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

ERNESTO JI #; WEIGEL MUÑOZ M #; BATTISTONE M. A.,; VASEN G; MARTÍNEZ-LÓPEZ, P; GERARDO ORTA; DULCE FIGUEIRAS-FIERRO; DE LA VEGA-BELTRAN JL; MORENO I,; ALEJANDRO GUIDOBALDI; LUDMILA CURCI; CARVAJAL G; GIOJALAS L; ALBERTO DARSZON; COHEN D. J.; CUASNICU P S

boston

Congreso; Gordon Research Conference Fertilization & Activation of Development; 2015

Calcium-dependent mechanisms are critical for successful completion of fertilization. Here, we demonstrate that CRISP1, a sperm protein involved in mammalian fertilization, is also present in the female gamete and capable of modulating key sperm Ca2+ channels. Specifically, we show 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 due to a failure of sperm to penetrate the cumulus. We provide evidence that CRISP1 stimulates sperm orientation by modulating sperm hyperactivation, a vigorous motility required for penetration of the egg vestments. Moreover, patch-clamping of sperm revealed that CRISP1 has the ability to regulate CatSper, the principal sperm Ca2+ channel involved in hyperactivation and essential for fertility. Given the critical role of Ca2+ for sperm motility, we propose a novel CRISP1-mediated fine-tuning mechanism to regulate sperm hyperactivation and orientation for successful penetration of the cumulus during fertilization.