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

Abstract

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+ forsperm motility, we propose a novel CRISP1-mediated fine-tuning mechanism to regulatesperm hyperactivation and orientation for successful penetration of the cumulus during fertilization.