conversely, EV treatment showed a tendency toward reduced body mass. While neither model significantly altered fasting glucose levels, letrozole combined with HFD impaired glucose tolerance, supporting its role in metabolic dysfunction. Hyperandrogenism was more consistently induced by letrozole compared to EV, aligning with clinical PCOS phenotypes. Both treatments disrupted estrous cyclicity and induced polycystic ovarian morphology, though metabolic disturbances were more pronounced in the letrozole model. These findings suggest that letrozole, particularly in combination with HFD, provides a more consistent model for studying both the reproductive and metabolic facets of PCOS.

PMID:40563843 | PMC:PMC12189083 | DOI:10.3390/biology14060592

Isatin ameliorates ovarian inflammation and apoptosis caused by hormonal imbalances in PCOS mice - June 26, 2025

Biochem Pharmacol. 2025 Jun 24;239:117083. doi: 10.1016/j.bcp.2025.117083. Online ahead of print.

ABSTRACT

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in women of childbearing age. Isatin (ISA) is a bioactive compound naturally found in mammalian body fluids and tissues, known for its potent antioxidant, anti-inflammatory, and anticancer properties. We used letrozole to induce a PCOS mouse model and evaluated the reproductive benefits of ISA. The mice were initially grouped according to the concentration of ISA administered at 25, 50, and 100 mg/kg. Subsequently, research results indicated that the optimal concentration was determined to be 100 mg/kg, while a positive control group was established using 150 mg/kg of metformin. The results demonstrated that PCOS mice exhibited obesity, disrupted estrous cycles, polycystic ovaries, insulin resistance, disruption of cytoskeletal structure, mitochondrial damage and decreased fertility. Additionally, the elevated androgen levels in PCOS mice also led to ovarian inflammation, oxidative stress, and apoptosis. However, ISA effectively reversed these damages. High-throughput sequencing revealed that ISA significantly downregulated the expression of genes related to androgen production, including STAR, CYP11A1 and CYP17A1. ISA can also reduce the expression of pro-inflammatory factors and inhibit the activation of the NF-κB pathway, thereby alleviating ovarian inflammation. Post-treatment with ISA resulted in reduced levels of ROS and MDA, and inhibited apoptosis in the ovarian tissue of PCOS mice by modulating apoptosis related proteins, such as BAX, P53, BCL-2, and Caspase-3. In summary, a protective effect of ISA on the ovaries in the letrozole-induced PCOS mouse model was demonstrated by regulating hormone secretion, alleviating inflammation and oxidative stress, and subsequently inhibiting ovarian cell apoptosis.

PMID:40571218 | DOI:10.1016/j.bcp.2025.117083

The pyrethroid insecticide deltamethrin disrupts neuropeptide and monoamine signaling pathways in the gastrointestinal tract - June 26, 2025

Abstract

Enteroendocrine cells (EECs) are a rare cell type of the intestinal epithelium. Various subtypes of EECs produce distinct repertoires of monoamines and neuropeptides which modulate intestinal motility and other physiologies. EECs also possess neuron-like properties, suggesting a potential vulnerability to ingested environmental neurotoxicants. One such group of toxicants are pyrethroids, a class of prevalent insecticides used residentially and agriculturally. Pyrethroids agonize voltage-gated sodium channels (VGSCs), inducing neuronal excitotoxicity, and affect the function of monoamine-producing neurons. Given their anatomical location at the interface with the environment and their expression of VGSCs, EECs likely represent a vulnerable cell-type to oral pyrethroid exposure. In this study, we used the EEC cell line, STC-1 cells, to evaluate the effects of the common pyrethroid deltamethrin on the functional status of EECs. We find that deltamethrin impacts both expression of serotonergic pathways and inhibits the adrenergic-evoked release of an EEC hormone, GLP-1, in vitro. In a mouse model of oral exposure, we found that deltamethrin induced an acute, yet transient, loss of intestinal motility, in both fed and fasted conditions. This constipation phenotype was accompanied by a significant decrease in peripheral serotonin production and an inhibition of nutrient-evoked intestinal hormone release. Together, these data demonstrate that deltamethrin alters monoaminergic signaling pathways in EECs and regulates intestinal motility. This work demonstrates a mechanistic link between pyrethroid exposure and intestinal impacts relevant to pyrethroid-associated diseases, including inflammatory bowel disease, neurodegenerative disease, and metabolic disorders.

