Search Results (246)

Epigenetic regulation is pivotal in reproductive processes, such as oocyte maturation and pre-implantation embryonic development, and it impacts gene expression without altering DNA sequence through mechanisms including DNA methylation, histone modifications, and non-coding RNAs. Primarily, microRNA-21 is involved in meiotic progression, apoptosis, and cumulus cell function, which are necessary for oocyte competency. miR-21 dysregulation can lead to improper oocyte maturation and poor embryonic development, ultimately causing developmental defects. During pre-implantation embryonic development, DNA methylation and histone modifications contribute to cellular reprogramming, ensuring proper gene activation and repression. Environmentally, endocrine disruptors affect miR-21 expression, potentially disrupting pathways involved in reproductive health and developmental programming. Overall, this review explores the correlation between epigenetics, miRNA regulation, and environmental factors, emphasizing the intricacies of oocyte maturation and pre-implantation embryonic development. This highlights the need for additional mechanistic and translational research in reproductive epigenetics. Full article

Ischemic heart disease (IHD) is a chronic and progressive condition characterized by reduced blood flow, mainly due to atherosclerosis. It is currently the leading cause of mortality among cardiovascular diseases. In recent years, per- and polyfluoroalkyl substances (PFAS), a group of ubiquitous and highly persistent environmental contaminants, have emerged as potential risk factors for IHD. PFAS are well-established endocrine disruptors and have been associated with hypercholesterolemia, hypertriglyceridemia, and insulin resistance. Despite the limited number of epidemiological studies and inconsistent findings from occupational settings, accumulating evidence suggests that elevated exposure to certain PFAS compounds may increase the risk of IHD and vascular dysfunction, including processes related to atherosclerosis development, sometimes with dose–response relationships and sex-specific patterns. Mechanistic evidence supports this link, indicating that PFAS exposure induces molecular and cellular alterations relevant to cardiovascular pathophysiology, including increased oxidative stress and vascular inflammation, and disruption of lipid metabolism. In addition, PFAS may affect epigenetic regulation, telomere length, and mitochondrial DNA copy number, which are emerging biomarkers associated with atherosclerosis and IHD and may indicate early cardiovascular vulnerability. Future research integrating innovative approaches and advanced analytical techniques may help address current knowledge gaps and clarify the mechanistic pathways linking PFAS exposure to clinical cardiovascular outcomes. Full article

Emerging contaminants (ECs) encompass a wide spectrum of pollutants, from endocrine disruptors and persistent organic pollutants to microplastics and pharmaceutical residues. These contaminants often exhibit distinct chemical and physical properties compared with traditional pollutants and potentially pose risks to human health, especially as they have become pervasive in environmental and biological systems. ECs can also pose a significant threat to cardiovascular health, as they may target the ion channels that are critical to regulating cardiac excitability and contraction. However, the impact of ECs on the cardiovascular system, particularly on cardiac ion channels, remains elusive. In this review, we aim to provide an overview of the knowledge base concerning the impact of emerging contaminants on cardiac ion channels, with an emphasis on the effects of these compounds on cardiac excitability, contractility, and overall cardiovascular function. We first outline the structural and functional characteristics of ion channels, along with how these transmembrane proteins regulate cardiac physiology. Subsequently, we detail how typical ECs directly or indirectly interact with various ion channels—including sodium, calcium, potassium channels, as well as ion transporters and exchangers. Special attention is given to studies that have demonstrated cell-level responses or examined how pollutant concentration and chemical structure affect the modulation of ion channels. This review compiles recent research reports to elucidate the mechanisms by which EC exposure disrupts cardiac ion channels, potentially leading to cardiotoxicity. Moreover, the insights gathered herein illuminate critical research gaps and outline essential directions for future investigations. Full article

Emerging contaminants pose significant risks to ecosystems yet are not routinely included in standard monitoring or regulatory frameworks. Among these substances, endocrine disruptors such as β-estradiol and 17α-ethinylestradiol threaten both human and environmental health by interfering with metabolism, reproduction, and development across multiple species. These hormones are continuously released into the environment through excretion and improper disposal, and conventional water treatment processes are largely ineffective at removing them. As a result, they can accumulate in aquatic organisms and enter the human food chain. Recent studies have demonstrated that banana peel, Pleurotus ostreatus biomasses, and the nanomaterial δ-FeOOH are efficient, low-cost materials for the removal of toxic metals, suggesting their potential applicability for eliminating estrogenic compounds. Therefore, this study aimed to evaluate the removal of β-estradiol and 17α-ethinylestradiol using filters composed of banana peel and P. ostreatus biomass combined with δ-FeOOH. Hormone removal efficiency was assessed by LC-MS, and toxicity reduction was evaluated through bioassays. The results showed up to 100% removal of hormone concentrations and a significant decrease in sample toxicity, indicating that this filtration system represents a safe and effective alternative for removing organic contaminants from water. Full article

