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孕激素和内源性大麻素受体在调控公牛精子获能和顶体反应中的相互作用机制。

Interplay mechanisms between progesterone and endocannabinoid receptors in regulating bull sperm capacitation and acrosome reaction.

机构信息

Department of Veterinary Physiology, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deendayal Upadhayaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan, Mathura, Uttar Pradesh, India.

Sperm Signaling Laboratory, Department of Veterinary Physiology, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deendayal Upadhayaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan, Mathura, Uttar Pradesh, India.

出版信息

J Cell Physiol. 2022 Jul;237(7):2888-2912. doi: 10.1002/jcp.30753. Epub 2022 Apr 27.

DOI:10.1002/jcp.30753
PMID:35476800
Abstract

After ejaculation, sperm show a limited capacity for transcription and translation. In the oviduct, most of the signalling in sperm is nongenomic and is mediated through membrane receptors. Studies have shown that the cation channel of sperm (CatSper), cAMP, cGMP, protein kinases, and tyrosine phosphorylation are involved in the nongenomic signalling of progesterone (P4) in sperm. However, it is not known whether there is an interplay between P4 and cannabinoid receptors 1 and 2 (CB1 and CB2), transient receptor potential vanilloid 1 (TRPV1), CatSper channels, cAMP, inositol trisphosphate receptor (IP3R), and mitogen-activated protein kinase (MAPK); these potential regulators are involved in the regulation of capacitation and the acrosome reaction. In the present study, selective blockers of CB1, CB2, TRPV1, CatSper channels, cAMP, protein kinase A (PKA), IP3R, and MAPK were used to identify their involvement in P4-mediated bull sperm capacitation and the acrosome reaction. Selective blocking of any one of the molecules caused a significant reduction in P4 signalling (p < 0.05). Interestingly, blocking these molecules in combination followed by treatment with P4 resulted in the complete absence of capacitation and the acrosome reaction. Blocking a single receptor was not able to eliminate the P4-induced capacitation and the acrosome reaction. In addition to the CB1 and CB2 receptors, there may be other signalling pathways that mediate P4 signalling. In conclusion, P4 signalling exhibited interplay with the cannabinoid receptors. The regulation of sperm capacitation and the acrosome reaction also involved cAMP, PKA, l-type and T-type calcium channels, TRPV1, inositol trisphosphate, and MAPK.

摘要

射精后,精子的转录和翻译能力有限。在输卵管中,大多数精子的信号转导是非基因组的,并通过膜受体介导。研究表明,精子的阳离子通道(CatSper)、cAMP、cGMP、蛋白激酶和酪氨酸磷酸化参与了孕激素(P4)在精子中的非基因组信号转导。然而,目前尚不清楚 P4 是否与大麻素受体 1 和 2(CB1 和 CB2)、瞬时受体电位香草酸 1(TRPV1)、CatSper 通道、cAMP、肌醇三磷酸受体(IP3R)和丝裂原活化蛋白激酶(MAPK)之间存在相互作用;这些潜在的调节剂参与调节顶体反应和精子获能。在本研究中,使用 CB1、CB2、TRPV1、CatSper 通道、cAMP、蛋白激酶 A(PKA)、IP3R 和 MAPK 的选择性阻断剂来鉴定它们在 P4 介导的公牛精子获能和顶体反应中的作用。任何一种分子的选择性阻断都会导致 P4 信号显著减少(p<0.05)。有趣的是,这些分子联合阻断后用 P4 处理会导致完全缺乏获能和顶体反应。阻断单个受体不能消除 P4 诱导的精子获能和顶体反应。除了 CB1 和 CB2 受体外,可能还有其他信号通路介导 P4 信号转导。总之,P4 信号转导与大麻素受体相互作用。精子获能和顶体反应的调节还涉及 cAMP、PKA、L 型和 T 型钙通道、TRPV1、肌醇三磷酸和 MAPK。

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