Tributyltin Alters Seric Bile Acid Pool Composition in Male Rats - June 25, 2025

Toxics. 2025 May 26;13(6):440. doi: 10.3390/toxics13060440.

ABSTRACT

Tributyltin (TBT), a recognized endocrine disruptor, is associated with metabolic diseases, including obesity, type 2 diabetes, non-alcoholic steatohepatitis, and osteoporosis. Bile acids (BAs) play pivotal roles in lipid digestion and absorption. However, there are no studies to illustrate the effects of TBT on BA pool composition in circulation. Here, rats were treated with TBT (50 μg/kg) or a vehicle control once every three days for sixty days to analyze serum BA levels using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The liver tissue sections and lipid levels of rats were examined using conventional methods. TBT induced sporadic cholestasis in the livers of rats and significantly reduced the levels of five BAs, including four conjugated BAs [acidtaurocholic acid (TCA), taurodeoxycholic acid (TDCA), taurochenodeoxycholic acid (TCDCA), and tauro-β-muricholic acid (Tβ-MCA)] and one unconjugated bile acid [dehydrolithocholic acid (DLCA)], while the serum levels of triglyceride, cholesterol, and bilirubin were unaltered by TBT treatment. These results indicate that TBT exposure affected the BA pool composition in circulation, especially the taurine-conjugated BAs.

PMID:40559913 | PMC:PMC12196776 | DOI:10.3390/toxics13060440

Chronic Low-Dose Phoxim Exposure Impairs Silk Production in Bombyx mori L. (Lepidoptera: Bombycidae) by Disrupting Juvenile Hormone Signaling-Mediated Fibroin Synthesis - June 25, 2025

Toxics. 2025 May 23;13(6):427. doi: 10.3390/toxics13060427.

ABSTRACT

Phoxim is a pesticide extensively applied in mulberry fields, and residues may persist on leaves even after the recommended pre-harvest interval. However, the potential risks of these residues to Bombyx mori L. (Lepidoptera: Bombycidae) have long been overlooked. The results demonstrated that chronic low-dose exposure from the second to fifth instars significantly impaired silkworm development and silk production. Specifically, larvae in the 0.316 μg/mL treatment group (1/2 LC₅₀) exhibited a significant reduction in body weight, while the cocoon shell ratio was significantly decreased in both the 0.079 μg/mL (1/8 LC₅₀) and 1/2 LC₅₀ groups. Cocoon deformities were observed in the 0.032 μg/mL (1/20 LC₅₀), 1/8 LC₅₀, and 1/2 LC₅₀ groups. Histopathological analysis revealed silk gland damage in the treatment groups, with severity increasing with higher phoxim concentrations. Biochemical analyses indicated elevated malondialdehyde (MDA) levels accompanied by increased superoxide dismutase (SOD) and peroxidase (POD) activities. Notably, phoxim exposure selectively reduced juvenile hormone (JH) titers without affecting ecdysone titers. JH-regulated genes including the receptors Met1 and Met2, and transcription factors Kr-h1 and Dimm were downregulated, accompanied by suppressed expression of the fibroin synthesis gene Fib-H. These results collectively indicate that chronic low-concentration phoxim exposure disrupts endocrine regulation, damages silk gland integrity, and ultimately reduces silk production in silkworm.

PMID:40559901 | PMC:PMC12196826 | DOI:10.3390/toxics13060427

Exploring the Role of Bifenthrin in Recurrent Implantation Failure and Pregnancy Loss Through Network Toxicology and Molecular Docking - June 25, 2025

Toxics. 2025 May 29;13(6):454. doi: 10.3390/toxics13060454.

