Reproductive toxicology最新文献

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Blocking T-type calcium channels disrupts spermatogenesis in vivo and adversely affects spermatocytes in vitro by impairing mitochondrial function and autophagic flux 阻断t型钙通道会破坏体内精子发生,并通过损害线粒体功能和自噬通量对体外精母细胞产生不利影响。
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-09-08 DOI: 10.1016/j.reprotox.2025.109048
Xiuling Zhao , Lei Wang , Shiqin Huang , Lin Liu , Xiaorong Wang , Liping Pu , Hao Chen , Junyu Nie
{"title":"Blocking T-type calcium channels disrupts spermatogenesis in vivo and adversely affects spermatocytes in vitro by impairing mitochondrial function and autophagic flux","authors":"Xiuling Zhao ,&nbsp;Lei Wang ,&nbsp;Shiqin Huang ,&nbsp;Lin Liu ,&nbsp;Xiaorong Wang ,&nbsp;Liping Pu ,&nbsp;Hao Chen ,&nbsp;Junyu Nie","doi":"10.1016/j.reprotox.2025.109048","DOIUrl":"10.1016/j.reprotox.2025.109048","url":null,"abstract":"<div><div>T-type calcium channels are pivotal in spermatogenesis. To evaluate the molecular mechanisms by which T-type calcium channels regulate spermatogenesis, we constructed animal and cellular models using T-type calcium channel inhibitor flunarizine (FNZ). Intraperitoneal administration of FNZ (30 mg/kg) significantly impaired sperm motility, inhibited testicular germ cell proliferation, and disrupted sperm mitochondrial function in male mice. FNZ, at concentrations of 7.5 μM, 15 μM, and 30 μM, significantly inhibited mouse spermatocyte (GC-2) cells proliferation. The detrimental effects of FNZ were mediated through the disruption of calcium homeostasis, mitochondrial dysfunction, and the induction of apoptosis. Moreover, FNZ exposure resulted in the accumulation of autophagosomes and an upregulation of P62 protein, which is implicated in autophagic degradation. Notably, the autophagy activator Rapamycin (Rapa) was found to mitigate FNZ-induced cellular damage in GC-2 cells by enhancing autophagy process. Conversely, chloroquine (CQ), an autophagy inhibitor that disrupts lysosomal degradation, corroborated the role of FNZ in autophagy modulation. Our results indicate that FNZ induces mitochondrial damage, impairs sperm motility and spermatocyte proliferation, and is accompanied by obstacles to autophagic flux.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109048"},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034063","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}
引用次数: 0
Protective effect of ginsenoside Rg3 on DBP-induced spermatogenesis injury via the Src/PI3K signaling pathway 人参皂苷Rg3通过Src/PI3K信号通路对dbp诱导的精子发生损伤的保护作用
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-09-08 DOI: 10.1016/j.reprotox.2025.109047
Huan Li , Hongyan Wang , Xiaolei Xu, Li Qu, Xiuling Sun, Jing Zhang
{"title":"Protective effect of ginsenoside Rg3 on DBP-induced spermatogenesis injury via the Src/PI3K signaling pathway","authors":"Huan Li ,&nbsp;Hongyan Wang ,&nbsp;Xiaolei Xu,&nbsp;Li Qu,&nbsp;Xiuling Sun,&nbsp;Jing Zhang","doi":"10.1016/j.reprotox.2025.109047","DOIUrl":"10.1016/j.reprotox.2025.109047","url":null,"abstract":"<div><div>This study aimed to investigate the protective mechanism of Ginsenoside Rg3 (Rg3) against Di-n-butyl phthalate (DBP) induced spermatogenic damage, focusing on the Src/PI3K/Akt pathway. In vivo experiments demonstrated that Rg3 restored DBP-induced dysregulation of gap junction (GJ) protein connexin 43 (Cx43), improved testicular structure, enhanced sperm parameters (count and motility), and upregulated phosphorylation of Src, PI3K, and Akt (p-Src, p-PI3K, p-Akt) in mice. In vitro studies, using the metabolite of DBP, monobutyl phthalate (MBP), and pathway inhibitors (PP2 for Src and LY294002 for PI3K), further confirmed these effects. Rg3 increased antioxidant enzyme activity, reduced oxidative stress marker MDA, and enhanced the expression of p-Src, p-PI3K, p-Akt, and Cx43 in MBP-treated TM4 Sertoli cells. Inhibitor experiments confirmed that the Src/PI3K pathway mediates Rg3’s protective action. These findings suggest that Rg3 alleviates DBP/MBP-induced male reproductive dysfunction by enhancing antioxidant capacity and reactivating the Src/PI3K/Akt signaling pathway, which helps restore blood-testis barrier (BTB) integrity through Cx43 stabilization. Thus, Rg3 may serve as a potential therapeutic agent for environmental toxicant-related male infertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109047"},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034102","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}
