Reproductive toxicology最新文献_第2页

Atrazine and diazinon inhibit oocyte maturation and ovulation in zebrafish 阿特拉津和二嗪醌抑制斑马鱼卵母细胞成熟和排卵。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-22 DOI: 10.1016/j.reprotox.2026.109172

Md Hasan Ali , Maisum Sarwar Jyoti , Mrityunjoy Acharjee , Shakhawat Hossain , Saokat Ahamed , Md. Forhad Hossain , Toshinobu Tokumoto

Oocyte maturation and ovulation are well characterized biological processes in fish that are induced by progestins through the coordination of nongenomic actions via the membrane progesterone receptor (mPR) and genomic actions via the nuclear progesterone receptor (Pgr). In zebrafish, the effects of chemicals on these processes can be elucidated using in vitro and in vivo oocyte maturation and ovulation assays. The binding affinity of chemicals for mPR and Pgr can be analyzed using a recently established graphene quantum dot (GQD)-labeled mPR and Pgr binding assay. Combining these physiological and biochemical analyses makes it possible to investigate whether the effects of chemical substances on oocyte maturation and ovulation are mediated by mPR and Pgr. In this study, the effects of herbicides and pesticides on fish oocyte maturation and ovulation were evaluated using in vitro and in vivo assays. The findings revealed that at concentrations greater than 0.1 μM, atrazine (ATZ) and diazinon (DZN) substantially reduced oocyte maturation, whereas 2,4-D exposure did not have a similar effect. ATZ and DZN reduced oocyte maturation and ovulation in vivo. However, the concentrations of these compounds required to inhibit ovulation were significantly lower than those required to inhibit oocyte maturation. The binding affinity of endocrine-disrupting chemicals (EDCs) was analyzed using GQD-labeled mPR and Pgr binding assays. All three EDCs—ATZ, DZN, and 2,4-D—exhibited binding affinity for mPR. For Pgr, DZN and 2,4-D exhibited binding affinity, but ATZ did not. These results suggest that ATZ and DZN prevent fish oocyte maturation and ovulation by binding to mPR.

卵母细胞成熟和排卵是由孕激素通过膜孕激素受体（mPR）和核孕激素受体（Pgr）的非基因组作用协调诱导的鱼类生物过程。在斑马鱼中，化学物质对这些过程的影响可以通过体外和体内卵母细胞成熟和排卵试验来阐明。化学物质对mPR和Pgr的结合亲和力可以使用最近建立的石墨烯量子点（GQD）标记的mPR和Pgr结合实验来分析。结合这些生理生化分析，可以探讨化学物质对卵母细胞成熟和排卵的影响是否由mPR和Pgr介导。本研究通过体外和体内实验，评价了除草剂和农药对鱼类卵母细胞成熟和排卵的影响。结果表明，在浓度大于0.1μM时，阿特拉津（ATZ）和二嗪醌（DZN）显著降低卵母细胞成熟，而2,4- d暴露没有类似的影响。ATZ和DZN在体内降低卵母细胞成熟和排卵。然而，抑制排卵所需的这些化合物的浓度明显低于抑制卵母细胞成熟所需的浓度。使用gqd标记的mPR和Pgr结合试验分析内分泌干扰化学物质（EDCs）的结合亲和力。所有三种EDCs-ATZ、DZN和2,4- d都表现出与mPR的结合亲和力。对于Pgr， DZN和2,4- d具有结合亲和力，而ATZ没有。这些结果表明，ATZ和DZN通过与mPR结合来阻止鱼卵母细胞成熟和排卵。

{"title":"Atrazine and diazinon inhibit oocyte maturation and ovulation in zebrafish","authors":"Md Hasan Ali , Maisum Sarwar Jyoti , Mrityunjoy Acharjee , Shakhawat Hossain , Saokat Ahamed , Md. Forhad Hossain , Toshinobu Tokumoto","doi":"10.1016/j.reprotox.2026.109172","DOIUrl":"10.1016/j.reprotox.2026.109172","url":null,"abstract":"<div><div>Oocyte maturation and ovulation are well characterized biological processes in fish that are induced by progestins through the coordination of nongenomic actions via the membrane progesterone receptor (mPR) and genomic actions via the nuclear progesterone receptor (Pgr). In zebrafish, the effects of chemicals on these processes can be elucidated using <em>in vitro</em> and <em>in vivo</em> oocyte maturation and ovulation assays. The binding affinity of chemicals for mPR and Pgr can be analyzed using a recently established graphene quantum dot (GQD)-labeled mPR and Pgr binding assay. Combining these physiological and biochemical analyses makes it possible to investigate whether the effects of chemical substances on oocyte maturation and ovulation are mediated by mPR and Pgr. In this study, the effects of herbicides and pesticides on fish oocyte maturation and ovulation were evaluated using <em>in vitro</em> and <em>in vivo</em> assays. The findings revealed that at concentrations greater than 0.1 μM, atrazine (ATZ) and diazinon (DZN) substantially reduced oocyte maturation, whereas 2,4-D exposure did not have a similar effect. ATZ and DZN reduced oocyte maturation and ovulation <em>in vivo</em>. However, the concentrations of these compounds required to inhibit ovulation were significantly lower than those required to inhibit oocyte maturation. The binding affinity of endocrine-disrupting chemicals (EDCs) was analyzed using GQD-labeled mPR and Pgr binding assays. All three EDCs—ATZ, DZN, and 2,4-D—exhibited binding affinity for mPR. For Pgr, DZN and 2,4-D exhibited binding affinity, but ATZ did not. These results suggest that ATZ and DZN prevent fish oocyte maturation and ovulation by binding to mPR.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109172"},"PeriodicalIF":2.8,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041566","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

BDE-47 has cytotoxicity on human sperm by inducing apoptosis, mitochondrial dysfunction, and membrane damage BDE-47通过诱导细胞凋亡、线粒体功能障碍和膜损伤对人类精子具有细胞毒性。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-21 DOI: 10.1016/j.reprotox.2026.109171

Guoliang Zhou , Wenbo Zhang , Hao Wang , Tao Luo , Yuan Yang

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 in vitro. 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.