The molecular mechanism underlying male reproductive toxicity associated with Perfluorooctanoic acid (PFOA), a persistent environmental endocrine disruptor (EDC), has not yet been fully elucidated. Six-week-old male C57BL/6 mice were treated with PFOA by oral gavage at 0, 1.25, 5, 10, and 20 mg/kg/day for 35 days to explore its toxic effects on the male reproductive system and the underlying mechanisms. Analyses of semen quality, testicular histopathology, and blood–testis barrier (BTB) integrity revealed that PFOA caused dose-dependent structural and functional damage to the BTB, leading to markedly reduced semen quality. Based on transcriptomic sequencing and differential gene enrichment analysis, the glycolytic pathway was identified as a key regulatory target for PFOA-induced damage to the reproductive system. Further validation revealed that PFOA exposure inhibited glycolysis-related enzymes (Hexokinase 1 (HK1), Glucose Transporter 1 (GLUT1), and Lactate Dehydrogenase A (LDHA)), reduced lactate production and ATP synthesis, lowered Pan-Kla and H3K18la levels, and diminished H3K18la enrichment at the Hk1, Glut1, and Ldha promoters, whereas exogenous sodium lactate reversed these changes. This study is the first to identify the “glycolysis–lactate–H3K18la” chain as a key regulator in PFOA-induced BTB damage and spermatogenesis impairment, offering a new theoretical foundation for understanding EDC-induced male reproductive toxicity. Full article

Endocrine-disrupting chemicals (EDCs) are a diverse group of environmental pollutants capable of interfering with hormonal and immune system regulation. In recent years, increasing concern has been raised about the effects of chemicals, including bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), insecticides, and parabens, on maternal and fetal health, primarily due to their widespread exposure in human populations. Pregnancy represents a critical window characterized by tightly regulated hormonal and immunological adaptations. Emerging evidence suggests that EDC exposure during this period may alter maternal microbiota, disrupt immune responses, and interfere with endocrine signaling. These changes may increase susceptibility to bacterial and viral infections, including bacterial vaginosis, urinary tract infections, and intrauterine infections, all of which are associated with adverse pregnancy outcomes. This review summarizes the current evidence on the sources and mechanisms of exposure to endocrine disruptors during pregnancy and examines the potential biological pathways linking endocrine disruption to the development of infections. Particular emphasis is placed on the interactions between immune regulation, hormonal signaling, and changes in the microbiome, which may contribute to increased susceptibility to infections. A deeper understanding of these complex mechanisms is critical to improve risk assessment, develop effective public health strategies, and ultimately protect maternal and fetal health in an environment of increasing chemical exposure. A literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including studies published up to January 2026. Full article

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

Disinfection byproducts (DBPs) are ubiquitous contaminants formed during drinking water treatment and are traditionally regulated based on cytotoxic and genotoxic endpoints. However, evidence suggests that DBPs may also act as metabolic disruptors interfering with hepatic metabolic pathways. This study investigates the early metabolic disruption and steatogenic effects of four regulated DBPs, bromoform (BR), bromodichloromethane (BDCM), monochloroacetic acid (MCA), and dichloroacetic acid (DCA), using the human hepatic cell models HepG2 (derived from hepatocellular carcinoma) and HUH7 (derived from hepatoblastoma). Cells were exposed to a broad concentration range (1 pM–100 µM) to capture both sub-cytotoxic and mechanistically informative responses at low, environmentally relevant levels. Effects on lipid and sterol metabolism were assessed through the transcriptional modulation of a panel of nuclear receptors (AHR, PXR, RXR, and LXR) and the sterol regulatory enzyme HMG-CoA reductase (HMGCR) as well as intracellular lipid accumulation; cytotoxicity and oxidative stress endpoints were concurrently evaluated. All DBPs tested induced significant, dose-dependent alterations in nuclear receptor signaling and also promoted lipid accumulation in the low-concentration range and without concurrent cytotoxicity; conversely, oxidative stress responses were limited or absent, and HMGCR emerged as a sensitive target, albeit with different patterns (upregulation by BR and MCA, and downregulation by BDCM and DCA). Relevant substance-specific aspects were also observed for other transcriptional targets, e.g., PXR upregulation was particularly evident for BR and BCDM while DCA downregulated the tested receptors. DBP-induced lipid accumulation was more pronounced in HUH7. Regulated DBPs can elicit early steatogenic and metabolic effects even at concentrations below current regulatory thresholds. The findings highlight that endocrine–metabolic disruption should be considered as a relevant endpoint in DBP risk assessment. Full article

