From fertilization to the immune system

CUASNICÚ PS

Barranquilla

Congreso; XIX Reunión Anual de la Sociedad Argentina de Biología (SAB). Reunión Conjunta de Sociedades de Biociencias; 2017

Fertilization is a key process involving a series ofcoordinated interactions between the male and female gametes. However, themechanisms underlying this key process still remain to be elucidated. Ourlaboratory has been dedicated to underpin the molecular mechanisms involved inthe acquisition of sperm fertilizing ability and gamete interaction using CRISPproteins as model molecules. Epididymal protein CRISP1,the first described member of the evolutionarily conserved CRISP (Cystein-RichSecretory Protein) family, associates with the sperm surfaceduring the maturation process that occurs while passing through the epididymis.Substantial evidence obtained using in vivoand in vitro approaches as well as knockout(KO) models shows that CRISP1 participates in both sperm-egg binding and gametefusion through its interaction with egg-complementary sites. These observationscan be extended to human as judged by the finding that the human CRISP1 alsoassociates with sperm during maturation and participates in fertilizationthrough binding sites in the human egg.  More recent results reveal that CRISP1 is anovel regulator of CatSper, the principal sperm Ca(2+) channel essential for male fertility and thatthe protein is also expressed by the cumulus cells that surround the egg actingas a sperm chemoatractant during cumulus penetration. Thus, CRISP1 escorts boththe male and female gamete and plays multiple roles during the fertilizationprocess. In spite of its functional relevance, CRISP1 KO miceare fertile as are mice lacking CRISP4, another epididymal CRISP family memberalso involved in fertilization. Interestingly, recent evidence from our group showsthat the simultaneous lack of both CRISP1 and CRISP4 (double KO) affects notonly fertilization but also male fertility, confirming the existence ofcompensatory mechanisms between homologue proteins to ensure reproductivesuccess. Moreover, the double KO males show severe defects in both the epididymalepithelium and luminal sperm as well as an abnormal presence of immune cellswithin the organ indicative of a disruption of the characteristic immunetolerance of the epididymis. Together, these observations confirm the relevanceof CRISP proteins for fertilization and fertility and reveal novelinmunoregulatory roles for these proteins within the epididymis. Webelieve these results provide important information for a better mechanisticunderstanding of the maturation and fertilization processes that willcontribute to future research on infertility and contraception.