Delgado-Bermúdez Ariadna, Recuero Sandra, Llavanera Marc, Mateo-Otero Yentel, Sandu Andra, Barranco Isabel, Ribas-Maynou Jordi, Yeste Marc
Biotechnology of Animal and Human Reproduction (TechnoSperm), Institute of Food and Agricultural Technology, University of Girona, Girona, Spain.
Unit of Cell Biology, Department of Biology, Faculty of Sciences, University of Girona, Girona, Spain.
Front Cell Dev Biol. 2021 Sep 1;9:656438. doi: 10.3389/fcell.2021.656438. eCollection 2021.
Aquaporins are a family of ubiquitous transmembrane proteins that allow the transport of water and small molecules across the cell plasma membrane. The different members of this family present a characteristic distribution across different cell types, which is species-specific. In mammalian sperm, different AQPs, including AQP3, AQP7, and AQP11, have been identified; their main roles are related to osmoadaptation and sperm motility activation after ejaculation. Capacitation, which is a post-ejaculatory process that sperm must undergo to achieve fertilizing ability, is triggered by pH changes and different extracellular ions that are present in the female reproductive tract. Considering the function of AQPs and their influence on pH through the regulation of water flow, this study aimed to elucidate the potential role of different AQPs during sperm capacitation using three different transition metal compounds as AQP inhibitors. Cooper sulfate, a specific inhibitor of AQP3, caused a drastic increase in peroxide intracellular levels compared to the control. Mercury chloride, an unspecific inhibitor of all AQPs except AQP7 produced an increase in membrane lipid disorder and led to a decrease in sperm motility and kinetics parameters. Finally, the addition of silver sulfadiazine, an unspecific inhibitor of all AQPs, generated the same effects than mercury chloride, decreased the intracellular pH and altered tyrosine phosphorylation levels after the induction of the acrosome reaction. In the light of the aforementioned, (a) the permeability of AQP3 to peroxides does not seem to be crucial for sperm capacitation and acrosome reaction; (b) AQPs have a key role in preserving sperm motility during that process; and (c) AQPs as a whole seem to contribute to the maintenance of lipid membrane architecture during capacitation and may be related to the intracellular signaling pathways involved in the acrosome reaction. Hence, further research aimed to elucidate the mechanisms underlying the involvement of AQPs in mammalian sperm capacitation and acrosome reaction is warranted.
水通道蛋白是一类普遍存在的跨膜蛋白，可允许水和小分子穿过细胞质膜。该家族的不同成员在不同细胞类型中呈现出特征性分布，这具有物种特异性。在哺乳动物精子中，已鉴定出不同的水通道蛋白，包括水通道蛋白3、水通道蛋白7和水通道蛋白11；它们的主要作用与渗透压适应以及射精后精子运动激活有关。获能是精子为获得受精能力而必须经历的射精后过程，由雌性生殖道中存在的pH变化和不同细胞外离子触发。考虑到水通道蛋白的功能及其通过调节水流对pH的影响，本研究旨在使用三种不同的过渡金属化合物作为水通道蛋白抑制剂，阐明不同水通道蛋白在精子获能过程中的潜在作用。硫酸铜是水通道蛋白3的特异性抑制剂，与对照组相比，它导致细胞内过氧化物水平急剧增加。氯化汞是除水通道蛋白7外所有水通道蛋白的非特异性抑制剂，它导致膜脂质紊乱增加，并导致精子活力和动力学参数降低。最后，添加磺胺嘧啶银，一种所有水通道蛋白的非特异性抑制剂，产生了与氯化汞相同的效果，降低了细胞内pH，并在诱导顶体反应后改变了酪氨酸磷酸化水平。鉴于上述情况，（a）水通道蛋白3对过氧化物的通透性似乎对精子获能和顶体反应并不关键；（b）水通道蛋白在此过程中对维持精子活力起关键作用；（c）水通道蛋白整体似乎有助于在获能过程中维持脂质膜结构，并且可能与顶体反应中涉及的细胞内信号通路有关。因此，有必要进行进一步研究以阐明水通道蛋白参与哺乳动物精子获能和顶体反应的潜在机制。