The ovaries are crucial reproductive organs that regulate the menstrual cycle and support pregnancy through the production of steroid hormones. They are highly susceptible to various environmental pollutants, which can lead to ovarian disorders. Luteal phase defect (LPD) and premature ovarian failure (POF) are common ovarian disorders in women. In this study, we integrate network toxicology with molecular docking and molecular dynamics simulations to elucidate the toxicological mechanisms of Benzo(a)pyrene (BaP), a widespread endocrine disruptor, in LPD and POF. Through systematic data mining of the GeneCards and OMIM databases, we identified 1336 targets associated with LPD and 2066 targets related to POF, as well as 220 BaP targets. Venn diagram analysis revealed 36 potential targets for BaP-induced LPD and 43 for BaP-induced POF. GO and KEGG enrichment analyses suggest that BaP-induced LPD and POF may share toxicological mechanisms. PPI network visualization indicated that EGFR, ESR1, and STAT3 are critical common targets for BaP-induced LPD and POF. Molecular docking and molecular dynamics simulations revealed that BaP exhibits strong binding affinity with all three core genes. In KGN cells modeling LPD and POF phenotypes, cellular experiments confirmed that BaP downregulated EGFR and ESR1 expression while upregulating STAT3 expression, thereby supporting the reliability of these targets in BaP-induced ovarian dysfunction. These findings provide insights into BaP-induced reproductive toxicity and offer a foundation for targeted clinical interventions to mitigate the effects of environmental pollutants on women’s reproductive health. Full article

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

Background/Objectives: Ram fertility is essential for sheep production, influenced by genetic, physiological, behavioral, and environmental factors. This narrative review synthesizes findings from over 190 peer-reviewed publications to evaluate the phenotypic indicators, genetic architecture, molecular candidates, and management conditions influencing testicular development, semen quality, and reproductive performance in rams. Methods: A narrative synthesis of peer-reviewed studies was conducted, integrating findings from quantitative genetics, genome-wide association studies, transcriptomics, and controlled environmental and management experiments. Emphasis was placed on studies evaluating fertility-related traits across breeds, ages, and production systems. Results: Recent genomic and transcriptomic studies have identified potential biomarkers (e.g., IGF1, IGFALS, FOXO1) and gene networks linked to ram fertility, including semen quality, scrotal circumference, and endocrine regulation. For instance, genome-wide association studies (GWASs) have identified candidate genes such as SLC2A8 and MAPK3, which are associated with spermatogenesis and semen quality. Additionally, Y-linked SNPs such as ZFY16: g.146 C > T have been linked to testicular development. Genetic potential is heavily modulated by environmental constraints. Heat stress emerges as a disruptor of testicular thermoregulation, with recent evidence highlighting the vulnerability of spermatogenesis even in adapted breeds. Management interventions, specifically nutritional supplementation and hormonal modulation via melatonin, are discussed as effective strategies to mitigate environmental impacts. Conclusion: Improving ram fertility will require an approach that prioritizes phenotypic traits supported by candidate genes identified through transcriptomic analyses and GWASs. Integrating these genetic tools together with cost-effective nutritional and hormonal management strategies can further improve semen quality, libido, and testicular traits, thereby enhancing fertility gains while maintaining sheep breed adaptability across production systems. Full article

A significant and persistent issue in assisted reproduction is recurrent implantation failure (RIF), which is often observed even after the transfer of embryos of high morphological and/or genetic quality. Accumulating data suggest that exposure to chemicals with endocrine-disrupting effects (EDCs) may be associated with adverse implantation outcomes. Many environmentally widespread substances have the potential to interfere with the regulation of the endocrine system, affecting critical mechanisms involved in implantation, such as endometrial receptivity, steroid hormone receptor signaling, immune tolerance at the maternal–fetal interface, and the epigenetic regulation of genes that are essential for successful implantation. Experimental studies have shown that exposure to EDCs can alter gene expression in the endometrium, inflammatory pathways, and the dynamics of early embryonic development, while clinical and epidemiological data have associated increased levels of EDCs in the body with lower implantation rates in assisted reproductive technology (ART) cycles. This narrative review examines the implications of these findings in reproductive medicine, summarizes recent experimental and clinical data, and highlights the molecular mechanisms linking exposure to endocrine disruptors with recurrent implantation failure. Recognizing environmental chemical exposure as a potentially modifiable risk factor may offer new perspectives for the prevention of RIF and the development of more personalized therapeutic strategies. Full article

