Department of Cell Biology and Histology, Medical School, University of Murcia, IMIB-Arrixaca, Murcia, Spain
Enrica Bianchi
Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom
Beatriz Fernández-Fuertes
School of Agriculture and Food Science, University College Dublin, Dublin, Ireland; Department of Biology, Faculty of Sciences, Institute of Food and Agricultural Technology, University of Girona, Girona, Spain
The fusion of gamete membranes during fertilization is an essential process for sexual reproduction. Despite its importance, only three proteins are known to be indispensable for sperm-egg membrane fusion: the sperm proteins IZUMO1 and SPACA6, and the egg protein JUNO. Here we demonstrate that another sperm protein, TMEM95, is necessary for sperm-egg interaction. TMEM95 ablation in mice caused complete male-specific infertility. Sperm lacking this protein were morphologically normal exhibited normal motility, and could penetrate the zona pellucida and bind to the oolemma. However, once bound to the oolemma, TMEM95-deficient sperm were unable to fuse with the egg membrane or penetrate into the ooplasm, and fertilization could only be achieved by mechanical injection of one sperm into the ooplasm, thereby bypassing membrane fusion. These data demonstrate that TMEM95 is essential for mammalian fertilization.