持久性有机污染物，包括2,2',4,4'-四溴联苯醚（BDE-47），对人类健康构成重大威胁，越来越多的证据表明，接触这些污染物与男性生殖毒性有关。然而，直接研究BDE-47对人类射精精子的毒性，并整合功能性精子端点、机制标记和硅网络毒理学的研究仍然有限。本研究探讨了BDE-47对体外人精子的毒性作用。暴露于BDE-47（25、50、75和100μM）会损害多个精子的功能终点，包括活力、总运动和渐进运动，以及对甲基纤维素的渗透；BDE-47还降低了计算机辅助精子分析（CASA）得出的运动精子的运动学参数。对甲基纤维素介质的渗透是最敏感的终点，在所有浓度下都被降低，而活力和运动性的降低只有在较高浓度下才明显。此外，BDE-47诱导线粒体功能障碍，表现为线粒体膜电位（MMP）下降，并伴有总ATP水平降低。此外，BDE-47增加丙二醛（MDA）水平，与质膜损伤一致。观察到凋亡相关的变化，包括质膜完整性的丧失和核DNA断裂的增加，伴随着蛋白水平的促凋亡变化（Bax增加，Bcl-2蛋白水平降低）。网络毒理学分析进一步表明，与凋亡和细胞死亡相关的生物学过程以及线粒体功能障碍参与了bde -47诱导的毒性。总之，这些发现表明BDE-47通过线粒体功能障碍、膜损伤和细胞凋亡诱导精子毒性，导致精子功能和活力受损。因此，这项研究通过提供人类射精精子的直接证据，扩展了先前在动物和细胞模型中进行的多溴二苯醚研究。

{"title":"BDE-47 has cytotoxicity on human sperm by inducing apoptosis, mitochondrial dysfunction, and membrane damage","authors":"Guoliang Zhou , Wenbo Zhang , Hao Wang , Tao Luo , 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":"2026-01-21","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}

引用次数: 0

Effects of perfluorooctane sulfonate (PFOS) and tetrabromobisphenol A (TBBPA) on reproductive development in rats 全氟辛烷磺酸和四溴双酚A对大鼠生殖发育的影响。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-16 DOI: 10.1016/j.reprotox.2026.109170

Mette Stub, Louise Ramhøj, Marta Axelstad, Mikael Pedersen, Terje Svingen

Perfluorooctane sulfonate (PFOS) and tetrabromobisphenol A (TBBPA) are environmental pollutants with known endocrine disrupting potential. Both substances display various thyroid hormone (TH) system disrupting effects, both in vitro and in vivo, but effects on the reproductive system following developmental exposure are less characterized. Recently, we described effects following perinatal exposure to PFOS (0.4 or 0.8 mg/kg bw/day) and TBBPA (250 or 500 mg/kg bw/day) on the TH system in rats, showing a complex effect pattern. Here, we report data on reproductive endpoints (anogenital distance (AGD), nipple retention (NR) and male reproductive organ weights) and steroid hormone levels in offspring from the same in vivo study. Results indicate that PFOS and TBBPA do not affect antiandrogenic endpoints such as AGD and NR at administered doses. PFOS had a modest effect on steroidogenesis, increasing estrone levels in fetuses, and in the 16-day-old pups increasing corticosterone levels in the low-dose group and progesterone levels in both dose groups, along with a small reduction in adjusted testes weight. TBBPA did not alter steroid hormone levels at the fetal stage, but hormones were disrupted in the 16-day-old pups. Here TBBPA increased progesterone levels in low-dose and testosterone levels in high-dose pups and reduced estrone levels in high-dose group to values below the limit of quantification (LOQ). These findings suggest that PFOS and TBBPA have some effects on circulating steroid hormone levels, but minimal effects on androgen-sensitive endpoints in rats.

全氟辛烷磺酸（PFOS）和四溴双酚A （TBBPA）是已知具有内分泌干扰潜力的环境污染物。这两种物质在体内和体外都表现出不同的甲状腺激素（TH）系统干扰作用，但对发育暴露后生殖系统的影响较少。最近，我们描述了围产期暴露于PFOS（0.4或0.8mg/kg bw/day）和TBBPA（250或500mg/kg bw/day）对大鼠TH系统的影响，显示出复杂的影响模式。在这里，我们报告了来自同一体内研究的后代生殖终点（肛门生殖器距离（AGD），乳头保留（NR）和雄性生殖器官重量）和类固醇激素水平的数据。结果表明，在给药剂量下，PFOS和TBBPA不影响抗雄激素终点，如AGD和NR。全氟辛烷磺酸对类固醇生成有适度的影响，增加了胎儿的雌激素水平，在16日龄的幼崽中，低剂量组的皮质酮水平和两个剂量组的孕酮水平都有所增加，同时调整后的睾丸重量也有小幅下降。TBBPA没有改变胎儿阶段的类固醇激素水平，但在16天大的幼崽中激素被破坏。在这里，TBBPA增加了低剂量幼犬的孕酮水平和高剂量幼犬的睾酮水平，并将高剂量组的雌酮水平降低到定量限（LOQ）以下。这些发现表明，全氟辛烷磺酸和TBBPA对循环类固醇激素水平有一定影响，但对大鼠雄激素敏感终点的影响很小。