引用次数: 0
The effects of imidacloprid exposure on the mouse ovary in vivo 吡虫啉对小鼠卵巢的体内影响。
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-09-04 DOI: 10.1016/j.reprotox.2025.109045
Vasiliki E. Mourikes, Colin Lee, Jadesola I. Oladosu, Ashley Deviney, Winter Stubblefield, Mary J. Laws, Megan Mahoney, Jodi A. Flaws
{"title":"The effects of imidacloprid exposure on the mouse ovary in vivo","authors":"Vasiliki E. Mourikes,&nbsp;Colin Lee,&nbsp;Jadesola I. Oladosu,&nbsp;Ashley Deviney,&nbsp;Winter Stubblefield,&nbsp;Mary J. Laws,&nbsp;Megan Mahoney,&nbsp;Jodi A. Flaws","doi":"10.1016/j.reprotox.2025.109045","DOIUrl":"10.1016/j.reprotox.2025.109045","url":null,"abstract":"<div><div>Imidacloprid (IMI) is an insect-selective synthetic nicotine derivative used in commercial agricultural systems, home gardening, and veterinary pharmaceuticals. People are exposed to IMI through consumption of contaminated food and water and through contact with companion animals. However, the effects of IMI on the female reproductive system are not well understood. Thus, we tested the hypothesis that IMI reaches the ovaries and adversely affects the female reproductive system. Adult female mice were orally exposed to vehicle control (dimethyl sulfoxide) or IMI for 30 days. Estrous cyclicity was monitored for the last 14 days of the dosing period and mice were euthanized in diestrus. Sera were collected for gonadotropin and sex steroid hormone quantification. Ovaries were collected for IMI and IMI metabolite quantification, and to assess follicle numbers and gene expression. IMI and metabolites were significantly higher in exposed mice compared to controls. Further, IMI decreased the number of healthy ovarian follicles and increased the ovarian expression of the enzymes <em>Cyp2e1</em> and <em>Cyp19a1</em> compared to control. IMI also increased circulating luteinizing hormone levels (LH), but did not affect circulating follicle-stimulating hormone levels or sex steroid hormone levels compared to control. IMI did not affect body weight, ovarian weight, or estrous cyclicity compared to control. Collectively, these data indicate that IMI reaches the ovaries and affects some female reproductive outcomes such as ovarian follicle numbers, LH levels, and ovarian expression of enzymes.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109045"},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008461","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}
引用次数: 0
Caffeic acid phenethyl ester disrupts germ layer specification in Xenopus embryos 咖啡酸苯乙酯对爪蟾胚胎胚层发育的影响
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-09-04 DOI: 10.1016/j.reprotox.2025.109046
Gang-Ho Yoon, Myeoung Su Kim, Sun-Cheol Choi
{"title":"Caffeic acid phenethyl ester disrupts germ layer specification in Xenopus embryos","authors":"Gang-Ho Yoon,&nbsp;Myeoung Su Kim,&nbsp;Sun-Cheol Choi","doi":"10.1016/j.reprotox.2025.109046","DOIUrl":"10.1016/j.reprotox.2025.109046","url":null,"abstract":"<div><div><em>Xenopus</em> embryo serves as an ideal model for teratogenesis assays to observe the effects of any compounds on the cellular processes crucial for early development and adult tissue homeostasis. In our screening of a chemical library with frog embryo, caffeic acid phenethyl ester (CAPE) was found to upregulate the FGF/MAPK pathway, disrupting germ layer formation in early development. Exposure to CAPE interfered with the formation of anterior-posterior body axis and of ectodermal derivatives such as eyes, dorsal fin and pigment cells. These inhibitory effects were achieved by promoting paraxial mesodermal specification and neural differentiation concomitant with a repression of epidermal and neural crest cell fates. This compound also induced the caudalization of anterior neural fate, thereby recapitulating the activity of the FGF/MAPK signals in the anterior-posterior patterning of neural tissue. Consistently, phosphorylation of extracellular signal-regulated kinase (ERK) was elevated in CAPE-treated cells, which was mediated by the FGFR1 and FGFR4 pathway. Together, these results suggest that CAPE functions as an activator of the FGF/MAPK signaling pathway, generating severe teratogenic effects on germ layer specification in vertebrate early development.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109046"},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996567","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}
