Reproductive toxicology最新文献

{"title":"Metabolic activation of pentachlorophenol: TCBQ as a potent inhibitor of gonadal steroidogenesis via 3β-hydroxysteroid dehydrogenase NAD+ binding-site thiolalkylation","authors":"Yao Lv ,&nbsp;Jingwei Zhang ,&nbsp;Ming Su ,&nbsp;Shun Lu ,&nbsp;Shaowei Wang ,&nbsp;Ren-shan Ge ,&nbsp;Huitao Li","doi":"10.1016/j.reprotox.2025.109115","DOIUrl":"10.1016/j.reprotox.2025.109115","url":null,"abstract":"<div><div>Pentachlorophenol (PCP) is a pesticide and persistent endocrine disruptor. This study examined how PCP and its metabolite tetrachloro-1,4-benzoquinone (TCBQ) inhibit human (h3β-HSD2) and rat (r3β-HSD1) gonadal steroidogenic enzymes. <em>In vitro</em> assays using human KGN cells and rat testicular microsomes showed PCP moderately inhibited h3β-HSD2 (IC₅₀: 22.55 μM, mixed inhibitor), while TCBQ was more potent (IC₅₀: 6.42 μM). PCP (25–50 μM) significantly reduced progesterone in KGN cells, whereas TCBQ suppressed it at ≥ 1 μM. In rats, PCP weakly inhibited r3β-HSD1 (IC₅₀: 32.03 μM), but TCBQ was far stronger (IC₅₀: 41 nM, mixed/noncompetitive). Molecular docking revealed both compounds bind to the enzyme’s steroid/NAD⁺ site, with TCBQ covalently attaching to Cys123 via Michael addition. Dithiothreitol (DTT) partially reversed TCBQ’s inhibition but not PCP’s, suggesting differing mechanisms. Findings indicate PCP’s metabolic activation to TCBQ drives its stronger endocrine-disrupting effects, highlighting TCBQ’s role as a potent 3β-HSD inhibitor in both species.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109115"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal exposure to the pesticides chlorpyrifos and 2,4-Dichlorophenoxyacetic acid is associated with circulating levels of reproductive hormones in healthy infant girls","authors":"Anna-Patricia Iversen ,&nbsp;Jessica Bruun ,&nbsp;Lars Christian Lund ,&nbsp;Sarah Bakkær Munk Andreasen ,&nbsp;Þórhallur Ingi Halldórsson ,&nbsp;Anders Juul ,&nbsp;Hanne Frederiksen ,&nbsp;Anna-Maria Andersson ,&nbsp;Casper P. Hagen ,&nbsp;Flemming Nielsen ,&nbsp;Marianne Skovsager Andersen ,&nbsp;Tina Kold Jensen ,&nbsp;Helle Raun Andersen","doi":"10.1016/j.reprotox.2025.109112","DOIUrl":"10.1016/j.reprotox.2025.109112","url":null,"abstract":"<div><h3>Background</h3><div>Pesticides are widespread in the environment and suspected endocrine disruptors that may interfere with sex hormones. Following the chlorpyrifos ban in 2020, use of alternative pesticides has increased; 2,4-Dichlorophenoxyacetic acid (2,4-D) remains widely used. This study examined the association between maternal pesticide exposure and pituitary, gonadal, and adrenal hormones in offspring during infancy.</div></div><div><h3>Methods</h3><div>We recruited pregnant women from 2010 to 2012 in the Odense Child Cohort, including 489 mother-child pairs. Maternal urinary concentrations of the generic pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA), the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol (TCPY), and the herbicide 2,4-D were measured at gestational week 28. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), estrone (E1), estradiol (E2), 17-hydroxyprogesterone (17-OHP), Androstenedione (Adione), and Dehydroepiandrosterone sulfate (DHEAS) were assessed in infancy. Associations between prenatal pesticide exposure and offspring reproductive hormones (expressed as age- and sex-specific standard deviation (SD) scores) were assessed using multivariate linear regression.</div></div><div><h3>Results</h3><div>In girls, higher maternal urinary TCPY and 2,4-D concentrations were associated with lower LH (-0.07 SD, 95 % CI: − 0.13; − 0.01 and − 0.06 SD, 95 % CI: − 0.11; − 0.02, per 1 µg/L increase, respectively); there were trends towards associations between 3-PBA, TCPY, 2,4-D and lower LH, FSH, E1 and E2, respectively. No associations were seen in boys.</div></div><div><h3>Conclusion</h3><div>In this low-exposed cohort, prenatal exposure to chlorpyrifos and 2,4-D may affect the reproductive hormones in girls, but not boys, during minipuberty, which may have long-term implications. This is of public health concern given the fact that &gt; 90 % of participants were exposed.