{"title":"Effects of perfluorooctane sulfonate (PFOS) and tetrabromobisphenol A (TBBPA) on reproductive development in rats","authors":"Mette Stub, Louise Ramhøj, Marta Axelstad, Mikael Pedersen, Terje Svingen","doi":"10.1016/j.reprotox.2026.109170","DOIUrl":"10.1016/j.reprotox.2026.109170","url":null,"abstract":"<div><div>Perfluorooctane sulfonate (PFOS) and tetrabromobisphenol A (TBBPA) are environmental pollutants with known endocrine disrupting potential. Both substances display various thyroid hormone (TH) system disrupting effects, both <em>in vitro</em> and <em>in vivo</em>, but effects on the reproductive system following developmental exposure are less characterized. Recently, we described effects following perinatal exposure to PFOS (0.4 or 0.8 mg/kg bw/day) and TBBPA (250 or 500 mg/kg bw/day) on the TH system in rats, showing a complex effect pattern. Here, we report data on reproductive endpoints (anogenital distance (AGD), nipple retention (NR) and male reproductive organ weights) and steroid hormone levels in offspring from the same <em>in vivo</em> study. Results indicate that PFOS and TBBPA do not affect antiandrogenic endpoints such as AGD and NR at administered doses. PFOS had a modest effect on steroidogenesis, increasing estrone levels in fetuses, and in the 16-day-old pups increasing corticosterone levels in the low-dose group and progesterone levels in both dose groups, along with a small reduction in adjusted testes weight. TBBPA did not alter steroid hormone levels at the fetal stage, but hormones were disrupted in the 16-day-old pups. Here TBBPA increased progesterone levels in low-dose and testosterone levels in high-dose pups and reduced estrone levels in high-dose group to values below the limit of quantification (LOQ). These findings suggest that PFOS and TBBPA have some effects on circulating steroid hormone levels, but minimal effects on androgen-sensitive endpoints in rats.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109170"},"PeriodicalIF":2.8,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998497","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

Cross-scale causal inference integrated with single-cell profiling and molecular simulations reveals a macrophage CSF1R–CD68–LYZ axis linking benzo[a]pyrene to erectile dysfunction 结合单细胞分析和分子模拟的跨尺度因果推理揭示了巨噬细胞CSF1R-CD68-LYZ轴将苯并[a]芘与勃起功能障碍联系起来。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-16 DOI: 10.1016/j.reprotox.2026.109169

Zuomin Wang , Guodong Ding , Yiwen Chen, Yuantang Zhong, Youwei Le, Qing Zhang, Wangdong Deng

Background

Erectile dysfunction (ED) is a common disorder with established risk factors such as cardiovascular disease, diabetes, and aging. Increasing evidence indicates that environmental exposures also contribute to its pathogenesis. Benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon in air pollution, tobacco smoke, and charred foods, has been linked to reproductive dysfunction, yet its molecular role in ED remains unclear.

Methods

A multi-faceted approach combining Mendelian randomization (MR), network toxicology, molecular simulations, single-cell RNA sequencing, and virtual gene knockout was used to explore the link between B[a]P exposure and ED. MR assessed causal associations, network toxicology identified molecular targets, and single-cell analysis revealed cellular responses, while virtual gene knockout validated key genes in ED.

Results

Our integrated analysis identified CSF1R, CD68, and LYZ as central genes in B[a]P-induced ED. These genes regulate macrophage-driven inflammation, which contributes to endothelial dysfunction and vascular damage—critical processes in ED pathophysiology. Direct interactions between B[a]P and these genes were confirmed, with macrophages playing a key role in the disease mechanism. Causal relationships between B[a]P exposure and ED were established, and therapeutic strategies targeting macrophage-specific genes were proposed to mitigate the impact of environmental toxins on erectile function.

Conclusions

This study offers novel insights into the role of B[a]P in ED and identifies key macrophage-specific genes as therapeutic targets. These findings suggest potential strategies for addressing B[a]P-induced ED, with future research needed to validate these targets and explore therapies targeting macrophage-driven inflammation.

背景：勃起功能障碍（ED）是一种常见的疾病，有心血管疾病、糖尿病和衰老等危险因素。越来越多的证据表明，环境暴露也有助于其发病机制。苯并[a]芘（B[a]P）是一种致癌的多环芳烃，存在于空气污染、烟草烟雾和烧焦的食物中，与生殖功能障碍有关，但其在ED中的分子作用尚不清楚。方法：采用孟德尔随机化（MR）、网络毒理学、分子模拟、单细胞RNA测序和虚拟基因敲除等多角度方法，探索B[A]P暴露与ED之间的联系。MR评估因果关系，网络毒理学确定分子靶点，单细胞分析揭示细胞反应，虚拟基因敲除验证ED中的关键基因。我们的综合分析发现CSF1R、CD68和LYZ是B[a] p诱导ED的中心基因。这些基因调节巨噬细胞驱动的炎症，这有助于ED病理生理中的内皮功能障碍和血管损伤关键过程。证实了B[a]P与这些基因之间的直接相互作用，巨噬细胞在疾病机制中起关键作用。研究建立了B[a]P暴露与ED之间的因果关系，并提出了针对巨噬细胞特异性基因的治疗策略，以减轻环境毒素对勃起功能的影响。结论：本研究为B[a]P在ED中的作用提供了新的见解，并确定了巨噬细胞特异性的关键基因作为治疗靶点。这些发现提示了解决B[a] p诱导ED的潜在策略，未来的研究需要验证这些靶点，并探索针对巨噬细胞驱动炎症的治疗方法。