引用次数: 0
Positioning nutrigenomics and nutrigenetics within the framework of male infertility exploration 营养基因组学和营养遗传学在男性不育症研究框架中的定位。
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-09-02 DOI: 10.1016/j.reprotox.2025.109043
Emmanuel Osei Nkansah, Binbin Xu, Yunzhu Lan, Mohammad Ishraq Zafar
{"title":"Positioning nutrigenomics and nutrigenetics within the framework of male infertility exploration","authors":"Emmanuel Osei Nkansah,&nbsp;Binbin Xu,&nbsp;Yunzhu Lan,&nbsp;Mohammad Ishraq Zafar","doi":"10.1016/j.reprotox.2025.109043","DOIUrl":"10.1016/j.reprotox.2025.109043","url":null,"abstract":"<div><div>Male infertility, a complex result of genetic, environmental, and lifestyle factors, has gained significant focus in contemporary medical research. The intricate interplay between genetics, nutrition, and male fertility is crucial for understanding the complex mechanisms that underlie male reproductive health. The twenty-first century has seen a paradigm shift in medicine, where holistic personalized medical care is posited to be ideal and effective. In this regard, this narrative review explored how the convergence of dietary habits and genetic predispositions influence male fertility in the context of predictive, preventive, and personalized medicine. This review explored the evolving landscape of genetic insights into male infertility, creating awareness of their possible engagement as genetic predictors for idiopathic male infertility. It also dissects the roles of nutrigenomics and nutrigenetics in shaping preventive male reproductive medicine strategies through distinguishing the influence of dietary components on genetic expression and further elucidating how epigenetic alterations, influenced by dietary components, impact male fertility, potentially imparting transgenerational effects. Furthermore, this review offers potential personalized reproductive remedies in the form of functional and super foods, gut microbiome enhancers, redox homeostasis and proposes personalized nutrition as an intervention with high prospects in the context of improving male fertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109043"},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001455","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}
引用次数: 0
Association of urinary phthalate metabolites and polycystic ovary syndrome in women undergoing in vitro fertilization 体外受精妇女尿邻苯二甲酸酯代谢物与多囊卵巢综合征的关系。
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-09-01 DOI: 10.1016/j.reprotox.2025.109041
Wenjie Zhou , Shuifang Lei , Hong Lv , Yangqian Jiang , Tianyu Sun , Yanjie Zhang , Hongxia Ma , Jie Wu , Yuan Lin
{"title":"Association of urinary phthalate metabolites and polycystic ovary syndrome in women undergoing in vitro fertilization","authors":"Wenjie Zhou ,&nbsp;Shuifang Lei ,&nbsp;Hong Lv ,&nbsp;Yangqian Jiang ,&nbsp;Tianyu Sun ,&nbsp;Yanjie Zhang ,&nbsp;Hongxia Ma ,&nbsp;Jie Wu ,&nbsp;Yuan Lin","doi":"10.1016/j.reprotox.2025.109041","DOIUrl":"10.1016/j.reprotox.2025.109041","url":null,"abstract":"<div><h3>Background/objectives</h3><div>Phthalates are a group of ubiquitous environmental endocrine disruptors that can be detected in human body and exert adverse effects on reproductive health. We aimed to explore the correlation of phthalate exposure with polycystic ovary syndrome (PCOS).