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109112"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycine improves PFOS induced inhibition of in vitro development of porcine oocytes by reducing ferroptosis","authors":"Xiaoqing Sun ,&nbsp;Ran Teng ,&nbsp;Ning Xu ,&nbsp;Enbo Zhang ,&nbsp;Xingfu Chen ,&nbsp;Suo Li","doi":"10.1016/j.reprotox.2025.109099","DOIUrl":"10.1016/j.reprotox.2025.109099","url":null,"abstract":"<div><div>Perfluorooctanesulfonic acid (PFOS) is an environmental pollutant of significant concern in the field of reproductive health. Our previous studies have confirmed that PFOS can induce mitochondria-dependent ferroptosis, thereby impairing oocyte maturation and embryonic development. This study investigated the protective effects of exogenous glycine (Gly) supplementation—an important endogenous antioxidant—on PFOS-induced damage in porcine oocytes. Initially, we found that Gly alleviated the adverse effects of PFOS exposure on oocyte maturation quality and blastocyst development. Further studies demonstrated that exogenous Gly supplementation significantly improved mitochondrial function, increased adenosine triphosphate (ATP) and glutathione (GSH) levels, and markedly reduced reactive oxygen species (ROS) levels, indicating that Gly attenuates PFOS-induced mitochondrial oxidative damage in oocytes. Moreover, PFOS exposure significantly decreased ferritin levels, dysregulated iron (Fe²⁺) homeostasis, and triggered ferroptosis—all of which were ameliorated by exogenous Gly supplementation. Gly also mitigated PFOS-induced abnormalities in the expression of ferroptosis-related genes such as <em>PCBP1</em>, <em>PCBP2</em>, <em>GCLC</em>, and <em>SLC7A11</em>. In addition, the aberrant expression of Nrf2, PEX19, <em>GPX4</em>, and malondialdehyde (MDA) caused by PFOS exposure was reversed after Gly supplementation. In conclusion, glycine enhances antioxidant capacity by regulating redox balance, inhibits lipid peroxidation, improves ferroptosis-related conditions, and thereby mitigates the detrimental effects of PFOS exposure on in vitro oocyte maturation and early embryonic development.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109099"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network toxicology and machine learning reveal the impact of acetyl tributyl citrate on erectile dysfunction and identify cathepsin S as a critical regulator","authors":"Zhiyu Liu ,&nbsp;Yuqi Li ,&nbsp;Juan Wang ,&nbsp;Yang Zeng ,&nbsp;Qilong Wu ,&nbsp;Xinyao Zhu ,&nbsp;Tao Zhou ,&nbsp;Qingfu Deng","doi":"10.1016/j.reprotox.2025.109101","DOIUrl":"10.1016/j.reprotox.2025.109101","url":null,"abstract":"<div><h3>Background</h3><div>Erectile dysfunction (ED), a common male sexual disorder, may be associated with acetyl tributyl citrate (ATBC) exposure. EDCs can interfere with hormonal signaling and physiological homeostasis, but their specific roles and mechanisms in contributing to ED remain inadequately elucidated.</div></div><div><h3>Methods</h3><div>Network toxicology and enrichment analyses were utilized to identify potential targets and signaling pathways involved in ATBC-induced ED. A protein-protein interaction (PPI) network was constructed, and key regulatory molecules were identified using EPC, MNC, Betweenness, and Degree algorithms. Single-cell sequencing was conducted to analyze the expression profiles of target genes in penile corpus cavernosum tissue. Five machine learning algorithms were applied to pinpoint core targets and evaluate the association between ATBC and ED. Finally, molecular docking validated the binding characteristics between ATBC and the target proteins.</div></div><div><h3>Results</h3><div>A total of 71 potential targets were identified, and 11 key genes were determined through PPI network construction and topological analysis. Single-cell sequencing revealed tissue-specific expression patterns of these targets, while machine learning identified cathepsin S (CTSS) as the core target. Molecular docking confirmed a stable binding affinity between ATBC and CTSS. In vitro experiments further demonstrated the impact of ATBC on endothelial cell function and CTSS expression.</div></div><div><h3>Conclusions</h3><div>This study systematically elucidates how ATBC regulates CTSS expression, impacting endothelial function and contributing to ED. The findings advance understanding of environmental endocrine disruptors in male sexual dysfunction and highlight novel molecular targets for prevention and intervention.