LYPD4, mouse homolog of a human acrosome protein, is essential for sperm fertilizing ability and male fertility
LYPD4, mouse homolog of a human acrosome protein, is essential for sperm fertilizing ability and male fertility
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LYPD4 是人类顶体蛋白的小鼠同源物，对于精子受精能力和男性生育能力至关重要
DOI：
10.1093/biolre/ioaa018
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发表时间：
2020
影响因子：
3.6
通讯作者：
Xu Eugene Yujun
中科院分区：
文献类型：
--
作者：
Wang Dan;Cheng Liping;Xia Wenjuan;Liu Xiaofei;Guo Yueshuai;Yang Xiaoyu;Guo Xuejiang;Xu Eugene Yujun
受精是一个基本的生物学过程，但到目前为止，我们仍然没有完全了解其分子机制。我们已经确定了一个人类顶体蛋白，LY 6/PLAUR域包含4（LYPD 4），在人类睾丸和精子中特异性表达，并在哺乳动物中保守。MouseLypd 4也特异于睾丸和精子，对男性生育力至关重要。LYPD 4蛋白首先出现在圆形精子细胞顶体生物发生过程中，在精子发生过程中和成熟精子中成为顶体的一部分。然而，突变精子在雌性生殖道内的精子迁移过程中未能到达输卵管，导致受精失败和不育。此外，Lypd 4突变精子不能通过IVF（体外受精）使裸露的卵子受精，但可以使完整的卵丘-卵母细胞复合体中的卵子受精，这支持了精子-卵母细胞相互作用的额外作用。在通过质谱分析鉴定的5000多个精子蛋白质中，只有一小部分蛋白质（26个蛋白质）在不存在LYPD 4的情况下发生了变化，揭示了精子迁移和精子结合缺陷的突变精子的整个蛋白质组图。受精复合体的关键成分ADAM 3以及其他精子ADAM蛋白显著减少。因此，我们认为LYPD 4在哺乳动物受精中起着至关重要的作用，进一步研究其功能及其与其他精子膜复合物的相互作用可能会深入了解人类受精和提高IVF成功率的新策略。
Fertilization is one of the fundamental biological processes, but so far, we still do not have a full understanding of the underlying molecular mechanism. We have identified a human acrosome protein, LY6/PLAUR domain containing 4 (LYPD4), expressed specifically in human testes and sperm, and conserved within mammals. MouseLypd4,also specific to the testis and sperm, is essential for male fertility. LYPD4 protein first appeared in round spermatids during acrosome biogenesis and became part of acrosomes during spermatogenesis and in mature sperm.Lypd4knockout mice are infertile with normal sperm number and motility. Mutant sperm, however, failed to reach oviduct during sperm migration inside the female reproductive tract, leading to fertilization failure and infertility. In addition,Lypd4mutant sperms were unable to fertilize denuded egg via IVF (in vitro fertilization) but could fertilize eggs within intact Cumulus-Oocyte Complex, supporting an additional role in sperm-zona interaction. Out of more than five thousand spermatozoa proteins identified by mass spectrometry analysis, only a small subset of proteins (26 proteins) was changed in the absence of LYPD4, revealing a whole proteome picture of mutant sperm defective in sperm migration and sperm-zona binding. ADAM3, a key component of fertilization complex, as well as other sperm ADAM proteins are significantly reduced. We hence propose that LYPD4 plays an essential role in mammalian fertilization, and further investigation of its function and its interaction with other sperm membrane complexes may yield insights into human fertilization and novel strategy to improve IVF success.