Sperm IZUMO1 Is Required for Binding Preceding Fusion With Oolemma in Mice and Rats.

Sperm IZUMO1 Is Required for Binding Preceding Fusion With Oolemma in Mice and Rats.
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DOI:
10.3389/fcell.2021.810118
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发表时间:
2021
影响因子:
5.5
通讯作者:
Ikawa M
Ikawa M
中科院分区:
生物学2区
文献类型:
--
作者:
Matsumura T;Noda T;Satouh Y;Morohoshi A;Yuri S;Ogawa M;Lu Y;Isotani A;Ikawa M

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受精是多步骤复杂过程的最终结果。首先,哺乳动物精子经历顶体反应以具有融合能力。然后,顶体反应的精子穿透透明带并粘附并最终与卵质膜融合。 IZUMO1 是第一个被证明对哺乳动物精卵融合至关重要的精子蛋白,因为 Izumo1 敲除小鼠的精子会粘附在卵膜上,但无法与卵膜融合。然而,IZUMO1 在其他物种中的功能仍然很大程度上未知。在这里,我们通过 CRISPR/Cas9 培育了 Izumo1 敲除大鼠,发现雄性大鼠不育。与小鼠不同,Izumo1 基因敲除的大鼠精子未能与卵膜结合。进一步的研究表明,在 Izumo1 敲除小鼠中,顶体完整精子的结合掩盖了与卵膜结合的顶体反应精子数量的减少。值得注意的是,在缺乏最近发现的融合必需基因 Fimp、Sof1、Spaca6 或 Tmem95 的小鼠中,我们在顶体反应的精子与卵膜的结合中没有看到任何明显的缺陷。总的来说,我们的数据表明,至少在大鼠中,IZUMO1 是融合前精子-卵膜结合所必需的。
Fertilization occurs as the culmination of multi-step complex processes. First, mammalian spermatozoa undergo the acrosome reaction to become fusion-competent. Then, the acrosome-reacted spermatozoa penetrate the zona pellucida and adhere to and finally fuse with the egg plasma membrane. IZUMO1 is the first sperm protein proven to be essential for sperm-egg fusion in mammals, as Izumo1 knockout mouse spermatozoa adhere to but fail to fuse with the oolemma. However, the IZUMO1 function in other species remains largely unknown. Here, we generated Izumo1 knockout rats by CRISPR/Cas9 and found the male rats were infertile. Unlike in mice, Izumo1 knockout rat spermatozoa failed to bind to the oolemma. Further investigation revealed that the acrosome-intact sperm binding conceals a decreased number of the acrosome-reacted sperm bound to the oolemma in Izumo1 knockout mice. Of note, we could not see any apparent defects in the binding of the acrosome-reacted sperm to the oolemma in the mice lacking recently found fusion-indispensable genes, Fimp, Sof1, Spaca6, or Tmem95. Collectively, our data suggest that IZUMO1 is required for the sperm-oolemma binding prior to fusion at least in rat.
DOI: 10.1038/nature18595
发表时间: 2016-06-23
期刊: Nature
影响因子: 64.8
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