Reproductive toxicology最新文献

{"title":"Effects of dexamethasone on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats","authors":"Jie Zhao ,&nbsp;Xianyi Zhou ,&nbsp;Hao Yu ,&nbsp;Abdul Quddus ,&nbsp;Xin Liu ,&nbsp;Dagan Mao","doi":"10.1016/j.reprotox.2026.109166","DOIUrl":"10.1016/j.reprotox.2026.109166","url":null,"abstract":"<div><div>This study aimed to investigate effects of dexamethasone (Dex) on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats. Rats aged 28 days were treated with PMSG and hCG to obtain amounts of <em>corpora lutea</em>, followed by injections of Dex (Dex group) or saline (Control, Con group) for 7 days. Serum was collected to detect biochemical indices with corresponding kits and progesterone (P4) levels by RIA. Ovaries were collected for HE, IHC and TUNEL analysis, and genes and proteins associated with steroidogenesis and apoptosis, including PKA/CREB/PPARG members using real-time PCR and western blotting, respectively. Results showed that Dex treatment increased serum triglyceride and glucose levels (<em>P</em> &lt; 0.05), and decreased high－density lipoprotein cholesterol and low－density lipoprotein cholesterol levels (<em>P</em> &lt; 0.05). Dex treatment increased serum P4 level (<em>P</em> &lt; 0.05), as well as ovarian mRNA abundances of <em>Star</em> and <em>Cyp11a1</em> (<em>P</em> &lt; 0.05), and protein levels of StAR and HSD3B (<em>P</em> &lt; 0.05); Dex also increased the Bax/Bcl-2 ratio at both mRNA and protein levels (<em>P</em> &lt; 0.05), with a greater incidence of apoptosis confirmed by BAX immunostaining and TUNEL assay. Dex treatment increased the mRNA abundances and protein levels of PKA/CREB/PPARG members (<em>P</em> &lt; 0.05). IHC analysis showed that PPARG was localized in the nuclei as well as cytoplasm of luteal cells. Overall, Dex concurrently stimulated luteal steroidogenesis and apoptosis, likely by the activation of PKA/CREB/PPARG pathway, providing novel insights into stress-related glucocorticoids on luteal function, and reproductive health in mammals under stress or therapeutic glucocorticoid treatment.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109166"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952137","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":"Reduced food consumption triggers abortion in antibiotic-treated pregnant rabbits: Insights from a pair-feeding study","authors":"Toshiki Matsuoka ,&nbsp;Yoshiko Ohshima ,&nbsp;Kumi Honda ,&nbsp;Makoto Shirai ,&nbsp;Ken Sakurai ,&nbsp;Chiharu Kuwata","doi":"10.1016/j.reprotox.2026.109176","DOIUrl":"10.1016/j.reprotox.2026.109176","url":null,"abstract":"<div><div>In embryo-fetal developmental toxicity studies in rabbits, antibiotic administration is often accompanied by reduced food consumption and abortion. This study aimed to investigate whether reduced food consumption, independent of antibiotic exposure, was sufficient to induce abortion and explore potential mechanisms. Pregnant rabbits were assigned to three groups (n = 5/group): oral administration of the fluoroquinolone antibiotic DC-159a group, a pair-fed group receiving the same daily amount of diet as the DC-159a group, and a control group fed <em>ad libitum</em>. DC-159a administration from gestational days 6–18 caused a marked and sustained reduction in food consumption and abortion in all dams. Notably, all pair-fed dams also aborted. Changes in blood chemistry consistent with undernutrition were observed in both groups. Serum progesterone began to decline several days before abortion, and ovarian histopathology suggested luteal dysfunction. These findings indicate that reduced food consumption is the primary trigger of abortion in rabbits treated with DC-159a, indicating the involvement of compromised luteal function under nutritional stress.