Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish

Taichi Noda, Andreas Blaha, Yoshitaka Fujihara, Krista R. Gert, Chihiro Emori, Victoria E. Deneke, Seiya Oura, Sara Berent, Mayo Kodani, Karin Panser, Luis Enrique Cabrera-Quio, Andrea Pauli, Masahito Ikawa

doi:10.1101/2021.04.18.440256

<jats:title>Abstract</jats:title><jats:p>The process of sperm-egg fusion is critical for successful fertilization, yet the underlying 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<jats:italic>C. elegans</jats:italic>and Sneaky in<jats:italic>D. melanogaster</jats:italic>. Mouse<jats:italic>Dcst1</jats:italic>and<jats:italic>Dcst2</jats:italic>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<jats:italic>dcst1</jats:italic>KO males are subfertile and<jats:italic>dcst2</jats:italic>and<jats:italic>dcst1/2</jats:italic>double KO males are sterile. Zebrafish<jats:italic>dcst1/2</jats:italic>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.</jats:p>

Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish

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