Background: Mammary ductal hyperplasia represents a spectrum of benign proliferative breast lesions, some of which pose elevated risks for malignant transformation into ductal carcinoma in situ and invasive breast cancer. This narrative review explores why only specific types, particularly those with atypia, exhibit higher progression potential, synthesizing epidemiologic, histopathologic, molecular, and environmental insights. Methods: We reviewed key literature from databases, including PubMed, focusing on classification, risk stratification, genetic/epigenetic mechanisms, tumor microenvironment dynamics, and modifiable factors influencing progression. Results: Benign breast lesions are categorized into non-proliferative, proliferative without atypia, and proliferative with atypia, such as atypical ductal hyperplasia and atypical lobular hyperplasia. Atypia represents a morphologic continuum toward low-grade ductal carcinoma in situ, driven by genetic alterations, epigenetic reprogramming, and changes in the tumor microenvironment, including stromal remodeling, immune infiltration, hypoxia-induced angiogenesis, and extracellular matrix degradation. Dietary factors, such as high-fat intake and obesity, exacerbate progression through inflammation, insulin resistance, and adipokine imbalance, while environmental toxins, including endocrine disruptors, pesticides, and ionizing radiation, amplify genomic instability. Conclusions: Understanding differential risks and mechanisms underscores the need for stratified surveillance, biomarker-driven interventions, and lifestyle modifications to mitigate progression. Future research should prioritize molecular profiling for personalized prevention in high-risk hyperplasia. Full article

Background: Exposure to environmental pollutants, especially endocrine-disrupting chemicals, disproportionately affects vulnerable populations like pregnant women, lactating mothers, and preterm infants. This study aimed to assess the detection patterns of DiNP-, DEP-, and DEHP-related metabolites in maternal urine and breast milk, examine agreement between matrices, and explore maternal factors associated with phthalate exposure. Methods: Fifty-five mothers who delivered at ≤32 gestational weeks and whose infants were hospitalized in the Neonatal Intensive Care Unit (NICU) were enrolled. Breast milk and urine samples were analyzed using a validated isotope-dilution LC–MS/MS method. Urinary phthalate metabolite concentrations were adjusted for specific gravity. Linear mixed-effects models with a random intercept for mother were used to examine associations between urinary and breast milk phthalate metabolite concentrations, assess temporal changes, and evaluate the influence of breast milk lipid content. Results: DEHP and DiNP metabolites were detected in nearly all maternal urine samples. Breast milk contained predominantly primary metabolites (MEHP and MiNP), while secondary oxidative metabolites were rarely detected. Urine concentrations consistently exceeded breast milk concentrations. Urinary and breast milk phthalate concentrations were not correlated across sampling periods, indicating limited matrix concordance. Conclusions: Mothers of very preterm infants experience sustained phthalate exposure in the postpartum period; however, limited metabolite transfer to breast milk indicates that maternal urine remains the preferred biomonitoring matrix for assessing systemic phthalate exposure. Breast milk phthalate profiles exhibit compound-specific temporal changes and appear largely independent of concurrent urinary exposure biomarkers. Full article

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental endocrine disruptors (EDCs) that enter the human body through respiratory, digestive, and dermal exposure. Prolonged exposure has been associated with adverse health outcomes, including carcinogenicity, mutagenicity, and reproductive toxicity. However, whether genetic variation in apoptosis-related pathways modifies the reproductive effects of PAH exposure remains unclear. To investigate gene-environment interactions between urinary PAH metabolites and polymorphisms in apoptosis-related genes in relation to sperm apoptosis, we conducted a cross-sectional study involving 176 male participants from an infertility clinic in Wuhan, China, who completed structured questionnaires and provided biological samples. Ten OH-PAH metabolites in repeated urine samples were measured, along with genotyping of single-nucleotide polymorphisms (SNPs) at apoptosis-related genes (Fas, FasL, and caspase-3) in whole blood DNA, and sperm apoptosis. Multivariable linear regression evaluated the interaction between urinary OH-PAH levels and apoptotic gene SNPs on apoptotic sperm, with genotype-stratified analyses. PAH exposure appeared to interact with SNPs in FasL rs763110, Fas rs2234767, and caspase-3 rs12108497 to jointly influence sperm cell apoptosis. Specifically, for the FasL rs763110, higher 9-OHFlu was associated with fewer viable sperm and more apoptotic sperm, and this association was more pronounced among CC genotype homozygotes. For the caspase-3 rs12108497, higher 2-OHFlu was associated with more dead sperm, and this association was significant among TC and TC/CC genotypes. These findings suggest that genetic variation in apoptosis-related genes may modify susceptibility to PAH-induced sperm apoptosis, highlighting the importance of gene–environment interactions in male reproductive toxicity. Full article