{"title":"Cross-scale causal inference integrated with single-cell profiling and molecular simulations reveals a macrophage CSF1R–CD68–LYZ axis linking benzo[a]pyrene to erectile dysfunction","authors":"Zuomin Wang , Guodong Ding , Yiwen Chen, Yuantang Zhong, Youwei Le, Qing Zhang, Wangdong Deng","doi":"10.1016/j.reprotox.2026.109169","DOIUrl":"10.1016/j.reprotox.2026.109169","url":null,"abstract":"<div><h3>Background</h3><div>Erectile dysfunction (ED) is a common disorder with established risk factors such as cardiovascular disease, diabetes, and aging. Increasing evidence indicates that environmental exposures also contribute to its pathogenesis. Benzo[<em>a</em>]pyrene (B[<em>a</em>]P), a carcinogenic polycyclic aromatic hydrocarbon in air pollution, tobacco smoke, and charred foods, has been linked to reproductive dysfunction, yet its molecular role in ED remains unclear.</div></div><div><h3>Methods</h3><div>A multi-faceted approach combining Mendelian randomization (MR), network toxicology, molecular simulations, single-cell RNA sequencing, and virtual gene knockout was used to explore the link between B[<em>a</em>]P exposure and ED. MR assessed causal associations, network toxicology identified molecular targets, and single-cell analysis revealed cellular responses, while virtual gene knockout validated key genes in ED.</div></div><div><h3>Results</h3><div>Our integrated analysis identified CSF1R, CD68, and LYZ as central genes in B[<em>a</em>]P-induced ED. These genes regulate macrophage-driven inflammation, which contributes to endothelial dysfunction and vascular damage—critical processes in ED pathophysiology. Direct interactions between B[<em>a</em>]P and these genes were confirmed, with macrophages playing a key role in the disease mechanism. Causal relationships between B[<em>a</em>]P exposure and ED were established, and therapeutic strategies targeting macrophage-specific genes were proposed to mitigate the impact of environmental toxins on erectile function.</div></div><div><h3>Conclusions</h3><div>This study offers novel insights into the role of B[<em>a</em>]P in ED and identifies key macrophage-specific genes as therapeutic targets. These findings suggest potential strategies for addressing B[<em>a</em>]P-induced ED, with future research needed to validate these targets and explore therapies targeting macrophage-driven inflammation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109169"},"PeriodicalIF":2.8,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998535","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

Ethylene oxide impairs sperm motility through dysregulation of Rab proteins 环氧乙烷通过Rab蛋白的失调损害精子活力

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-12 DOI: 10.1016/j.reprotox.2026.109168

Jae-Hwan Jo , Uwamahoro Claudine , Seung-Ik Jang , Eun-Ju Jung , Woo-Jin Lee , Jeong-Won Bae , Daehyun Kim , Joonho Moon , Seung Won Nam , Eu Jin Chung , Junkoo Yi , Woo-Sung Kwon

Ethylene oxide (E.O) is an ether compound that negatively affects male reproduction, specifically by impairing sperm function. However, the molecular mechanisms underlying the E.O-induced inhibition of sperm function remain poorly understood. Therefore, this study investigated the molecular mechanisms behind E.O-induced toxic effects on sperm motility by assessing Ras-associated binding (Rab) proteins. Therefore, 31 individual Duroc semen samples were analyzed to determine the correlations between Rab protein (Rab3A, Rab5, Rab14, Rab25, Rab27A, and Rab34) levels and sperm motility after exposure to 100-μM E.O. The results showed that E.O exposure significantly reduced sperm motility and motion kinematics. Furthermore, correlation analysis revealed that, in the control group, Rab3A, Rab5, Rab14, Rab25, Rab27A, and Rab34 levels were correlated with various sperm motion parameters. In contrast, only Rab3A and Rab14 levels correlated with multiple sperm motility and kinematic parameters in the 100-μM-E.O group. These results suggest that E.O may affect sperm motion parameters via the action of Rab proteins, leading to decreased sperm motility. Consequently, these findings provide important evidence of the molecular mechanisms underlying E.O-induced toxic effects on sperm function.

环氧乙烷（E.O）是一种乙醚化合物，对男性生殖有负面影响，特别是通过损害精子功能。然而，e.o诱导的精子功能抑制的分子机制仍然知之甚少。因此，本研究通过评估ras相关结合蛋白（Rab）来研究e.o诱导的精子活力毒性作用的分子机制。因此，我们分析了31份杜洛克个体精液样本，以确定暴露于100 μ m E.O o后Rab蛋白（Rab3A、Rab5、Rab14、Rab25、Rab27A和Rab34）水平与精子活力的相关性。结果表明，E.O o暴露显著降低了精子活力和运动运动学。此外，相关分析显示，在对照组中，Rab3A、Rab5、Rab14、Rab25、Rab27A和Rab34的水平与精子的各种运动参数相关。相比之下，在100 μ m - e中，Rab3A和Rab14水平与多精子运动和运动学参数相关。O组。这些结果表明，E.O可能通过Rab蛋白的作用影响精子运动参数，导致精子运动能力下降。因此，这些发现为e.o诱导的精子功能毒性作用的分子机制提供了重要证据。

{"title":"Ethylene oxide impairs sperm motility through dysregulation of Rab proteins","authors":"Jae-Hwan Jo , Uwamahoro Claudine , Seung-Ik Jang , Eun-Ju Jung , Woo-Jin Lee , Jeong-Won Bae , Daehyun Kim , Joonho Moon , Seung Won Nam , Eu Jin Chung , Junkoo Yi , Woo-Sung Kwon","doi":"10.1016/j.reprotox.2026.109168","DOIUrl":"10.1016/j.reprotox.2026.109168","url":null,"abstract":"<div><div>Ethylene oxide (E.O) is an ether compound that negatively affects male reproduction, specifically by impairing sperm function. However, the molecular mechanisms underlying the E.O-induced inhibition of sperm function remain poorly understood. Therefore, this study investigated the molecular mechanisms behind E.O-induced toxic effects on sperm motility by assessing Ras-associated binding (Rab) proteins. Therefore, 31 individual Duroc semen samples were analyzed to determine the correlations between Rab protein (Rab3A, Rab5, Rab14, Rab25, Rab27A, and Rab34) levels and sperm motility after exposure to 100-μM E.O. The results showed that E.O exposure significantly reduced sperm motility and motion kinematics. Furthermore, correlation analysis revealed that, in the control group, Rab3A, Rab5, Rab14, Rab25, Rab27A, and Rab34 levels were correlated with various sperm motion parameters. In contrast, only Rab3A and Rab14 levels correlated with multiple sperm motility and kinematic parameters in the 100-μM-E.O group. These results suggest that E.O may affect sperm motion parameters via the action of Rab proteins, leading to decreased sperm motility. Consequently, these findings provide important evidence of the molecular mechanisms underlying E.O-induced toxic effects on sperm function.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109168"},"PeriodicalIF":2.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977165","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

