Relevance of CRISP proteins for fertilization and fertility

CUASNICÚ PS

Miami

Conferencia; ASA 43rd Annual Conference; 2017

American Society of Andrology

Fertilization is a key process involving a series ofcoordinated interactions between the gametes. However, the mechanismsunderlying this process still remain to be elucidated. Ourlaboratory has been dedicated to underpin the molecular mechanisms involved in boththe acquisition of sperm fertilizing ability during maturation andfertilization using CRISP proteins as model molecules. Epididymalprotein CRISP1, the first described member of the evolutionarily conservedCRISP (Cystein-Rich Secretory Protein) family,associates with the sperm surface during maturation. Whereas the loosely boundCRISP1 is released during capacitation having been proposed as a decapacitatingfactor, substantial evidence obtained using in vitro assays and knockout (KO) modelsshows that the strongly bound population still present in capacitated sperm participatesin different stages of fertilization. These observations can be extended tohuman as our findings show that the human homologue of CRISP1 (hCRISP1) alsoassociates with sperm during maturation and participates in fertilization. Recentobservations revealed that CRISP1 is also expressed by the cumulus cells thatsurround the egg and participates in fertilization by modulating sperm orientation and hyperactivation through itsability to regulate CatSper, a key sperm Ca(2+) channel essential for male fertility.In spite of these important roles, KO mice for CRISP1 are fertile in the sameway as mice lacking CRISP4, another epididymal CRISP protein involved infertilization. Interestingly, recent evidence shows that, in addition to the lowerfertilization rates observed in KO mice for each individual CRISP protein, the doubleCRISP1/CRISP4 KO males exhibited a significant decrease in fertility as well assevered defects at the epididymal level with abnormal presence of immune cellswithin the tissue. Together, these observations confirmed the relevance ofCRISP proteins for fertility and revealed novel inmunoregulatory roles for theseproteins within the epididymis. We believe these results provideimportant information for a better mechanistic understanding of bothepididymal maturation and fertilization and will contribute to futureresearch on infertility and contraception.