ABSTRACT

Bifenthrin (BF) is a widely used pyrethroid pesticide recognized as an endocrine-disrupting chemical (EDC). Previous studies have confirmed that chronic exposure to BF is associated with various health risks. However, its potential association with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) remains unclear. In this study, the potential targets of BF were identified using several databases, including the Comparative Toxicogenomics Database (CTD), TargetNet, GeneCards, SwissTargetPrediction, and STITCH. Differentially expressed genes (DEGs) associated with RIF were obtained from bulk RNA-seq datasets in the GEO database. Candidate targets were identified by intersecting the predicted BF-related targets with the RIF-associated DEGs, followed by functional enrichment analysis using the DAVID and g:Profiler platforms. Subsequently, hub genes were identified based on the STRING database and Cytoscape. A diagnostic model was then constructed based on these hub genes in the RIF cohort and validated in an independent recurrent pregnancy loss (RPL) cohort. Additionally, we performed single-cell type distribution analysis and immune infiltration profiling based on single-cell RNA-seq and bulk RNA-seq data, respectively. Molecular docking analysis using AutoDock Vina was conducted to evaluate the binding affinity between BF and the four hub proteins, as well as several hormone-related receptors. Functional enrichment results indicated that the candidate genes were mainly involved in apoptotic and oxidative stress-related pathways. Ultimately, four hub genes-BCL2, HMOX1, CYCS, and PTGS2-were identified. The diagnostic model based on these genes exhibited good predictive performance in the RIF cohort and was successfully validated in the RPL cohort. Single-cell transcriptomic analysis revealed a significant increase in the proportion of myeloid cells in RPL patients, while immune infiltration analysis showed a consistent downregulation of M2 macrophages in both RIF and RPL. Moreover, molecular docking analysis revealed that BF exhibited high binding affinity to all four hub proteins and demonstrated strong binding potential with multiple hormone receptors, particularly pregnane X receptor (PXR), estrogen receptor α (ESRα), and thyroid hormone receptors (TR). In conclusion, the association of BF with four hub genes and multiple hormone receptors suggests a potential link to immune and endocrine dysregulation observed in RIF and RPL. However, in vivo and in vitro experimental evidence is currently lacking, and further studies are needed to elucidate the mechanisms by which BF may contribute to RIF and RPL.

PMID:40559927 | PMC:PMC12196838 | DOI:10.3390/toxics13060454

Role of NR1D1 in Bisphenol A-Induced Anxiety-like Behavior and Inflammation in Zebrafish Larvae - June 25, 2025

Toxics. 2025 May 28;13(6):449. doi: 10.3390/toxics13060449.

ABSTRACT

Bisphenol A (BPA) is a widespread environmental endocrine disruptor with significant neurodevelopmental and behavioral risks. The present study explored the role of the circadian clock protein NR1D1 in mediating BPA-induced anxiety-like behavior and brain inflammation early in life. Zebrafish embryos exposed to BPA exhibited anxiety-like behavior characterized by altered motor activity patterns. Notably, BPA exposure suppressed the expression of the circadian clock gene nr1d1, accompanied by increased transcriptional and protein levels of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α. These changes created a pro-inflammatory microenvironment that disrupted dopamine system homeostasis, contributing to the observed behavioral abnormalities. Activation of NR1D1 using GSK effectively reversed BPA-induced inflammatory responses and restored normal dopamine levels and behavioral phenotypes. These findings highlight NR1D1 as a critical regulator linking circadian rhythm disruption, neuroinflammation, and dopaminergic dysfunction to anxiety-like behavior. This study provides novel insights into the mechanisms underlying BPA-induced neurotoxicity and identifies NR1D1 as a potential therapeutic target for mitigating the adverse effects of early-life BPA exposure.

PMID:40559921 | PMC:PMC12197085 | DOI:10.3390/toxics13060449

Association of Per- and Polyfluoroalkyl Substances with Pan-Cancers Associated with Sex Hormones - June 25, 2025

Toxics. 2025 Jun 14;13(6):501. doi: 10.3390/toxics13060501.