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109176"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077443","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":"Effects of paternal 5G RFR exposure on health of male offspring mice","authors":"Zhang Zhaowen ,&nbsp;Guo Ling ,&nbsp;Zhou Guiqiang ,&nbsp;Lin Jiajin ,&nbsp;Qin Tongzhou ,&nbsp;Li Jiangyi ,&nbsp;Li Jing ,&nbsp;Wang Fuli ,&nbsp;Ding Guirong","doi":"10.1016/j.reprotox.2025.109139","DOIUrl":"10.1016/j.reprotox.2025.109139","url":null,"abstract":"<div><div>With the widespread application of 5G communication technology, the potential health risks of radiofrequency radiation (RFR) have been paid much attention. Prior studies have demonstrated that the testes are highly sensitive to RFR, and notably, paternal epigenetic modifications can be transmitted to offspring, impacting their reproductive and neurobehavioral phenotypes. To investigate the intergenerational effects of paternal exposure to 5 G RFR on male offspring health, 7–8-week-old male C57BL/6 mice were randomly divided into Sham group and 4.9 GHz RFR group (16 mice per group). The mice in 4.9 GHz RFR group were exposed to 4.9 GHz RFR for 1 h/d over 42 consecutive days. Male offspring derived from exposed males and unexposed females were raised to adulthood. Anxiety and depression-like behaviors, learning and memory capabilities, sperm quality, and fertility in male offspring were assessed. Paternal testicular LRGUK gene (sperm motility-related) methylation, mRNA, and protein expression were detected. The results showed that paternal 5G RFR exposure induced anxiety-like behaviors and impaired sperm quality in F1 males, potentially associated with RFR-induced hypermethylation of paternal LRGUK gene and subsequent down regulation of its expression in offspring testes. No significant effects were observed on depression-like behaviors, cognitive performance, or fertility across F1-F2 generations. These findings indicated that paternal 5G RFR exposure induced intergenerational adverse effects on F1 males, potentially mediated by germ cell epigenetic modifications.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109139"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756196","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":"Catechin hydrate alleviates tramadol-induced ovarian and uterine injury through regulation of oxidative and ER stress, apoptosis, steroidogenesis, and hormonal imbalance","authors":"Ramazan Bülbül ,&nbsp;Hasan Şimşek ,&nbsp;Nurhan Akaras ,&nbsp;Özge Kandemir ,&nbsp;Fatih Mehmet Kandemir ,&nbsp;Cüneyt Çağlayan ,&nbsp;Aydın Genç","doi":"10.1016/j.reprotox.2025.109132","DOIUrl":"10.1016/j.reprotox.2025.109132","url":null,"abstract":"<div><h3>Aim</h3><div>This study investigated the harmful effects of tramadol (TRD) exposure on ovarian and uterine tissue, with a specific focus on oxidative stress and the damage pathways it triggers. It also aimed to establish whether catechin hydrate (CTH), a potent antioxidant flavonoid, could protect against or repair TRD-induced reproductive toxicity.</div></div><div><h3>Methods</h3><div>28 Wistar rats were randomly divided into four groups: Control, CTH, TRD, and TRD+CTH. TRD (50 mg/kg, intraperitoneal) and CTH (20 mg/kg, oral) were administered daily for a period of 14 days. Subsequent to the administration of treatment, blood, ovarian, and uterine tissues were collected for biochemical, qRT-PCR, histopathological, and immunohistochemical analyses to evaluate oxidative and ER stress, inflammation and apoptotic damage, hormonal changes, and tissue damage.</div></div><div><h3>Results</h3><div>TRD administration significantly increased oxidative stress (MDA, p &lt; 0.001), inflammation (NF-κB, TNF-α, IL-1β, p &lt; 0.001), apoptosis (Caspase-3, Bax, p &lt; 0.001), and ER stress (PERK, ATF6, p &lt; 0.001), while suppressing antioxidant parameters, Bcl-2 and steroidogenic enzyme expression (CYP11A1, CYP17A1, CYP19A1, p &lt; 0.001) and reducing serum AMH, E2, FSH, and LH levels (p &lt; 0.001). Co-administration of CTH markedly reversed these effects by restoring antioxidant and hormonal balance (p &lt; 0.05–0.001) and downregulating oxidative, inflammatory, and apoptotic markers. Histologically, CTH treatment notably improved TRD-induced ovarian and uterine degeneration, reducing inflammation, congestion, and follicular atresia while preserving tissue integrity (p &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>The findings of this study suggest that CTH may offer protective effects against TRD-induced ovarian and uterine toxicity by mitigating oxidative stress, inflammation, apoptosis, and ER stress, thereby supporting hormonal balance and tissue integrity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109132"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695765","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":"Atrazine exposure during puberty causes long-lasting neurochemical alterations and sex-dependent sexual