Guarding the ovarian reserve: Maternal methyl donor supplementation protects against propylparaben-induced ovarian aging in offspring 保护卵巢储备：母体甲基供体补充可防止对羟基苯甲酸丙酯诱导的后代卵巢衰老。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-11 DOI: 10.1016/j.reprotox.2026.109167

Yaling Wu , Yi Chen , Shixuan Wang , Tong Wu , Jinjin Zhang

Prenatal exposure to endocrine-disrupting chemicals is increasingly recognized as a contributing factor to female reproductive aging. Propylparaben (PRP), a widely used preservative with estrogenic activity, is ubiquitously detected in human biological samples, raising concern regarding gestational exposure. However, how prenatal PRP exposure affects ovarian development and whether nutritional interventions confer protection remain unclear. Here, pregnant mice were exposed to PRP from embryonic day 7.5 to E13.5, with or without maternal methyl donor (MD) supplementation. Prenatal PRP exposure was associated with impaired primordial follicle pool establishment as early as postnatal day 7 and reduced ovarian reserve and fertility in adult offspring. These effects were associated with increased oxidative stress, inflammation, fibrotic remodeling, hyperactivation of PI3K/AKT/mTOR signaling, and aberrant DNA methylation, collectively contributing to premature follicle activation and depletion. Maternal MD supplementation partially mitigated PRP-induced ovarian injury, helped preserve follicle homeostasis, and improved reproductive outcomes, accompanied by partial restoration of DNA methylation and moderation of aberrant pathway activation. These findings suggest that maternal MD intake may offer a potential nutritional approach to mitigating long-term reproductive risks associated with prenatal PRP exposure.

产前接触干扰内分泌的化学物质越来越被认为是导致女性生殖老化的一个因素。对羟基苯甲酸丙酯（PRP）是一种广泛使用的具有雌激素活性的防腐剂，在人类生物样本中普遍存在，引起了人们对妊娠暴露的关注。然而，产前PRP暴露如何影响卵巢发育以及营养干预是否具有保护作用仍不清楚。在这里，怀孕小鼠从胚胎第7.5天到第13.5天暴露于PRP，添加或不添加母体甲基供体（MD）。产前PRP暴露与早在出生后第7天的原始卵泡池建立受损以及成年后代卵巢储备和生育能力降低有关。这些影响与氧化应激、炎症、纤维化重塑、PI3K/AKT/mTOR信号的过度激活以及异常的DNA甲基化有关，共同导致了早卵泡的激活和消耗。母体补充MD部分减轻了prp诱导的卵巢损伤，有助于保持卵泡稳态，改善生殖结果，同时部分恢复DNA甲基化和调节异常途径激活。这些发现表明，孕妇摄入MD可能提供一种潜在的营养途径，以减轻与产前PRP暴露相关的长期生殖风险。

{"title":"Guarding the ovarian reserve: Maternal methyl donor supplementation protects against propylparaben-induced ovarian aging in offspring","authors":"Yaling Wu , Yi Chen , Shixuan Wang , Tong Wu , Jinjin Zhang","doi":"10.1016/j.reprotox.2026.109167","DOIUrl":"10.1016/j.reprotox.2026.109167","url":null,"abstract":"<div><div>Prenatal exposure to endocrine-disrupting chemicals is increasingly recognized as a contributing factor to female reproductive aging. Propylparaben (PRP), a widely used preservative with estrogenic activity, is ubiquitously detected in human biological samples, raising concern regarding gestational exposure. However, how prenatal PRP exposure affects ovarian development and whether nutritional interventions confer protection remain unclear. Here, pregnant mice were exposed to PRP from embryonic day 7.5 to E13.5, with or without maternal methyl donor (MD) supplementation. Prenatal PRP exposure was associated with impaired primordial follicle pool establishment as early as postnatal day 7 and reduced ovarian reserve and fertility in adult offspring. These effects were associated with increased oxidative stress, inflammation, fibrotic remodeling, hyperactivation of PI3K/AKT/mTOR signaling, and aberrant DNA methylation, collectively contributing to premature follicle activation and depletion. Maternal MD supplementation partially mitigated PRP-induced ovarian injury, helped preserve follicle homeostasis, and improved reproductive outcomes, accompanied by partial restoration of DNA methylation and moderation of aberrant pathway activation. These findings suggest that maternal MD intake may offer a potential nutritional approach to mitigating long-term reproductive risks associated with prenatal PRP exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109167"},"PeriodicalIF":2.8,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966939","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 role of adenosine triphosphate in the treatment of linezolid-induced ovarian damage and reproductive dysfunction in rats: An investigation into the pathogenesis 三磷酸腺苷在治疗利奈唑胺诱导的大鼠卵巢损伤和生殖功能障碍中的作用：发病机制的探讨。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-09 DOI: 10.1016/j.reprotox.2026.109165

Ilhan Bahri Delibasi , Bulent Yavuzer , Bahadir Suleyman , Neset Gumusburun , Taha Abdulkadir Coban , Ali Sefa Mendil , Elif Esra Uyar , Nurinisa Yucel , Halis Suleyman

Linezolid is an oxazolidinone-derived antibacterial agent that inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit. This study investigated whether exogenously administered adenosine triphosphate (ATP) mitigates ovarian damage and reproductive dysfunction induced by linezolid in rats. Forty-eight female albino Wistar rats were randomly assigned to four groups (n = 12 each): healthy control (HG), ATP-only (ATPG), linezolid-only (LZDG), and ATP plus linezolid (ATLDG). ATPG and ATLDG received intraperitoneal ATP (4 mg/kg), whereas HG and LZDG received saline (0.9 % NaCl). One hour later, linezolid (125 mg/kg) was administered orally to LZDG and ATLDG, and the regimen was repeated twice daily for 28 consecutive days. At study end, six rats per group were euthanized for ovarian biochemical, histopathological, and immunohistochemical evaluations; prior to euthanasia (i.p. thiopental sodium, 50 mg/kg), blood was collected for serum prolactin and anti-Müllerian hormone (AMH) analysis. For fertility assessment, the remaining six females per group were co-housed with two proven fertile males for seven days and then monitored for pregnancy for one month. Linezolid exposure increased oxidative stress, caused ovarian tissue injury, decreased AMH, elevated prolactin, and resulted in a 66.7 % infertility rate. ATP co-treatment attenuated these alterations and reduced infertility to 33.3 %. These findings suggest that ATP may provide a protective therapeutic approach against linezolid-induced ovarian toxicity and reproductive dysfunction.