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous environmental contaminants with potential endocrine-disrupting properties. This study examines the association between exposure to multiple PFASs and pan-cancers associated with sex hormones (PCSH) while accounting for potential non-linear relationships and interactions. We analyzed data from the National Health and Nutrition Examination Survey (NHANES), spanning two-year cycles from 1999 to 2012 and including 14,373 participants. Serum concentrations of six PFAS-perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorodecanoic acid (PFDE), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA)-were assessed for their relationship with PCSH. The statistical analyses included descriptive statistics, Spearman and Pearson correlation analyses, and both linear and logistic regression models. Additionally, Bayesian kernel machine regression (BKMR) was applied to capture potential nonlinear relationships and interactions. The initial t-tests showed a statistically significant difference in PFOS levels between individuals with and without PCSH (p = 0.0022), with higher mean PFOS levels in the PCSH group. Chi-square tests revealed a significant association between ethnicity and PCSH (p < 0.001). Linear and logistic regression analyses revealed significant associations for PFOS. BKMR analysis identified PFOA as having the highest posterior inclusion probability, indicating its importance in explaining PCSH risk. Univariate exposure-response analysis revealed limited individual PFAS effects. However, bivariate analysis indicated a complex U-shaped interaction pattern among many joint PFAS assessments. The overall exposure effect analysis suggested that the combined impact of all PFASs was more strongly associated with PCSH at exposure levels below the 0.5 quantile compared to higher levels. Single-variable interaction analyses highlighted PFOA and PFOS as the most interactive PFASs when evaluating their interaction with combined exposure to all other PFASs. In summary, while the initial findings suggested a positive association between PFOS and PCSH, the BKMR analysis revealed complex non-linear relationships and interactions among PFAS. These findings highlight the importance of evaluating PFASs as a mixture rather than as individual chemicals and using techniques that can capture non-linear relationships and interactions.

PMID:40559974 | PMC:PMC12197098 | DOI:10.3390/toxics13060501

Health Hazards Associated with Exposure to Endosulfan: A Mini-Review - June 25, 2025

Toxics. 2025 May 29;13(6):455. doi: 10.3390/toxics13060455.

ABSTRACT

Endosulfan, a persistent organochlorine pesticide, has raised global concern due to its toxicological effects on human health and the environment. The popularity of endosulfan was driven by its effectiveness and low cost compared to alternative insecticides. The compound's environmental persistence and bioaccumulative properties also contributed to its sustained use over several decades. Despite regulatory bans in many countries, residues of endosulfan continue to be detected in soil, water, and food sources, posing a threat through chronic exposure. Although endosulfan has been listed in the Stockholm Convention as a persistent organic pollutant targeted for global elimination, it is still used illegally in some countries. This mini-review synthesizes current knowledge on its toxicological profile, including neurotoxicity, endocrine disruption, reproductive toxicity, potential carcinogenicity, and acute poisoning, based on the latest scientific literature. The paper also highlights current regulatory frameworks, historical usage trends, global distribution and alternatives to endosulfan in agriculture. Understanding the scope of its health impacts and ongoing risks is crucial for policymakers, researchers, and public health authorities seeking to protect populations from legacy pollutants. In addition, recognizing the long-term impacts of endosulfan is essential for effective health risk assessment, environmental monitoring, and the promotion of safer alternatives.

PMID:40559928 | PMC:PMC12196845 | DOI:10.3390/toxics13060455

Endocrine disrupting chemicals exposure and health: An umbrella review - June 25, 2025

Ecotoxicol Environ Saf. 2025 Jun 24;302:118574. doi: 10.1016/j.ecoenv.2025.118574. Online ahead of print.

ABSTRACT

The aim of this umbrella review was to evaluate the quality, potential biases, and validity of the existing evidence on the relationship between endocrine disrupting chemicals (EDCs) exposure and health outcomes, through a comprehensive review of available meta-analyses. The included meta-analyses were searched across multiple databases, including PubMed, Embase, and Web of Science. This umbrella review included systematic reviews and meta-analyses of randomized controlled trials, cohort studies, case-control studies, and cross-sectional studies that assessed the impact of EDCs exposure on various health outcomes in humans. The search resulted in the identification of 67 meta-analyses and 109 health outcomes from 7552 unique articles. All of these 109 health outcomes were derived from meta-analyses of observational studies. EDCs exposure included pesticides (n = 30), BPA (n = 13), PAHs (n = 18), PFAS (n = 10), and heavy metals (n = 38). Sixty-nine harmful associations were found to be statistically significant, along with one beneficial association. The remaining 39 outcomes were either harmful or beneficial but did not reach statistical significance. Significant harmful associations between EDCs exposure and 22 cancer outcomes, 21 neonatal/infant/child-related outcomes, 18 metabolic disorder outcomes, 17 cardiovascular disease outcomes, 11 pregnancy-related outcomes, and 20 other outcomes (renal, neuropsychiatric, respiratory, and hematologic) were detected. Exposure to environmental EDCs is closely linked to a wide range of adverse health outcomes. Given the widespread exposure to these pollutants globally, precautionary policies may be warranted to reduce population-level exposure and mitigate potential health risks associated with environmental chemicals.