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109101"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide endotoxin triggers inflammatory responses that disrupt granulosa cell function and alter cell growth dynamics","authors":"Briza Castro ,&nbsp;Jeffrey F. Dominguez Arellanes ,&nbsp;Charles B. Shuster ,&nbsp;Sergio A. Soto-Navarro ,&nbsp;Craig A. Gifford ,&nbsp;Jennifer A. Hernandez Gifford","doi":"10.1016/j.reprotox.2025.109111","DOIUrl":"10.1016/j.reprotox.2025.109111","url":null,"abstract":"<div><div>Gram-negative bacterial release of the endotoxin lipopolysaccharide (LPS) perturbs granulosa cell signaling resulting in reduced estradiol synthesis and disrupted folliculogenesis thereby compromising fertility. While elevated LPS from clinical infections impairs female reproduction, the effects of low-level LPS from subclinical infections remain poorly defined. This study examined increasing LPS concentrations on granulosa cell growth dynamics, immune responses, and steroidogenesis. Human granulosa (KGN) cells were cultured for 48 h with vehicle or LPS (0.0001–10 µg/mL), with or without follicle-stimulating hormone (FSH). No significant LPS × FSH interaction was detected on steroidogenic gene expression (all <em>P</em> ≥ 0.95). LPS increased <em>STAR</em> mRNA abundance with the greatest expression at 10 µg/mL LPS compared to lower concentrations (<em>P</em> ≤ 0.04). Cells treated with FSH demonstrated decreased <em>CTNNB1</em> (<em>P</em> = 0.0007) and increased <em>CYP19A</em> expression (<em>P</em> = 0.003), while LPS alone had no effect on either gene. Pro-inflammatory gene expression was affected by LPS. LPS dose-dependently increased <em>IL-6</em>, <em>IL-8</em> and <em>MCP-1</em> expression in KGN cells, at 1 and 10 µg/mL, while <em>NF-κB</em> expression was unaffected by LPS, FSH or their interaction. Media progesterone (P₄; <em>P</em> = 0.99) and estradiol (E₂: <em>P</em> = 0.50) concentrations were unaffected by LPS. Live imaging revealed no change in cell confluency at 0.01 µg/mL or 0.1 µg/mL LPS, while 1 µg/mL and 10 µg/mL LPS reduced confluency over 48 h (<em>P</em> = 0.06 and <em>P</em> = 0.02, respectively). KGN cells responded to low-dose LPS with elevated pro-inflammatory cytokine expression. In conclusion, higher LPS concentrations suppress granulosa cell proliferation, an effect mitigated by FSH, indicating that gonadotropic input may protect against LPS-induced ovarian dysfunction.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109111"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of rutin against docetaxel-induced testicular damage in rats: Effects on antioxidant defence, apoptosis and autophagy","authors":"Sadık Küçükgünay ,&nbsp;Halime Tozak Yildiz ,&nbsp;Oya Korkmaz ,&nbsp;Memiş Bolacali ,&nbsp;Mustafa Numan Bucak ,&nbsp;Hasan Ali Çay ,&nbsp;Şöhret Güler","doi":"10.1016/j.reprotox.2025.109110","DOIUrl":"10.1016/j.reprotox.2025.109110","url":null,"abstract":"<div><div>Docetaxel (DTX), a widely used chemotherapeutic agent, is known for its effectiveness in cancer treatment but also for its toxic effects on healthy tissues, particularly the male reproductive system. This study aimed to investigate the protective role of rutin, a natural flavonoid with known antioxidant and anti-apoptotic properties, against DTX-induced testicular damage in rats. Thirty-six adult male Wistar rats were randomly divided into six groups: Control, Rutin 50 mg/kg (R50), Rutin 100 mg/kg (R100), DTX, DTX+R50, and DTX+R100. A single dose of DTX (30 mg/kg, i.p.) was administered, while rutin was given orally for 7 days. On day eight, all animals were sacrificed. Sperm parameters (concentration, motility, morphology, chromatin integrity), serum testosterone and inhibin B levels, and testicular MDA and SOD levels were assessed. Histological evaluations were conducted using hematoxylin-eosin staining, Johnsen scoring, and tubule diameter measurements. Immunohistochemical analysis of Caspase-3, Bax, Bcl-2, mTOR, ULK1, and Atg13 was performed. Data were analyzed, and p &lt; 0.05 was considered statistically significant. DTX significantly impaired sperm motility and hormone levels, increased oxidative stress, and caused histological damage in the testes (p &lt; 0.001). Rutin, especially at 100 mg/kg, ameliorated these effects, restoring sperm function, hormonal balance, and testicular architecture. Furthermore, rutin reduced DTX-induced apoptosis and autophagy marker expression while preserving Bcl-2 levels (p &lt; 0.001). DTX induces structural and functional impairments in testicular tissue via oxidative