behavior deficits in rats","authors":"L.P. Pantaleon ,&nbsp;J. Zaccarelli-Magalhães ,&nbsp;M.E.S. Brandão ,&nbsp;L.R. De-Paula ,&nbsp;G.M. RibeirO ,&nbsp;G.R. Abreu ,&nbsp;J.W.P. Muñoz ,&nbsp;J.C.B. Delorenzi ,&nbsp;A.R. Fukushima ,&nbsp;H.S. Spinosa ,&nbsp;E.L. Ricci","doi":"10.1016/j.reprotox.2025.109137","DOIUrl":"10.1016/j.reprotox.2025.109137","url":null,"abstract":"<div><div>Atrazine is one of the most used pesticides worldwide. It is detected in surface and groundwater, together with its active metabolite. In animals, atrazine’s toxic effects are neuroendocrine, behavioral, and developmental alterations, in both males and females. However, there are few studies on the effects of atrazine on an adult animal exposed during puberty. Thus, this study aims to evaluate the behavioral and neurochemical effects of atrazine exposure during puberty on adult male and female rats’ sexual behavior sphere. Wistar rats were exposed to different doses of atrazine (10, 30, or 100 mg/kg) by oral gavage from postnatal day 22–41 (period equivalent to human adolescence). The behavioral and neurochemical evaluation were conducted by analyzing body weight gain, as well as water and food intake during treatment; male sexual behavior through gait test, sexual motivation test, penile erection test, and sexual behavior test; female sexual behavior through sexual behavior test and estrous cycle evaluation; and dopaminergic and serotoninergic systems. Results showed 1) few alterations in body weight gain, as well as water and food intake during treatment in both males and females; 2) males had few alterations in sexual behavior (increase in the latency for first erection and lower number of post-ejaculatory intromissions); 3) females had no alterations of sexual behavior; and 4) both male and female had alterations in the brain dopaminergic and serotoninergic systems, with males being more responsive. Taking together these data suggests that atrazine causes long-lasting adverse effects that can affect a rat’s sexual performance.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109137"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744238","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":"Male reproductive toxicity induced by chronic dinotefuran exposure: In vivo and in silico evidence and the ameliorative role of Rosmarinus officinalis","authors":"Samah S. Arafa ,&nbsp;Ibrahim.M. Ammar ,&nbsp;Ragaa A. Eisa ,&nbsp;Mariam E. Labib ,&nbsp;Ahmed M. Atwa ,&nbsp;Marwa O. Gabr","doi":"10.1016/j.reprotox.2025.109118","DOIUrl":"10.1016/j.reprotox.2025.109118","url":null,"abstract":"<div><div>Dinotefuran (DINO), a chiral neonicotinoid insecticide, is widely used for pest control but increasing evidence suggests potential risks to non-target organisms, including mammals. This study evaluated the reproductive toxicity of chronic DINO exposure in male albino rats and assessed the ameliorative potential of <em>Rosmarinus officinalis</em> extract (RE). Male rats received DINO orally once daily at doses of 94 or 281 mg/kg for 25 consecutive weeks. DINO exposure impaired reproductive performance, as shown by significant reductions in the male mating and fertility indices, decreased testicular weight, and deterioration of sperm quality (count, motility, and viability), accompanied by increased sperm aneuploidy. Endocrine disruption was evident, with altered serum hormone profiles. Histopathological analysis revealed extensive testicular damage, and immunohistochemistry confirmed increased caspase-3 expression, reflecting enhanced apoptosis. Molecular docking supported these findings by demonstrating strong binding interactions of DINO with key enzymes and receptors involved in steroidogenesis and reproductive regulation (CYP11A1, CYP17A1, 3β-HSD, 17β-HSD, CYP19A1, caspase-3, AR, ERα/β, PRLR, TRα/β, FSHR, and LHCGR). Notably, co-treatment with RE (220 mg/kg) significantly alleviated these adverse effects, underscoring its antioxidant and ameliorative role. In conclusion, chronic DINO exposure poses substantial risks to male reproductive health, whereas RE demonstrates promising potential as a protective agent, particularly relevant in contexts of high pesticide exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109118"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622906","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":"Developmental toxicity