PMID:40561611 | DOI:10.1016/j.ecoenv.2025.118574

Endocrine disrupting chemicals exposure and health: An umbrella review - June 25, 2025

Ecotoxicol Environ Saf. 2025 Jun 24;302:118574. doi: 10.1016/j.ecoenv.2025.118574. Online ahead of print.

ABSTRACT

PMID:40561611 | DOI:10.1016/j.ecoenv.2025.118574

Multiple nuclear receptor-regulated endocrine disrupting effects: A case study for bisphenol-induced crosstalk between RARalpha and ERalpha signaling pathways - June 25, 2025

J Hazard Mater. 2025 Jun 20;495:139005. doi: 10.1016/j.jhazmat.2025.139005. Online ahead of print.

ABSTRACT

Given the intricate regulation of endocrine homeostasis, the crosstalk among multiple nuclear receptors (NRs) induced by emerging chemicals has garnered increasing attention. Of particular, the interaction between estrogen receptor alpha (ERα) and retinoic acid receptor alpha (RARα) is now a new focus of research. Herein, six representative analogs of bisphenol A (i.e., BPAF, BPB, BPE, BPF, BPS, and BPZ) were screened for their estrogenic and retinoid-like activities by using the combination of in vitro and in silico assays. Two bisphenols with relatively high ERα and RARα binding affinities (i.e., BPB and BPAF) were selected to study the crosstalk between these two NR-regulated signaling in human breast carcinoma (MCF-7) cells. Both agonism and antagonism of RARα inhibited bisphenol-activated ER-dependent cell proliferation and the downstream gene transcription. Differently, bisphenol-mediated RARα signaling was inhibited by ERα agonism, but enhanced by ERα antagonism. The present study, for the first time, uncovered the inhibition effect of bisphenols on RARα signaling via ERα agonism, and highlighted the antagonistic crosstalk between ERα and RARα signaling. The findings provide a novel perspective to understand the complicated endocrine disrupting effects of emerging chemicals with binding affinities for multiple NRs, and emphasize the importance of studying the crosstalk between diverse NR-regulated signaling that is concerned.

PMID:40561951 | DOI:10.1016/j.jhazmat.2025.139005

The intracellular free concentration of endocrine disrupting chemicals enables translation between cell-free and cell-based estrogenic activity assays - June 25, 2025

Environ Toxicol Pharmacol. 2025 Jun 23;117:104750. doi: 10.1016/j.etap.2025.104750. Online ahead of print.

ABSTRACT

Many environmental toxicants can activate estrogen receptor α (ERα), disrupting normal endocrine function. While these activities are predicted across in silico, in vitro, and in vivo models, translating active concentrations between these systems remains challenging. We hypothesized that cellular uptake and the resulting free intracellular toxicant concentration could bridge this gap. Using cell-free (hER) and cell-based (ERα-CALUX cells) estrogen assays, we tested this hypothesis by determination of the free intracellular concentration available for binding to the intracellularly located ERα. Predictive modeling identified three classes of estrogenic chemicals from the ToxCast collection: bisphenols, parabens, and phthalates. Experimental data confirmed potency differences of up to 100-fold between the cell-free and cell-based models. Cellular toxicokinetic (TK) parameters, including cellular uptake and intracellular binding, were determined using computational and experimental methods. Incorporating experimental TK parameters significantly improved the correlation between ERα activities in the cell-free and cellular models (from r = 0.6230, P = 0.0989 without corrections to r = 0.8869, P = 0.0033 after corrections), and bridged the gap between the cell free and cell based assays. Both computational and experimental TK parameters varied widely across chemical classes and compounds. Correcting active concentrations for free intracellular levels enhanced assay correlations, with experimentally derived corrections showing the strongest improvement with r = 0.8869 (compared to the in silico derived corrections with r = 0.811). Our findings highlight the critical role of free intracellular concentration in determining the biological activity of estrogenic toxicants and emphasize its importance in accurately assessing their endocrine-disrupting potential.