stress, apoptosis, and autophagy. Rutin demonstrated a dose-dependent protective effect, suggesting its potential as a supportive agent against chemotherapy-induced gonadotoxicity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109110"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145542390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling polycyclic aromatic hydrocarbons exposure and female infertility risk in southern China: An integrated epidemiologic and network toxicology approach","authors":"Chuhang Lin ,&nbsp;Qian Chen ,&nbsp;Qianqian Xie ,&nbsp;Haiying Li ,&nbsp;Xiaomei Wu ,&nbsp;Xiaoxiao Lin ,&nbsp;Lijun Wang ,&nbsp;Xingming Zhong ,&nbsp;Lei Tan ,&nbsp;Chunxia Jing","doi":"10.1016/j.reprotox.2025.109108","DOIUrl":"10.1016/j.reprotox.2025.109108","url":null,"abstract":"<div><div>The relationship between polycyclic aromatic hydrocarbons (PAHs) exposure and female infertility (FI) remains unclear, particularly regarding mixed PAH exposures. This study aimed to investigate the association between individual and mixed PAH exposures and FI by integrating epidemiological and network toxicological approaches. A case-control study was conducted involving 83 infertile patients and 272 non-infertile controls in Guangdong Province, China. Three statistical models were applied to assess the effects of eight urinary hydroxylated-PAHs (OH-PAHs) metabolites on FI. Network toxicology analysis was utilized to identify common genes, potential pathways, and key targets. After adjusting for potential confounders, 3-OHFLU and 2-OHPHE were significantly associated with an increased risk of FI, with 3-OHFLU identified as the predominant risk factor (OR [95 % CI]: 1.92 [1.42, 2.69]). Mixture analysis revealed a positive association between mixed OH-PAHs and FI risk, with 3-OHFLU contributing the most. Based on network toxicology analysis, we propose a potential mechanism: PAHs exposure may activate the TNF signaling pathway, which could trigger an inflammatory response, potentially altering AKT1 expression via the PI3K-Akt pathway. This might lead to reduced cell survival, promoted oocyte apoptosis, and ultimately contribute to FI. These findings indicate that mixed PAHs exposure increases the risk of FI, with 3-OHFLU identified as the predominant contributing factor and the TNF signaling pathway serving as a potential underlying mechanism. Further longitudinal studies are needed to validate these results.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109108"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between per- and polyfluoroalkyl substances and reproductive outcomes among women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment","authors":"Linjie Yang ,&nbsp;Rongju Liu ,&nbsp;Kaihui Li ,&nbsp;Siyan Chen ,&nbsp;Lei Tan ,&nbsp;Xijin Xu ,&nbsp;William Au ,&nbsp;Xia Huo","doi":"10.1016/j.reprotox.2025.109107","DOIUrl":"10.1016/j.reprotox.2025.109107","url":null,"abstract":"<div><div>Exposure to per- and poly-fluoroalkyl substances (PFAS) has been reported to impair fertility in experimental models. However, studies on female reproductive outcomes are limited to a few legacy PFAS. This study linked exposure to various PFAS with reproductive outcomes in women undergoing IVF/ICSI. A total of 275 women were recruited, and plasma concentrations of 17 PFAS were quantified. Based on analysis using the adjusted generalized linear models, an increase in the quartile of 6:2Cl-PFESA was associated with a decrease in the number of 2PN zygotes [9.33, 95 %CI: (3.63, 15.03)] and 2PN cleavage embryos [9.20, 95 %CI: (3.57, 14.83)]. Higher quartiles of 8:2Cl-PFESA were associated with lower fertilization rate [67.44, 95 %CI: (47.91, 86.97)]. Long-chain PFAS (PFUnDA, PFTrDA, PFTeDA) were negatively correlated with oocytes quantity and embryo quality. PFHxS was associated with a reduced number of high-quality blastocysts [55.72, 95 %CI: (17.72, 93.72)]. Increased PFOA levels were associated with lower number of patients who achieved biochemical and clinical pregnancy outcomes. Quantile G-computation (QGC) showed that mixed PFAS exposures were negatively correlated with the number of oocytes retrieved, mature oocytes, 2PN zygotes, 2PN cleavage embryos, high-quality embryos, high-quality blastocysts and the number of blastocysts formed. Our results indicate that exposure to a variety of PFAS was inversely associated with the number of extracted oocytes, mature