CRISP1 as a novel CatSper regulator that modulates sperm motility and orientation during fertilization

CARVAJAL G; DE LA VEGA-BELTRAN JL; M. WEIGEL MUÑOZ; CUASNICU P S; DULCE FIGUEIRAS-FIERRO; COHEN D. J.; LUDMILA CURCI; GERARDO ORTA; ALBERTO DARSZON

Seminario; The Betsheva de Rotschild Seminar on Challanges and Frontiers in Mammalian Reproduction; 2016

Evidence from our laboratory indicates that CRISP1, a sperm protein involved in mammalian fertilization, is also present in the female gamete and modulates key sperm Ca2+ channels. More specifically, we observed that CRISP1 is expressed by the cumulus cells that surround the egg and that fertilization of cumulus?oocyte complexes from CRISP1 knockout females is impaired because of a failure of sperm to penetrate the cumulus. We provided evidence indicating that CRISP1 stimulates sperm orientation, modulates sperm hyperactivation and regulates CatSper, the principal sperm Ca2+ channel involved in hyperactivation and essential for fertility. Given the critical role of Ca2+ for sperm motility, we proposed that cumulus CRISP1 mediates a novel fine-tuning mechanism that regulates sperm orientation by modulating hyperactivation through its ability to regulate CatSper. This proposed mechanism is supported by recent results showing the impact of different calcium regulators on sperm orientation. Moreover, recent in vivo studies showed a significantly lower percentage of fertilized eggs within the ampulla of CRISP1 knockout than control females after natural mating, supporting the functional relevance of cumulus CRISP1 for fertilization.