</div></div><div><h3>Methods</h3><div>We included 420 females who underwent assisted reproductive technology (ART) treatments between 2015 and 2018 in Jiangsu, China, comprising 94 PCOS cases and 326 controls. Seventeen phthalate metabolites and three metabolites of phthalate substitutes were measured in the urine before the ART treatment. Multiple logistic and linear regression models were performed to assess the relationships of phthalate exposure with PCOS and sex hormone levels, including luteinizing hormone (LH), estradiol (E<sub>2</sub>), follicle-stimulating hormone (FSH), and mediation analysis was conducted to assess the mediating effect of sex hormones. Potential covariates in the regression models include age, area of residence, household income, education, body mass index (BMI), tobacco use and alcohol intake.</div></div><div><h3>Results</h3><div>We found that the concentration of di (2-ethylhexyl) phthalate (ΣDEHP) (aOR = 1.40, 95 % CI: 1.02–1.92, <em>P</em> = 0.039) was associated with higher odds of PCOS. Additionally, increased levels of ΣDEHP (β = 0.08, 95 % CI: 0.01–0.15, <em>P</em> = 0.021) and its metabolites were correlated with elevated LH concentrations. In the mediation analysis, elevated LH mediated 34.56 % of the association between ΣDEHP and PCOS, respectively.</div></div><div><h3>Conclusion</h3><div>Exposure to environmental levels of DEHP was associated with increased odds of PCOS, partially mediated by elevated LH levels.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109041"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993378","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}
引用次数: 0
Fluvastatin mitigates the testicular toxicity of Azathioprine via regulating mTOR pathway and restoring autophagy/apoptosis balance 氟伐他汀通过调节mTOR通路和恢复自噬/凋亡平衡来减轻硫唑嘌呤的睾丸毒性
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-08-30 DOI: 10.1016/j.reprotox.2025.109042
Samar Sakr , Nahla M. Ibrahim , Basma A. Ibrahim , Ansam M. Z. El Desoky , Bassant T. Abd Elbaki , Mamdouh Eldesoqui , Zeinab A. Mohammed
{"title":"Fluvastatin mitigates the testicular toxicity of Azathioprine via regulating mTOR pathway and restoring autophagy/apoptosis balance","authors":"Samar Sakr ,&nbsp;Nahla M. Ibrahim ,&nbsp;Basma A. Ibrahim ,&nbsp;Ansam M. Z. El Desoky ,&nbsp;Bassant T. Abd Elbaki ,&nbsp;Mamdouh Eldesoqui ,&nbsp;Zeinab A. Mohammed","doi":"10.1016/j.reprotox.2025.109042","DOIUrl":"10.1016/j.reprotox.2025.109042","url":null,"abstract":"<div><div>Azathioprine (AZA) is a widely employed immunosuppressive and chemotherapeutic medication that may exhibit detrimental effects on testes. Fluvastatin is a lipid-lowering agent with promising reproductive properties. This work aimed to assess the testicular toxicity of AZA and the probable protective role of fluvastatin. Forty adult male albino rats were assigned to four equal groups: Control, Fluvastatin (6 mg/kg), AZA (15 mg/kg), and AZA and fluvastatin. After 4 weeks, sera were obtained for testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) investigations. Semen samples were collected to test sperm parameters. Testes were harvested for biochemical investigations, gene transcription, and histological and immunohistochemical examinations. In the AZA group, results exposed a considerable decline in sperm parameters, sex hormones, and testicular weight. Oxidative stress was evident by the diminished catalase (CAT) and superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels elevation. Inflammation was reflected by increased NOD-Like Receptor family Pyrin domain-containing 3 inflammasome (NLRP3), Interleukin-6 (IL-6), and Interleukin-1 Beta (IL-1β), besides decreased Interleukin-10 (IL-10). Gene transcription indicated that AZA disrupts the mammalian target of the rapamycin (mTOR) cascade and the autophagic and apoptotic-related genes in testes, thus impairing the blood-testis barrier (BTB) and spermatogenesis. Testes displayed disorganized germinal epithelium and deformed seminiferous tubules. A positive p53 immunoreaction and a lost vimentin spoke-like pattern were also demonstrated. Fluvastatin exhibited antioxidant and anti-inflammatory defense, regulated the mTOR pathway, restored the lost autophagy/apoptosis balance, and improved the architectural and immunohistochemical alterations. Therefore, fluvastatin can be considered a candidate for future usage to combat AZA-induced testicular toxicity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109042"},"PeriodicalIF":2.8,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925165","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}