oocytes, 2PN zygotes, 2PN cleavage embryos, high-quality embryos, and high-quality blastocysts among women undergoing IVF/ICSI treatment. Our study highlights the potential reproductive toxicity of PFAS and the need for further research to determine its impact on human fertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109107"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro- and nanoplastics: Emerging environmental threats to the Developmental Origins of Health and Disease","authors":"Lauren Rae Gladwell,&nbsp;Jhanvi Karthik,&nbsp;Laura Packer,&nbsp;Sunil Venkategowda,&nbsp;Mahua Choudhury","doi":"10.1016/j.reprotox.2025.109098","DOIUrl":"10.1016/j.reprotox.2025.109098","url":null,"abstract":"<div><div>Environmental exposure to micro- and nanoplastics (MNPs) can have significant impacts on the development of chronic health conditions in children and adults. MNPs are byproducts generated from the ubiquitous and daily use of plastics. A growing body of literature points to MNPs’ affecting human metabolic and reproductive health, yet research into their potential impacts is still in its infancy. Due to recent evidence demonstrating accumulation of MNPs within human metabolic and reproductive tissues, their potential for inducing physiological and epigenetic dysregulations is postulated. This is especially critical for future generations as epigenetic disturbances within individuals can be inherited. Currently, the mechanisms for how MNPs exert their effects are still under investigation. In this scenario, the developmental origins of health and disease (DOHaD) offers insight on the influence of environmental exposures in the periconceptual, fetal, and early phases of life towards the development of noncommunicable diseases later in life. DOHaD investigates these interactions through an epigenetic lens as epigenetics bridges environmental exposures and changes in gene expression outside of the DNA sequence itself. In this review, we provide an overview on current research that describes MNPs’ contribution towards the development of metabolic and reproductive dysfunction as well as their potential to impact future generations through the DOHaD paradigm possibly mediated by epigenetic modifications.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109098"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First evidence of legacy and emerging per- and polyfluoroalkyl substances (PFAS) in the follicular fluid of a cohort of North Carolina in vitro fertilization (IVF) patients","authors":"S.S. Boney ,&nbsp;C. Christen ,&nbsp;B.A. Wetmore ,&nbsp;A.S. Murr ,&nbsp;D. Raburn ,&nbsp;S.L. Young ,&nbsp;C. Abraham ,&nbsp;T.E. Stoker","doi":"10.1016/j.reprotox.2025.109102","DOIUrl":"10.1016/j.reprotox.2025.109102","url":null,"abstract":"<div><div>Despite widespread per- and polyfluoroalkyl substances (PFAS) contamination in North Carolina (NC), such as in the Cape Fear region, and documented detection in drinking water and serum, little is known about their accumulation in human follicular fluid (FF)—a critical microenvironment for oocyte maturation. Therefore, the aim of this study was to quantify PFAS in the FF of 86 women undergoing <em>in vitro</em> fertilization (IVF) in NC. Using targeted analysis, we measured 23 PFAS including legacy, alternatives, and emerging ether compounds. PFAS were detected in all samples, with the highest levels in perfluoroalkyl sulfonic acids (PFSAs) such as PFHxS and PFOS (2.36 and 1.28 ng/mL). Detection frequencies varied by chemical class, with legacy perfluoroalkyl carboxylic acids (PFCAs) and PFSAs detected more often than emerging alternatives. Interestingly, hexafluoropropylene oxide dimer acid (GenX) was detected in 88 % of samples and this PFAS is not frequently detected in human serum. Three to 16 analytes were detected per patient in a range of 0.5–12.8 ng/mL. The cumulative PFAS load was not significantly different between patients with and without an infertility diagnosis, though individual variability was high. This is the first study to examine PFAS in FF in NC and confirms that both legacy and alternative PFAS can cross the blood–follicle barrier to accumulate in FF. This study detected several compounds at a high frequency that have not been previously reported in NC serum, including PFDS, PFTrA, and GenX.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109102"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}