利奈唑胺是一种恶唑烷衍生的抗菌剂，通过与50S核糖体亚基的肽基转移酶中心结合来抑制细菌蛋白质的合成。本研究探讨外源性三磷酸腺苷（ATP）是否能减轻利奈唑胺引起的大鼠卵巢损伤和生殖功能障碍。将48只雌性白化Wistar大鼠随机分为健康对照组（HG）、单用ATP组（ATPG）、单用利奈唑胺组（LZDG）和ATP +利奈唑胺组（ATLDG），每组12只。ATPG和ATLDG腹腔注射ATP (4mg/kg)， HG和LZDG腹腔注射生理盐水（0.9% NaCl）。1 h后给予LZDG和ATLDG口服利奈唑胺（125mg/kg），每日重复2次，连续28天。研究结束时，每组处死6只大鼠，进行卵巢生化、组织病理学和免疫组织化学评价；安乐死前（口服硫喷妥钠，50mg/kg）采血进行血清催乳素和抗勒氏杆菌激素（AMH）分析。为了评估生育能力，每组剩下的6只雌性与两只证明有生育能力的雄性共处7天，然后监测怀孕一个月。利奈唑胺暴露增加氧化应激，引起卵巢组织损伤，AMH降低，催乳素升高，导致66.7%的不孕率。ATP联合治疗减轻了这些改变，将不孕症降低到33.3%。这些发现表明，ATP可能对利奈唑胺诱导的卵巢毒性和生殖功能障碍提供保护性治疗途径。

{"title":"The role of adenosine triphosphate in the treatment of linezolid-induced ovarian damage and reproductive dysfunction in rats: An investigation into the pathogenesis","authors":"Ilhan Bahri Delibasi , Bulent Yavuzer , Bahadir Suleyman , Neset Gumusburun , Taha Abdulkadir Coban , Ali Sefa Mendil , Elif Esra Uyar , Nurinisa Yucel , Halis Suleyman","doi":"10.1016/j.reprotox.2026.109165","DOIUrl":"10.1016/j.reprotox.2026.109165","url":null,"abstract":"<div><div>Linezolid is an oxazolidinone-derived antibacterial agent that inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit. This study investigated whether exogenously administered adenosine triphosphate (ATP) mitigates ovarian damage and reproductive dysfunction induced by linezolid in rats. Forty-eight female albino Wistar rats were randomly assigned to four groups (n = 12 each): healthy control (HG), ATP-only (ATPG), linezolid-only (LZDG), and ATP plus linezolid (ATLDG). ATPG and ATLDG received intraperitoneal ATP (4 mg/kg), whereas HG and LZDG received saline (0.9 % NaCl). One hour later, linezolid (125 mg/kg) was administered orally to LZDG and ATLDG, and the regimen was repeated twice daily for 28 consecutive days. At study end, six rats per group were euthanized for ovarian biochemical, histopathological, and immunohistochemical evaluations; prior to euthanasia (i.p. thiopental sodium, 50 mg/kg), blood was collected for serum prolactin and anti-Müllerian hormone (AMH) analysis. For fertility assessment, the remaining six females per group were co-housed with two proven fertile males for seven days and then monitored for pregnancy for one month. Linezolid exposure increased oxidative stress, caused ovarian tissue injury, decreased AMH, elevated prolactin, and resulted in a 66.7 % infertility rate. ATP co-treatment attenuated these alterations and reduced infertility to 33.3 %. These findings suggest that ATP may provide a protective therapeutic approach against linezolid-induced ovarian toxicity and reproductive dysfunction.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109165"},"PeriodicalIF":2.8,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952721","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

Effects of dexamethasone on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats 地塞米松对大鼠黄体甾体生成、细胞凋亡及PKA/CREB/PPARG通路的影响。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-09 DOI: 10.1016/j.reprotox.2026.109166

Jie Zhao , Xianyi Zhou , Hao Yu , Abdul Quddus , Xin Liu , Dagan Mao

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 corpora lutea, 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 (P < 0.05), and decreased high－density lipoprotein cholesterol and low－density lipoprotein cholesterol levels (P < 0.05). Dex treatment increased serum P4 level (P < 0.05), as well as ovarian mRNA abundances of Star and Cyp11a1 (P < 0.05), and protein levels of StAR and HSD3B (P < 0.05); Dex also increased the Bax/Bcl-2 ratio at both mRNA and protein levels (P < 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 (P < 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.