and cytotoxic/genotoxic potential of PM10 rural extracts using Xenopus laevis embryos and A549 lung epithelial cells","authors":"Gloria Melzi ,&nbsp;Maria Battistoni ,&nbsp;Renato Bacchetta ,&nbsp;Beatrice Biffi ,&nbsp;Cristina Colombi ,&nbsp;Emanuela Corsini ,&nbsp;Francesca Di Renzo ,&nbsp;Marina Marinovich ,&nbsp;Francesca Metruccio ,&nbsp;Elena Menegola ,&nbsp;Sofia Pantaleoni ,&nbsp;Sara Valentini ,&nbsp;Gianluigi Valli ,&nbsp;Roberta Vecchi","doi":"10.1016/j.reprotox.2026.109178","DOIUrl":"10.1016/j.reprotox.2026.109178","url":null,"abstract":"<div><div>Airborne particulate matter is increasingly recognized as a hazard for developmental health. While epidemiological studies associate PM₁₀ prenatal exposure and adverse outcomes (including low birth weight and preterm birth), experimental evidence clarifying biological plausibility remains limited, especially for complex PM mixtures collected in non-urban settings. Air-quality–related developmental risks in rural areas interested by PM pollutions are underestimated. In this context, our study aimed to assess the developmental toxicity of PM₁₀ extracts collected at a rural Po Valley site, using a sensitive vertebrate embryo model. We exposed <em>Xenopus laevis</em> embryos to extracts of daytime and nighttime PM₁₀ collected over two weeks (March 2022) and evaluated lethality, teratogenicity and developmental progression with the Refined Frog Embryo Teratogenesis Assay–Xenopus (R-FETAX). In parallel, PM₁₀ filters were chemically characterized (mass, major ions, carbon fractions, and multiple elements), allowing us to model links between developmental outcomes and specific PM components. To provide a conventional toxicological benchmark, extracts were also tested in A549 human lung epithelial cells for cytotoxicity and genotoxicity. Our results show that, despite the absence of lethality or gross malformations, some PM₁₀ extracts induced statistically significant developmental delays. Modelling revealed correlations between delays and PM₁₀ mass as well as several measured analytes, with Zn and Cu displaying the clearest dose-dependent associations. Embryonic development detected subtle effects of low-level PM₁₀ exposure that were not captured by standard cytotoxicity/genotoxicity endpoints in A549 cells under the tested conditions. Collectively, these findings support the utility of a developmental model for mixture-based particulate toxicology evaluation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109178"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077481","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":"Systematic analyses uncover endocrine-disrupting chemical-responsive genes linked to endometriosis","authors":"Yanggang Hong ,&nbsp;Tangansu Zhang ,&nbsp;Jingxuan Zhou ,&nbsp;Lingfei Wang ,&nbsp;Yirong Wang ,&nbsp;Wanyi Shu ,&nbsp;Hongbo Wang ,&nbsp;Haiyan Chen","doi":"10.1016/j.reprotox.2025.109148","DOIUrl":"10.1016/j.reprotox.2025.109148","url":null,"abstract":"<div><div>Endometriosis is a chronic, estrogen-dependent disorder influenced by both genetic and environmental factors, including endocrine-disrupting chemicals (EDCs). This study aimed to identify EDC-responsive genes contributing to endometriosis risk by integrating Mendelian randomization (MR), Bayesian colocalization, and single-cell RNA sequencing (scRNA-seq). We first compiled a list of EDC-responsive genes using curated chemical-gene interaction databases. MR and Bayesian colocalization analyses were applied to integrate gene expression quantitative trait loci (eQTL) data with genome-wide association study (GWAS) data for endometriosis. We identified eight genes (<em>PRLR</em>, <em>SULT1B1</em>, <em>DIP2B</em>, <em>FBXO5</em>, <em>CDCA2</em>, <em>AGPAT1</em>, <em>PDE5A</em>, and <em>VPS13B</em>) with strong evidence for causal association and shared genetic regulation. The scRNA-seq revealed that these genes are differentially expressed across key cell types, including mesenchymal, epithelial, and smooth muscle cells. <em>PRLR</em> was enriched in mesenchymal cells, while <em>PDE5A</em> showed high expression in smooth muscle cells. The chemical-gene interaction network further highlighted specific EDCs linked to these genes, such as perfluorooctanoic acid, triphenyl phosphate, and bisphenol A. This study uncovers molecular pathways by which EDCs may influence endometriosis risk and identifies potential biomarkers and therapeutic targets. The findings also establish a scalable approach for studying gene-environment interactions in other hormone-sensitive conditions.