National Academy of Sciences, Proceedings of the National Academy of Sciences, 21(117), p. 11493-11502, 2020
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Significance The sperm−oocyte fusion step is important to transport the male genome into oocytes. So far, IZUMO1 and FIMP have been identified as fusion-related proteins in spermatozoa, but the molecular mechanisms underpinning sperm−oocyte fusion and all of the proteins required for this essential process remain unclear. In this study, using CRISPR-Cas9−mediated gene knockouts in mice, we discover that sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm−oocyte fusion and male fertility. As these genes are conserved among mammals including human, they may explain not only the sperm−oocyte fusion process but also idiopathic male infertility and be unique targets for contraception.