引用次数: 0
New approach methodologies for assessing developmental toxicity of pharmaceuticals: Case examples and future directions 评估药物发育毒性的新方法方法:案例和未来方向。
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-08-28 DOI: 10.1016/j.reprotox.2025.109035
Nicola Powles-Glover , Allen R. Kaczor , Steven Van Cruchten , Christopher J. Bowman , Kimberly C. Brannen , Claudia Demarta-Gatsi , Isabelle LeConte , Amer Jamalpoor , Fumito Mikashima , Shermaine Mitchell-Ryan , Dinesh Stanislaus , Peter Theunissen , Belen Tornesi , Ronald L. Wange , Connie L. Chen
{"title":"New approach methodologies for assessing developmental toxicity of pharmaceuticals: Case examples and future directions","authors":"Nicola Powles-Glover ,&nbsp;Allen R. Kaczor ,&nbsp;Steven Van Cruchten ,&nbsp;Christopher J. Bowman ,&nbsp;Kimberly C. Brannen ,&nbsp;Claudia Demarta-Gatsi ,&nbsp;Isabelle LeConte ,&nbsp;Amer Jamalpoor ,&nbsp;Fumito Mikashima ,&nbsp;Shermaine Mitchell-Ryan ,&nbsp;Dinesh Stanislaus ,&nbsp;Peter Theunissen ,&nbsp;Belen Tornesi ,&nbsp;Ronald L. Wange ,&nbsp;Connie L. Chen","doi":"10.1016/j.reprotox.2025.109035","DOIUrl":"10.1016/j.reprotox.2025.109035","url":null,"abstract":"<div><div>Several new approach methodologies (NAMs) for developmental toxicity (Dev Tox) testing are being used by pharmaceutical companies for derisking or for exploring Dev Tox mechanisms. Regulatory adoption of these NAMs-based approaches as being adequate for Dev Tox risk assessment has been more challenging, due, in part, to dynamic changes in the conceptus and placenta throughout development and the impact of the pharmaceutical on the mother’s physiology, which may also have an embryo-fetal impact. Still, there is currently a recognition by Health Authorities that there are certain contexts-of-use under which Dev Tox NAMs can provide information that is adequate to inform risk. This has been adopted in the 3rd revision of the ICH S5 guideline, which provides a path to qualify Dev Tox NAMs for regulatory decision making. Despite this opportunity, pharmaceutical companies rarely submit Dev Tox NAMs to Health Authorities for qualification or with intent to support regulatory decision making. This may be in part due to the need for a greater understanding of the biological relationship between currently available Dev Tox NAMs and in vivo outcome, applicability domain, translatability, predictivity, and that these NAMs do not cover the complete scope of embryo-fetal development. Furthermore, there is a lack of Dev Tox NAMs data visibility to Health Authorities. To use Dev Tox NAMs for regulatory decision making, more data sharing with Health Authorities and further understanding the applicability domain of these methodologies are needed.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109035"},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966862","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}
引用次数: 0
Chikusetsusaponin IVa ameliorates paroxetine-induced Leydig cells (TM3 cells) injury via the Nrf2/HO-1 signaling pathway Chikusetsusaponin IVa通过Nrf2/HO-1信号通路改善帕罗西汀诱导的间质细胞(TM3细胞)损伤
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-08-28 DOI: 10.1016/j.reprotox.2025.109039
Qianqian Huang , Haiying Wu , Xiangxin Xiao , Zhen Lu , Xiuping Fan , Wenhong Cao , Suqing Liu , Xiaoming Qin
{"title":"Chikusetsusaponin IVa ameliorates paroxetine-induced Leydig cells (TM3 cells) injury via the Nrf2/HO-1 signaling pathway","authors":"Qianqian Huang ,&nbsp;Haiying Wu ,&nbsp;Xiangxin Xiao ,&nbsp;Zhen Lu ,&nbsp;Xiuping Fan ,&nbsp;Wenhong Cao ,&nbsp;Suqing Liu ,&nbsp;Xiaoming Qin","doi":"10.1016/j.reprotox.2025.109039","DOIUrl":"10.1016/j.reprotox.2025.109039","url":null,"abstract":"<div><div>Paroxetine (PRX) exhibits significant toxic effects on the male reproductive system. Previous animal studies have demonstrated that <em>Pfaffia glomerata</em> extract can ameliorate PRX-induced sexual dysfunction in male mice, but its active components and underlying mechanisms remain unclear. Chikusetsusaponin IVa (CHS-IVa), a major saponin component of <em>Pfaffia glomerata</em> with well-documented antioxidant and anti-apoptotic