“Participation of “CRISP” proteins in gamete interaction and their potential use for male fertility regulation.”

COHEN DJ; MALDERA JA; WEIGEL MUÑOZ M; ERNESTO JI; GOLDEWEIC NM; CUASNICU PS

Papers contributed to the 9th International Congress of Andrology

Medimond International Proceedings

Lugar: Bologna, Italia; Año: 2009; p. 25 - 28

Epididymal protein CRISP1, a member of the Cysteine-RIch Secretory Protein (CRISP) family, was identified by our laboratory and postulated to participate in gamete fusion by binding to egg-complementary sites. Structure-function studies revealed that its egg-binding ability resides in a 12 amino acid region corresponding to an evolutionary conserved motif of the CRISP family, named Signature 2 (S2). In addition to this, recent results revealed that CRISP1 would also be involved in the previous step of sperm binding to the zona pellucida (ZP), identifying a novel role for this protein in fertilization. The generation of CRISP1 “knock out” animals showed that, despite a normal animal fertility, CRISP1-defficient sperm present an impaired ability to fertilize both zona-intact and zona-free eggs confirming the proposed roles of the protein in gamete interaction. The finding that immunization of rats with native or recombinant CRISP1 raises specific antibodies which inhibits not only sperm fertilizing ability but also animal fertility, supports CRISP1 as a good epididymal contraceptive target. Evidence indicated that human CRISP1 (hCRISP1), as its rodent counterpart, also participates in both gamete fusion and sperm-ZP binding. The relevance of hCRISP1 for human fertility is currently being investigated in our laboratory by immunization studies in a non-human primate model. Altogether, these results increase our understanding on the molecular mechanisms of gamete interaction and support the potential use of CRISP family members for the development of new and safer fertility regulating methods.