Ryu Do-Yeal, Pang Won-Ki, Rahman Md Saidur, Park Yoo-Jin, Pang Myung-Geol
Department of Animal Science & Technology and BET Research Institute, Chung-Ang University, Anseong, Gyeonggi-do 17546, Republic of Korea; Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Department of Animal Science & Technology and BET Research Institute, Chung-Ang University, Anseong, Gyeonggi-do 17546, Republic of Korea.
Toxicology. 2025 Sep;516:154182. doi: 10.1016/j.tox.2025.154182. Epub 2025 May 9.
Bisphenol A (BPA) is an endocrine-disrupting chemical that is increasingly becoming a vital factor in public health due to its ubiquity and toxicity. BPA is associated with male infertility via the disrupted function of Leydig and Sertoli cells. Despite extensive research, the current understanding of the specific pathological concentrations and the mechanisms following BPA exposure still remain questionable. Therefore, we investigated the susceptibilities and underlying mechanisms in Leydig and Sertoli cells following treatment with various BPA doses (0.0001-100 µM in a 10-fold serial dilution). Our results showed that the lowest BPA levels (10 μM) decreased mitochondrial membrane potential and ATP levels. In contrast, ROS levels were increased at high BPA levels regardless of exposure time (24 or 48 h) in both cell types. Mitochondrial-mediated apoptosis was identified along with increased ROS levels and abnormal mitochondrial dynamics, but both cell types showed different susceptibility to BPA toxicity. Subsequently, BPA had detrimental impacts on the mRNA expression levels of steroidogenic enzymes and testosterone synthesis in Leydig cells and reduced anchoring junction proteins in Sertoli cells. Consequently, our results demonstrated that both cells were affected via estrogen receptor alpha. However, protein kinase A was oppositely expressed following BPA exposure in each cell type. Therefore, it is plausible to suggest that each cell has distinct sensitivities and mechanisms in response to BPA.
双酚A（BPA）是一种内分泌干扰化学物质，由于其无处不在和毒性，正日益成为公共卫生领域的一个关键因素。BPA通过睾丸间质细胞和支持细胞功能紊乱与男性不育相关。尽管进行了广泛研究，但目前对BPA暴露后的具体病理浓度和机制的理解仍存在疑问。因此，我们研究了用不同剂量BPA（以10倍系列稀释，浓度为0.0001 - 100 μM）处理后睾丸间质细胞和支持细胞的易感性及潜在机制。我们的结果表明，最低BPA水平（10 μM）会降低线粒体膜电位和ATP水平。相反，在两种细胞类型中，无论暴露时间（24或48小时）如何，高BPA水平时ROS水平都会升高。随着ROS水平升高和线粒体动力学异常，可确定存在线粒体介导的细胞凋亡，但两种细胞类型对BPA毒性表现出不同的易感性。随后，BPA对睾丸间质细胞中类固醇生成酶的mRNA表达水平和睾酮合成有不利影响，并降低了支持细胞中的锚定连接蛋白。因此，我们的结果表明两种细胞均通过雌激素受体α受到影响。然而，在每种细胞类型中，BPA暴露后蛋白激酶A的表达情况相反。因此，有理由认为每种细胞对BPA的反应具有不同的敏感性和机制。