activities, has become a research focus. This study aimed to investigate whether CHS-IVa could mitigate PRX-induced injury in mouse Leydig cells (TM3 cells) by regulating oxidative stress, apoptosis, and androgen synthesis pathways. To achieve this, a PRX-induced injury model in TM3 cells was established and subjected to comprehensive evaluation using CCK-8 assay for cell viability, ELISA for sex hormone levels, DCFH-DA fluorescent probe for reactive oxygen species (ROS) detection, and RT-qPCR/Western blot for mRNA and protein expression analysis. Results showed that compared to PRX group, CHS-IVa (6.25 μg/mL) significantly increased cell viability by 12.9 % (<em>p</em> &lt; 0.05); activated Nrf2/HO1 signaling pathway, reducing intracellular ROS levels by at least 21.9 % (<em>p</em> &lt; 0.05), thereby alleviating oxidative stress injury; upregulated mRNA expression of androgen synthesis-related genes (StAR, CYP11a1, CYP17a1, LHr) by over 2-fold (<em>p</em> &lt; 0.05), with maximal increases in testosterone, dihydrotestosterone and luteinizing hormone levels by 8.4 %, 50.4 % and 13.0 % respectively (<em>p</em> &lt; 0.05); enhanced anti-apoptotic factor Bcl-2 mRNA and protein expression by up to 3.4-fold and 1.6-fold (<em>p</em> &lt; 0.05), while reducing pro-apoptotic factor Bax mRNA and protein expression by 40.5 % and 44.6 % (<em>p</em> &lt; 0.05), and decreasing Caspase-3 mRNA expression by 61.5 % (<em>p</em> &lt; 0.05), ultimately reducing PRX-induced abnormal apoptosis in TM3 cells. In conclusion, CHS-IVa serves as the key active component in <em>Pfaffia glomerata</em> that protects against PRX-induced reproductive toxicity by ameliorating injury in TM3 cells through multiple mechanisms.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109039"},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916715","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}
引用次数: 0
Abamectin disrupts sperm function through the alteration of PKA activity and tyrosine phosphorylation in boar spermatozoa 阿维菌素通过改变猪精子中的PKA活性和酪氨酸磷酸化来破坏精子功能
IF 2.8 4区 医学
Reproductive toxicology Pub Date : 2025-08-27 DOI: 10.1016/j.reprotox.2025.109040
Claudine Uwamahoro , Jae-Hwan Jo , Seung-Ik Jang , Eun-Ju Jung , Woo-Jin Lee , Jeong-Won Bae , Daehyun Kim , Junkoo Yi , Sangsu Shin , Joonho Moon , Woo-Sung Kwon
{"title":"Abamectin disrupts sperm function through the alteration of PKA activity and tyrosine phosphorylation in boar spermatozoa","authors":"Claudine Uwamahoro ,&nbsp;Jae-Hwan Jo ,&nbsp;Seung-Ik Jang ,&nbsp;Eun-Ju Jung ,&nbsp;Woo-Jin Lee ,&nbsp;Jeong-Won Bae ,&nbsp;Daehyun Kim ,&nbsp;Junkoo Yi ,&nbsp;Sangsu Shin ,&nbsp;Joonho Moon ,&nbsp;Woo-Sung Kwon","doi":"10.1016/j.reprotox.2025.109040","DOIUrl":"10.1016/j.reprotox.2025.109040","url":null,"abstract":"<div><div>The potential toxicity of abamectin (ABM), a macrocyclic lactone insecticide widely used in agriculture, in non-target organisms has raised concerns. Therefore, this study aimed to investigate the effects of ABM on sperm function, focusing on motility, kinematics, ATP levels, viability, protein kinase A (PKA) activity, and tyrosine phosphorylation. Boar spermatozoa were incubated with various ABM concentrations (0, 1, 5, 10, 15, 25, 50, and 100 µM) under capacitating conditions and assessed through computer-assisted sperm analysis, Hoechst 33258/chlortetracycline staining, ATP and viability assays, and Western blotting. The results revealed a dose-dependent decline in sperm motility and ATP levels starting at 10 µM. Sperm capacitation was significantly altered at concentrations of at least 25 µM, with an increase in capacitated spermatozoa and a decrease in non-capacitated spermatozoa. However, overall cell viability remained unaffected. Western blot analysis showed abnormal alterations in PKA substrates and tyrosine-phosphorylated proteins. These findings suggest ABM disrupts sperm function and key fertilization pathways, indicating potential risks to male fertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109040"},"PeriodicalIF":2.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925166","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}
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