Studies of sperm from mutant mice suggesting that two neurotransmitter receptors are important to the zona pellucida-initiated acrosome reaction.

Studies of sperm from mutant mice suggesting that two neurotransmitter receptors are important to the zona pellucida-initiated acrosome reaction.
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对突变小鼠精子的研究表明,两种神经递质受体对于透明带引发的顶体反应很重要。

DOI:
10.1002/mrd.20336
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发表时间:
2005
期刊:
Molecular reproduction and development.
影响因子:
--
通讯作者:
Son,Jung-Ho
Son,Jung-Ho
中科院分区:
--
文献类型:
--
作者:
Meizel,Stanley;Son,Jung-Ho

文献摘要

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Two sperm neurotransmitter receptor/channels, the glycine receptor (GlyR) and a nicotinic acetylcholine receptor containing an α7 subunit (α7nAChR) were previously shown to be important to the mouse acrosome reaction (AR) initiated by solubilized egg zona pellucida (ZP). Here, we investigated whether sperm from homozygous mutant mice with a single amino acid mutation in the α subunit of their GlyR and sperm from homozygous mutant mice with an engineered disruption of the gene for the nicotinic acetylcholine receptor α7 subunit could undergo the AR on ZP‐intact eggs. Wild‐type and mutant sperm were treated with 3‐quinuclidinyl benzilate (QNB), known to be an inhibitor of the ZP‐initiated AR (but shown in the present work not to inhibit the acetylcholine‐initiated AR). The ZP‐initiated AR on ZP‐intact eggs should occur only in sperm not treated with QNB. The absence of such an increase in the untreated mutant sperm would demonstrate that such sperm were unable to respond to the intact ZP. The results demonstrated for the first time that GlyR mutant sperm do not undergo the AR on ZP‐intact mouse eggs, and that their ability to fertilize is inhibited by 63% in vitro. Moreover, we found that GlyR mutant sperm exhibited normal capacitation and confirmed that they not undergo the AR initiated by solubilized mouse ZP. Our studies demonstrated for the first time that sperm from mutant α7nAChR mice exhibit normal capacitation, do not undergo the AR in response to acetylcholine, solubilized ZP or on ZP‐intact eggs, and display a 25% reduction in fertilization in vitro. This is the first genetic evidence for the importance of the α7nAChR in the ZP‐initiated AR. While defects in either the GlyR or the α7nAChR completely inhibit the ZP‐initiated AR, fertilization by these mutant sperm can still occur in vitro, probably due to sperm that complete spontaneous AR on the ZP. © 2005 Wiley‐Liss, Inc.