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109148"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828223","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":"Subtle morphological and molecular responses to low-dose diethylstilbestrol in the developing rat penis","authors":"Emilie Elmelund,&nbsp;Marie Berg,&nbsp;Mikael Pedersen,&nbsp;Terje Svingen,&nbsp;Monica K. Draskau","doi":"10.1016/j.reprotox.2025.109149","DOIUrl":"10.1016/j.reprotox.2025.109149","url":null,"abstract":"<div><div>Developmental exposure to estrogenic chemicals can cause hypospadias in mice. In rats and humans this link is less well-defined, and the causal relationship remains unclear. This likely pertains to uncertainties regarding direct and indirect effects of estrogens in the genital tubercle (GT) and inconsistent evaluations of potentially mild disruptions, especially in rats. In this study, we investigated the effects of late gestational exposure to the estrogenic chemical diethylstilbestrol (DES) in low doses on male rat penis differentiation. In an <em>ex vivo</em> GT culture system, DES caused subtle changes to GT morphology after 96 h in culture, but with no overt phenotype. Moreover, DES upregulated <em>Ar</em> and AR<em>-</em>responsive genes in the GT. When exposing rats <em>in vivo</em> from gestational day (GD) 7–21, DES did not cause genital malformations in the fetal males, but we observed slight abnormalities to GT morphology in µCT scans. Our study indicates that DES may directly modulate hormone signaling in the GT during fetal masculinization.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109149"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834649","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":"BDE-47 has cytotoxicity on human sperm by inducing apoptosis, mitochondrial dysfunction, and membrane damage","authors":"Guoliang Zhou ,&nbsp;Wenbo Zhang ,&nbsp;Hao Wang ,&nbsp;Tao Luo ,&nbsp;Yuan Yang","doi":"10.1016/j.reprotox.2026.109171","DOIUrl":"10.1016/j.reprotox.2026.109171","url":null,"abstract":"<div><div>Persistent organic pollutants, including 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), pose significant threats to human health, with growing evidence linking their exposure to male reproductive toxicity. However, research directly addressing BDE-47 toxicity in ejaculated human sperm and integrating functional sperm endpoints, mechanistic markers, and in silico network toxicology remains limited. This study investigated the toxic effects of BDE-47 on human sperm <em>in vitro</em>. Exposure to BDE-47 (25, 50, 75, and 100 μM) impaired multiple sperm functional endpoints, including viability, total and progressive motility, and penetration into methylcellulose; BDE-47 also reduced computer-aided sperm analysis (CASA)-derived kinematic parameters in motile spermatozoa. Penetration into the methylcellulose medium was the most sensitive endpoint, being reduced at all concentrations, whereas decreases in viability and motility became evident only at higher concentrations. Moreover, BDE-47 induced mitochondrial dysfunction, as reflected by decreased mitochondrial membrane potential (MMP), and was accompanied by reduced total ATP levels. Additionally, BDE-47 increased malondialdehyde (MDA) levels, consistent with plasma membrane damage. Apoptosis-associated changes were observed, including loss of plasma membrane integrity and increased nuclear DNA fragmentation, accompanied by a pro-apoptotic shift in protein levels (increased Bax and decreased Bcl-2 protein levels). Network toxicology analysis further indicated biological processes related to apoptosis and cell death, along with mitochondrial dysfunction involved in BDE-47-induced toxicity. Collectively, these findings suggest that BDE-47 induces sperm toxicity through mitochondrial dysfunction, membrane damage, and apoptosis, leading to impaired function and viability. This study therefore extends previous PBDE studies in animals and cell models by providing direct evidence in ejaculated human sperm.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109171"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041517","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}