Research Group of Intracellular Signaling and Technology of Reproduction (SINTREP), Institute of Biotechnology in Agriculture and Livestock (INBIO G+C), University of Extremadura, 10003 Cáceres, Spain.
Research Unit, Complejo Hospitalario Universitario de Cáceres, 10003 Cáceres, Spain.
Int J Mol Sci. 2023 May 31;24(11):9598. doi: 10.3390/ijms24119598.
Bisphenol A (BPA: 2,3-bis (4-hydroxyphenyl) propane) is an environmental chemical widely used in the manufacturing of epoxy polymers and many thermoplastic consumer products. Serious concerns about its safety led to the development of analogs, such as BPS (4-hydroxyphenyl sulfone). Very limited studies about BPS's impact on reproduction, specifically in spermatozoa, exist in comparison with BPA. Therefore, this work aims to study the in vitro impact of BPS in pig spermatozoa in comparison with BPA, focusing on sperm motility, intracellular signaling pathways and functional sperm parameters. We have used porcine spermatozoa as an optimal and validated in vitro cell model to investigate sperm toxicity. Pig spermatozoa were exposed to 1 and 100 μM BPS or BPA for 3 and 20 h. Both bisphenol S and A (100 μM) significantly reduce pig sperm motility in a time-dependent manner, although BPS exerts a lower and slower effect than BPA. Moreover, BPS (100 μM, 20 h) causes a significant increase in the mitochondrial reactive species, whereas it does not affect sperm viability, mitochondrial membrane potential, cell reactive oxygen species, GSK3α/β phosphorylation or phosphorylation of PKA substrates. However, BPA (100 μM, 20 h) leads to a decrease in sperm viability, mitochondrial membrane potential, GSK3β phosphorylation and PKA phosphorylation, also causing an increase in cell reactive oxygen species and mitochondrial reactive species. These intracellular effects and signaling pathways inhibited might contribute to explaining the BPA-triggered reduction in pig sperm motility. However, the intracellular pathways and mechanisms triggered by BPS are different, and the BPS-caused reduction in motility can be only partially attributed to an increase in mitochondrial oxidant species.
双酚 A（BPA：2,3-双（4-羟苯基）丙烷）是一种广泛用于制造环氧树脂和许多热塑性消费品的环境化学物质。对其安全性的严重担忧导致了类似物的开发，例如 BPS（4-羟苯基砜）。与 BPA 相比，关于 BPS 对生殖系统的影响，特别是对精子的影响，研究非常有限。因此，这项工作旨在研究 BPS 对猪精子的体外影响，并与 BPA 进行比较，重点研究精子运动、细胞内信号通路和功能精子参数。我们使用猪精子作为一种优化和验证的体外细胞模型来研究精子毒性。猪精子分别暴露于 1 和 100 μM BPS 或 BPA 3 和 20 小时。双酚 S 和 A（100 μM）均显著降低猪精子的运动能力，且呈时间依赖性，尽管 BPS 的作用较弱且较慢。此外，BPS（100 μM，20 小时）会导致线粒体活性物质显著增加，而不会影响精子活力、线粒体膜电位、细胞活性氧、GSK3α/β磷酸化或 PKA 底物的磷酸化。然而，BPA（100 μM，20 小时）会导致精子活力、线粒体膜电位、GSK3β磷酸化和 PKA 磷酸化降低，同时导致细胞活性氧和线粒体活性物质增加。这些被抑制的细胞内效应和信号通路可能有助于解释 BPA 引起的猪精子运动能力下降。然而，BPS 触发的细胞内途径和机制不同，BPS 引起的运动能力下降只能部分归因于线粒体氧化剂种类的增加。