本研究旨在探讨地塞米松（Dex）对大鼠黄体甾体生成、细胞凋亡及PKA/CREB/PPARG通路的影响。28日龄大鼠经PMSG和hCG处理获得一定量的黄体，然后注射右美托咪唑（右美托咪唑组）或生理盐水（对照组，对照组），持续7 d。采集血清，采用相应试剂盒检测生化指标，RIA检测孕酮（P4）水平。收集卵巢进行HE、IHC和TUNEL分析，并分别采用real-time PCR和western blotting检测与甾体生成和凋亡相关的基因和蛋白，包括PKA/CREB/PPARG成员。结果显示，右美托咪唑治疗大鼠血清甘油三酯和葡萄糖水平升高（P < 0.05），高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平降低（P < 0.05）。Dex组血清P4水平升高（P < 0.05），卵巢Star、Cyp11a1 mRNA丰度升高（P < 0.05）， Star、HSD3B蛋白水平升高（P < 0.05）；Dex在mRNA和蛋白水平上均提高了Bax/Bcl-2比值(P

{"title":"Effects of dexamethasone on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats","authors":"Jie Zhao , Xianyi Zhou , Hao Yu , Abdul Quddus , Xin Liu , 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> < 0.05), and decreased high－density lipoprotein cholesterol and low－density lipoprotein cholesterol levels (<em>P</em> < 0.05). Dex treatment increased serum P4 level (<em>P</em> < 0.05), as well as ovarian mRNA abundances of <em>Star</em> and <em>Cyp11a1</em> (<em>P</em> < 0.05), and protein levels of StAR and HSD3B (<em>P</em> < 0.05); Dex also increased the Bax/Bcl-2 ratio at both mRNA and protein levels (<em>P</em> < 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> < 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":"2026-01-09","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}

引用次数: 0

Clonidine compromises human sperm functions 可乐定会损害人类精子功能

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-08 DOI: 10.1016/j.reprotox.2026.109164

Xuchang Liu , Yanfan Cui , Ruirui Qian , Yixuan Li , Zeyu Hu , Houyang Chen , Yufeng Yuan , Tao Luo

Although clonidine, a widely prescribed α2-adrenergic agonist for hypertension and attention deficit hyperactivity disorder (ADHD), has unknown effects on male fertility. This study investigated clonidine's impact on human sperm function and progesterone-induced signaling pathways essential for fertilization. To address this knowledge gap, human sperm from normozoospermic donors (n ≥ 4 per experiment) were exposed to clonidine (6.25–200 μM) and analyzed using comprehensive approaches. Key experiments includedviability assessment (eosin staining), motility evaluation Computer-Aided Sperm Analysis (CASA), intracellular calcium measurement, patch-clamp electrophysiology, mitochondrial membrane potential, reactive oxygen species quantification, capacitation analysis (chlortetracycline staining), and protein phosphorylation (Western blot). The results demonstrated that clonidine exhibited biphasic effects, where concentrations ≤ 50 μM preserved sperm viability and motility while inducing calcium responses, whereas concentrations ≥ 100 μM caused cytotoxicity. Most significantly, clonidine potently inhibited progesterone-induced calcium signaling, capacitation, and acrosome reaction while preserving spontaneous processes, and electrophysiological studies indicated partial Cation channel of Sperm (CatSper channel) enhancement with ∼50 % channel involvement in clonidine's calcium effects. Cation channel of Sperm (CatSper channel) enhancement with ∼50 % channel involvement in clonidine's calcium effects. These findings reveal that clonidine selectively interferes with progesterone-induced sperm responses while maintaining baseline functions, representing a novel mechanism affecting male fertility in vitro, which warrants further investigation regarding its potential clinical relevance.

虽然可乐定是一种广泛用于治疗高血压和注意缺陷多动障碍（ADHD）的α - 2肾上腺素能激动剂，但它对男性生育能力的影响尚不清楚。本研究探讨了可乐定对人类精子功能和黄体酮诱导的受精所需信号通路的影响。为了解决这一知识空白，我们将正常精子供体（n次 ≥ 4次）的精子暴露于可乐定（6.25-200 μM）中，并采用综合方法进行分析。关键实验包括活力评估（伊红染色）、活力评估计算机辅助精子分析（CASA）、细胞内钙测量、膜片钳电生理、线粒体膜电位、活性氧定量、获能分析（氯四环素染色）和蛋白质磷酸化（Western blot）。结果表明，可乐定具有双相效应，浓度≤ 50 μM可在诱导钙反应的同时保持精子活力和活力，而浓度≥ 100 μM可引起细胞毒性。最重要的是，可乐定能有效抑制黄体酮诱导的钙信号、能化和顶体反应，同时保留自发过程，电生理研究表明，可乐定的钙效应中，精子部分阳离子通道（CatSper通道）增强，约50% %的通道参与其中。精子阳离子通道（CatSper通道）增强，约50% %通道参与可乐定的钙效应。这些发现表明，可乐定选择性地干扰黄体酮诱导的精子反应，同时保持基线功能，代表了一种影响体外男性生育能力的新机制，值得进一步研究其潜在的临床意义。

{"title":"Clonidine compromises human sperm functions","authors":"Xuchang Liu , Yanfan Cui , Ruirui Qian , Yixuan Li , Zeyu Hu , Houyang Chen , Yufeng Yuan , Tao Luo","doi":"10.1016/j.reprotox.2026.109164","DOIUrl":"10.1016/j.reprotox.2026.109164","url":null,"abstract":"<div><div>Although clonidine, a widely prescribed α2-adrenergic agonist for hypertension and attention deficit hyperactivity disorder (ADHD), has unknown effects on male fertility. This study investigated clonidine's impact on human sperm function and progesterone-induced signaling pathways essential for fertilization. To address this knowledge gap, human sperm from normozoospermic donors (n ≥ 4 per experiment) were exposed to clonidine (6.25–200 μM) and analyzed using comprehensive approaches. Key experiments includedviability assessment (eosin staining), motility evaluation Computer-Aided Sperm Analysis (CASA), intracellular calcium measurement, patch-clamp electrophysiology, mitochondrial membrane potential, reactive oxygen species quantification, capacitation analysis (chlortetracycline staining), and protein phosphorylation (Western blot). The results demonstrated that clonidine exhibited biphasic effects, where concentrations ≤ 50 μM preserved sperm viability and motility while inducing calcium responses, whereas concentrations ≥ 100 μM caused cytotoxicity. Most significantly, clonidine potently inhibited progesterone-induced calcium signaling, capacitation, and acrosome reaction while preserving spontaneous processes, and electrophysiological studies indicated partial Cation channel of Sperm (CatSper channel) enhancement with ∼50 % channel involvement in clonidine's calcium effects. Cation channel of Sperm (CatSper channel) enhancement with ∼50 % channel involvement in clonidine's calcium effects. These findings reveal that clonidine selectively interferes with progesterone-induced sperm responses while maintaining baseline functions, representing a novel mechanism affecting male fertility in vitro, which warrants further investigation regarding its potential clinical relevance.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109164"},"PeriodicalIF":2.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925610","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