PMID:40562181 | DOI:10.1016/j.etap.2025.104750

Therapeutic Potential of Aloe vera and Aloe vera Fabricated Silver Nanoparticles on Reproductive Function in Male Mice Exposed to Hexavalent Chromium - June 25, 2025

Cell Biochem Biophys. 2025 Jun 26. doi: 10.1007/s12013-025-01806-2. Online ahead of print.

ABSTRACT

Hexavalent chromium Cr (VI), an endocrine disruptor, has been a possible risk factor for male-oriented infertility, due to its damaging effect on testes. Thus, we sought to analyze the protective effect of Aloe vera (A. vera) and their mediated silver nanoparticles on testes in mice. Sixty male mice were exposed to Cr (VI) and A. vera extract (AV) and their mediated silver nanoparticles (AV+NP) as protective agents for 60 days. The organ index, hormone analysis, enzyme analysis, metal estimation, computer assisted sperm analysis (CASA), histopathology of testes and micrometric data were assessed using one-way ANOVA. A significant reduction was found in the level of catalase (87.1 ± 7.02 mmol/mL), superoxide dismutase (61.8 ± 2.5 mmol/mL), glutathione (1.51 ± 0.9 µmol/mL), luteinizing hormone (LH) (1.6 ± 0.3 ng/mL), and testosterone (2.3 ± 0.2 ng/mL) in Cr exposed group. However, a significant increase was found in Cr exposed mice in follicle-stimulating hormone (FSH) (159.9 ± 4.98 ng/mL) level. With administration of AV and AV+NP, we found a significant increase in level of catalase (143.4 ± 2.6 mmol/mL; 134.8 ± 9.1 mmol/mL), superoxide dismutase (205.8 ± 13.0 mmol/mL; 187.3 ± 9.9 mmol/mL), glutathione (2.98 ± 0.2 µmol/mL; 3.06 ± 0.2 µmol/mL), luteinizing hormone (LH) (2.9 ± 0.2 ng/mL; 3.1 ± 0.2 ng/mL), and testosterone (3.9 ± 0.1 ng/mL; 4.58 ± 0.2 ng/mL) respectively, whereas, FSH level was decreased (84.7 ± 7.2 ng/mL; 70.4 ± 4 ng/mL). The CASA showed a noticeable decrease in sperm quantity and kinematics after Cr exposure. In AV and AV+NP exposed groups, the sperm kinematics were improved significantly. The histopathological studies showed necrosis of Leydig cells, absence of sperm tails, and destruction in the zone of mitosis and meiosis in Cr-exposed groups. The micro morphometric analysis showed a significant reduction in the size of spermatogonia (38.9 ± 0.7 µm), size of spermatocytes (26.91 ± 1.4 µm), head breadth (5.4 ± 0.7 µm), head length (19.98 ± 1.2 µm), middle piece, and tail length (0.00 ± 0.0 µm; 0.00 ± 0.0 µm) in Cr exposed mice. However, with the AV and AV+NP administration, the testis architecture was improved, exhibiting an improved zone of mitosis and meiosis. A. vera exposure induced a significant decrease in the size of spermatogonia (24.1 ± 2.4 µm), and size of spermatocytes (18.7 ± 1.2 µm), whereas a significant increase in sperm head breadth (15.1 ± 0.8 µm), and head length (34.4 ± 2.8 µm) was found. We found that AV and AV+NP can potentially reduce oxidative damage induced by Cr (VI) in testes and promote fertility.

PMID:40563078 | DOI:10.1007/s12013-025-01806-2