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精子中的瞬时受体电位香草酸亚型1（TRPV1）通道是活性氧介导的精子功能障碍的分子靶点，在自然妊娠失败和辅助生殖技术妊娠失败中均有差异表达。

TRPV1 channel in spermatozoa is a molecular target for ROS-mediated sperm dysfunction and differentially expressed in both natural and ART pregnancy failure.

作者信息

Swain Nirlipta, Samanta Luna, Goswami Chandan, Kar Sujata, Majhi Rakesh Kumar, Kumar Sugandh, Dixit Anshuman

机构信息

Redox Biology & Proteomics Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Cuttack, Odisha, India.

School of Biological Sciences, National Institute of Science Education and Research, HBNI, Khordha, Odisha, India.

出版信息

Front Cell Dev Biol. 2022 Sep 23;10:867057. doi: 10.3389/fcell.2022.867057. eCollection 2022.

DOI:10.3389/fcell.2022.867057
PMID:36211461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9538505/
Abstract

Bi-directional crosstalk between Ca signaling and ROS modulates physiological processes as a part of a regulatory circuit including sperm function. The role of transient receptor potential vanilloid 1 (TRPV1) in this regard cannot be undermined. This is the first report demonstrating the Ca-sensitive TRPV1 channel to be under-expressed in spermatozoa of subfertile men, idiopathic infertile men, and normozoospermic infertile males with high ROS (idiopathic infertility and unilateral varicocele). To study the effect of TRPV1 in determining the fertility outcome, we compared the expression profile of TRPV1 in spermatozoa of male partners who achieved pregnancy by natural conception (NC+, = 10), IVF (IVF+, = 23), or ICSI (ICSI +, = 9) and their respective counterparts with failed pregnancy NC ( = 7), IVF ( = 23), or ICSI ( = 10), by both immunocytochemistry and flow-cytometry. Reduced expression of TRPV1 in sperm of IVF ± and ICSI ± men with respect to that NC+ men imply its role in mediating successful fertilization. Unsuccessful pregnancy outcome with an underexpression of TRPV1 in sperm of NC-/IVF-/ICSI-men suggests its role in conception and maintenance of pregnancy. Since ROS is regarded as one of the major contributors to sperm dysfunction, the effect of HO +/- TRPV1 modulators (RTX/iRTX) on acrosomal reaction and calcium influx was evaluated to confirm TRPV1 as a redox sensor in human sperm. A significant increment in the percentage of acrosome reacted spermatozoa along with augmented Ca-influx was observed after HO treatment, both in the presence or absence of TRPV1 agonist resiniferatoxin (RTX). The effect was attenuated by the TRPV1 antagonist iodoresiniferatoxin (iRTX), indicating the involvement of TRPV1 in mediating HO response. Enhancement of motility and triggering of acrosomal reaction post TRPV1 activation suggested that disruption of these signaling cascades , possibly due to down-regulation of TRPV1 in these subfertile males. Bioinformatic analysis of the crosstalk between TRPV1 with fertility candidate proteins (reported to influence IVF outcome) revealed cell death and survival, cellular compromise, and embryonic development to be the primary networks affected by anomalous TRPV1 expression. We therefore postulate that TRPV1 can act as a redox sensor, and its expression in spermatozoa may serve as a fertility marker.

摘要

钙信号与活性氧（ROS）之间的双向串扰作为包括精子功能在内的调节回路的一部分，调节生理过程。在这方面，瞬时受体电位香草酸受体1（TRPV1）的作用不可忽视。这是第一份报告，证明钙敏感的TRPV1通道在不育男性、特发性不育男性以及高ROS水平的正常精子不育男性（特发性不育和单侧精索静脉曲张）的精子中表达不足。为了研究TRPV1在决定生育结果中的作用，我们通过免疫细胞化学和流式细胞术比较了通过自然受孕（NC +，n = 10）、体外受精（IVF +，n = 23）或卵胞浆内单精子注射（ICSI +，n = 9）成功怀孕的男性伴侣的精子中TRPV1的表达谱，以及他们各自对应未成功怀孕的NC（n = 7）、IVF（n = 23）或ICSI（n = 10）男性伴侣的精子中TRPV1的表达谱。与NC +男性相比，IVF ±和ICSI ±男性精子中TRPV1表达降低，这意味着其在介导成功受精中的作用。NC -/IVF -/ICSI -男性精子中TRPV1表达不足且妊娠结果未成功，表明其在受孕和维持妊娠中的作用。由于ROS被认为是精子功能障碍的主要原因之一，因此评估了HO +/- TRPV1调节剂（RTX/iRTX）对顶体反应和钙内流的影响，以确认TRPV1作为人类精子中的氧化还原传感器。在存在或不存在TRPV1激动剂树脂毒素（RTX）的情况下，HO处理后均观察到顶体反应精子百分比显著增加以及钙内流增加。TRPV1拮抗剂碘树脂毒素（iRTX）减弱了这种作用，表明TRPV1参与介导HO反应。TRPV1激活后运动能力增强和顶体反应触发表明，这些信号级联的破坏可能是由于这些不育男性中TRPV1的下调所致。对TRPV1与生育候选蛋白（据报道影响IVF结果）之间串扰的生物信息学分析表明，细胞死亡和存活、细胞损伤以及胚胎发育是受异常TRPV1表达影响的主要网络。因此，我们推测TRPV1可以作为氧化还原传感器，其在精子中的表达可能作为生育标志物。

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本文引用的文献

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Int J Mol Sci. 2021 Apr 21;22(9):4306. doi: 10.3390/ijms22094306.
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Role of the TRPV Channels in the Endoplasmic Reticulum Calcium Homeostasis.TRPV 通道在内质网钙稳态中的作用。
Cells. 2020 Jan 28;9(2):317. doi: 10.3390/cells9020317.
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The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword.氧化应激在决定哺乳动物精子功能中的重要性：一把双刃剑
Antioxidants (Basel). 2020 Jan 27;9(2):111. doi: 10.3390/antiox9020111.
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Aberrant Upregulation of Compensatory Redox Molecular Machines May Contribute to Sperm Dysfunction in Infertile Men with Unilateral Varicocele: A Proteomic Insight.代偿性氧化还原分子机器的异常上调可能导致单侧精索静脉曲张不育男性精子功能障碍：蛋白质组学研究。
Antioxid Redox Signal. 2020 Mar 10;32(8):504-521. doi: 10.1089/ars.2019.7828. Epub 2019 Dec 12.
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Crosstalk between Calcium and ROS in Pathophysiological Conditions.钙与活性氧在病理生理条件下的相互作用。
Oxid Med Cell Longev. 2019 Apr 24;2019:9324018. doi: 10.1155/2019/9324018. eCollection 2019.
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Similarities Between Embryo Development and Cancer Process Suggest New Strategies for Research and Therapy of Tumors: A New Point of View.胚胎发育与癌症进程之间的相似性为肿瘤研究与治疗提示新策略：一种新观点
Front Cell Dev Biol. 2019 Mar 7;7:20. doi: 10.3389/fcell.2019.00020. eCollection 2019.
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Developmental Axon Degeneration Requires TRPV1-Dependent Ca Influx.发育性轴突退化需要 TRPV1 依赖性 Ca2+内流。
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Molecular and functional insights into Transient Receptor Potential Vanilloid 1 (TRPV1) in bull spermatozoa.公牛精子中瞬时受体电位香草酸亚型1（TRPV1）的分子与功能研究
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