MicroRNAs in fetal alcohol spectrum disorders: A systematic review of prenatal exposure and molecular targets 胎儿酒精谱系障碍中的microrna：产前暴露和分子靶点的系统综述。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-01-08 DOI: 10.1016/j.reprotox.2026.109163

Samane Jahanabadi , Houman Alimoradi , Ali Razmi

Background

Fetal alcohol spectrum disorder (FASD), caused by prenatal ethanol exposure, encompasses developmental abnormalities such as craniofacial dysmorphism, sensory and motor impairments, and neurocognitive deficits. MicroRNAs have been proposed as key regulators in FASD pathophysiology, yet the specific molecular pathways they influence remain unclear.

Methods

To better understand the role of microRNAs in the progression of FASD, we have systematically reviewed the effects of prenatal exposure to alcohol on microRNAs. The search was performed through PubMed MEDLINE, web of science, Scopus, and Google Scholar for all articles between 2006 and 2025.

Results

The range of ethanol concentrations as well as exposure pattern which applied in the animal models were widely distributed. Totally, 241 differentially expressed microRNAs were identified from 36 experimentally published reports. Emerging data have implicated that special miRNAs are involved in apoptosis (e.g., miR-335, miR-21, miR-9, miR-29a), axon guidance (e.g., miR-17–5p, miR-10b-3p, let-7a-3p, let-7g-3p, let-7i-3p), cell migration/proliferation (e.g., miR760, miR-98–5p, miR-378a-3p), and up- or downregulations of proteins associated with FASD’s abnormalities.

Conclusions

Despite substantial heterogeneity in experimental designs, including differences in model systems, species, dosing regimens, and exposure durations, several microRNAs (miR‑9, miR‑335, miR‑15b, miR‑34a, let‑7i, miR‑200a, and miR‑326) consistently emerge as key regulators implicated in the pathophysiology of fetal alcohol spectrum disorders.

背景：胎儿酒精谱系障碍（FASD）是由产前乙醇暴露引起的，包括发育异常，如颅面畸形、感觉和运动障碍以及神经认知缺陷。microrna已被认为是FASD病理生理的关键调节因子，但它们影响的具体分子途径尚不清楚。方法：为了更好地了解microrna在FASD进展中的作用，我们系统地回顾了产前暴露于酒精对microrna的影响。通过PubMed MEDLINE、web of science、Scopus和b谷歌Scholar对2006年至2025年间的所有文章进行了搜索。结果：应用于动物模型的乙醇浓度范围和暴露方式分布广泛。总共从37篇实验发表的报告中鉴定出241个差异表达的microrna。新出现的数据表明，特殊的mirna参与细胞凋亡（如miR-335、miR-21、miR-9、miR-29a）、轴突引导（如miR-17-5p、miR-10b-3p、let-7a-3p、let-7g-3p、let-7i-3p）、细胞迁移/增殖（如miR760、miR-98-5p、miR-378a-3p）以及与FASD异常相关的蛋白的上调或下调。结论：尽管实验设计存在很大的异质性，包括模型系统、物种、给药方案和暴露时间的差异，但几种microrna （miR - 9、miR - 335、miR - 15b、miR - 34a、let - 7i、miR - 200a和miR - 326）始终是胎儿酒精谱系障碍病理生理学中涉及的关键调节因子。

{"title":"MicroRNAs in fetal alcohol spectrum disorders: A systematic review of prenatal exposure and molecular targets","authors":"Samane Jahanabadi , Houman Alimoradi , Ali Razmi","doi":"10.1016/j.reprotox.2026.109163","DOIUrl":"10.1016/j.reprotox.2026.109163","url":null,"abstract":"<div><h3>Background</h3><div>Fetal alcohol spectrum disorder (FASD), caused by prenatal ethanol exposure, encompasses developmental abnormalities such as craniofacial dysmorphism, sensory and motor impairments, and neurocognitive deficits. MicroRNAs have been proposed as key regulators in FASD pathophysiology, yet the specific molecular pathways they influence remain unclear.</div></div><div><h3>Methods</h3><div>To better understand the role of microRNAs in the progression of FASD, we have systematically reviewed the effects of prenatal exposure to alcohol on microRNAs. The search was performed through PubMed MEDLINE, web of science, Scopus, and Google Scholar for all articles between 2006 and 2025.</div></div><div><h3>Results</h3><div>The range of ethanol concentrations as well as exposure pattern which applied in the animal models were widely distributed. Totally, 241 differentially expressed microRNAs were identified from 36 experimentally published reports. Emerging data have implicated that special miRNAs are involved in apoptosis (e.g., miR-335, miR-21, miR-9, miR-29a), axon guidance (e.g., miR-17–5p, miR-10b-3p, let-7a-3p, let-7g-3p, let-7i-3p), cell migration/proliferation (e.g., miR760, miR-98–5p, miR-378a-3p), and up- or downregulations of proteins associated with FASD’s abnormalities.</div></div><div><h3>Conclusions</h3><div>Despite substantial heterogeneity in experimental designs, including differences in model systems, species, dosing regimens, and exposure durations, several microRNAs (miR‑9, miR‑335, miR‑15b, miR‑34a, let‑7i, miR‑200a, and miR‑326) consistently emerge as key regulators implicated in the pathophysiology of fetal alcohol spectrum disorders.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109163"},"PeriodicalIF":2.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949028","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