PT - JOURNAL ARTICLE AU - Taichi Noda AU - Andreas Blaha AU - Yoshitaka Fujihara AU - Krista R. Gert AU - Chihiro Emori AU - Victoria E. Deneke AU - Seiya Oura AU - Sara Berent AU - Mayo Kodani AU - Karin Panser AU - Luis Enrique Cabrera-Quio AU - Andrea Pauli AU - Masahito Ikawa TI - Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish AID - 10.1101/2021.04.18.440256 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.04.18.440256 4099 - http://biorxiv.org/content/early/2021/04/18/2021.04.18.440256.short 4100 - http://biorxiv.org/content/early/2021/04/18/2021.04.18.440256.full AB - The process of sperm-egg fusion is critical for successful fertilization, yet the underpinning mechanisms that regulate these steps have remained unclear in vertebrates. Here, we show that both mouse and zebrafish DCST1 and DCST2 are necessary in sperm to fertilize the egg, similar to their orthologs SPE-42 and SPE-49 in C. elegans and Sneaky in D. melanogaster. Mouse Dcst1 and Dcst2 single knockout (KO) spermatozoa are able to undergo the acrosome reaction and show normal relocalization of IZUMO1, an essential factor for sperm-egg fusion, to the equatorial segment. While both single KO spermatozoa can bind to the oolemma, they rarely fuse with oocytes, resulting in male sterility. Similar to mice, zebrafish dcst1 KO males are subfertile and dcst2 and dcst1/2 double KO males are sterile. Zebrafish dcst1/2 KO spermatozoa are motile and can approach the egg, but rarely bind to the oolemma. These data demonstrate that DCST1/2 are essential for male fertility in two vertebrate species highlighting their crucial role as conserved factors in fertilization.Competing Interest StatementThe authors have declared no competing interest.