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HPV 感染通过抑制水通道蛋白 8 影响人类精子功能。

HPV Infection Affects Human Sperm Functionality by Inhibition of Aquaporin-8.

机构信息

Department of Molecular Medicine, Human Physiology Unit, University of Pavia, I-27100 Pavia, Italy.

Center for Reproductive Medicine, Obstetrics and Gynecology Unit, Fondazione IRCCS Policlinico San Matteo, University of Pavia, I-27100 Pavia, Italy.

出版信息

Cells. 2020 May 17;9(5):1241. doi: 10.3390/cells9051241.

Abstract

Human sperm cells express different aquaporins (AQPs), AQP3, 7, 8, 11, which are localized both in the plasma membrane and in intracellular structures. Besides cell volume regulation and end stage of cytoplasm removal during sperm maturation, the role of AQPs extends also to reactive oxygen species (ROS) elimination. Moreover, oxidative stress has been shown to inhibit AQP-mediated HO permeability. A decrease in AQPs functionality is related to a decrease in sperm cells number and motility. Here we investigate the possible effect of human Papillomavirus (HPV) on both expression and function of AQPs in human sperm cells of patients undergoing infertility couple evaluation. Stopped-flow light-scattering experiments demonstrated that HPV infection heavily reduced water permeability of sperm cells in normospermic samples. Confocal immunofluorescence experiments showed a colocalization of HPV L1 protein with AQP8 (Pearson's correlation coefficient of 0.61), confirmed by co-immunoprecipitation experiments. No interaction of HPV with AQP3 and AQP7 was observed. A 3D model simulation of L1 protein and AQP8 interaction was also performed. Present findings may suggest that HPV infection directly inhibits AQP8 functionality and probably makes sperm cells more sensitive to oxidative stress.

摘要

人类精子细胞表达不同的水通道蛋白(AQPs),包括 AQP3、7、8、11,它们定位于质膜和细胞内结构中。除了在精子成熟过程中调节细胞体积和去除细胞质末端外,AQPs 的作用还扩展到清除活性氧(ROS)。此外,氧化应激已被证明抑制 AQP 介导的 HO 通透性。AQPs 功能的降低与精子数量和活力的降低有关。在这里,我们研究了人乳头瘤病毒(HPV)对接受不孕夫妇评估的患者精子细胞中 AQPs 的表达和功能的可能影响。停流光散射实验表明,HPV 感染严重降低了正常精子样本中精子的水通透性。共聚焦免疫荧光实验显示 HPV L1 蛋白与 AQP8 存在共定位(皮尔逊相关系数为 0.61),并通过共免疫沉淀实验得到证实。未观察到 HPV 与 AQP3 和 AQP7 的相互作用。还进行了 L1 蛋白和 AQP8 相互作用的 3D 模型模拟。目前的发现可能表明 HPV 感染直接抑制 AQP8 的功能,并可能使精子细胞对氧化应激更敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b737/7291193/5d45f94c5169/cells-09-01241-g001.jpg

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