Participation Of 'Crisp' Proteins In Gamete Interaction And Their Potential Use For Male Fertility Regulation

摘要

Epididymal protein CRISP 1, 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 CRISP 1 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 CRISP 1 "knock out" animals showed that, despite a normal animal fertility, CRISP 1-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 CRISP 1 raises specific antibodies which inhibits not only sperm fertilizing ability but also animal fertility, supports CRISP 1 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.