Gamete proteins involved in mammalian fertilization: tools for fertility regulation?

VAZQUEZ-LEVIN, MÓNICA; VEAUTE, CAROLINA; MARIN-BRIGGILER, CLARA

Boston

Congreso; Building bridges in reproductive immunology - ISIR 2013; 2013

International Society for Reproductive Immunology

Fertilization is a complex process that involves a set ofcoordinated interactions between the spermatozoa andthe oocyte. Spermatozoa are produced in the testis andundergo maturation during epididymal transit. Onceejaculated, they are transported in the female tract,where they develop full fertilizing competence in aprocess called capacitation, by means of their interactionwith the oviductal epithelium and its secretions.Upon arrival to the fertilization site, capacitated spermatozoa interact with the cumulus cells and the unfertilized egg-extracellular coat, the zona pellucida (ZP), and undergo acrosomal exocitosis (AE); this process involves the release of acrosomal contents, mainly proteases, and the exposure of the inner acrosomal membrane. Spermatozoa that have completed AE and ZP penetration, reach the perivitelline space, bind and fuse to the oolema. The identification of sperm and oocyte proteins that participate in fertilization-related events has been the subject of numerous investigations aimed at unraveling the molecular basis of fertilization, to improving diagnosis and treatment of infertility, and developing strategies to regulate fertility. As part of these studies, much interest has been paid in the study of natural occurring Anti Sperm Antibodies (ASA) and their impact in fertility, because their presence of in the male and/or female partner has been associated to 2? 50% of human infertility cases and a reduced probability of achieving a spontaneous pregnancy. ASA have found to impair some fertilization steps, i.e. sperm transport within the female genital tract, sperm capacitation, AE, gamete interaction, implantation and early embryonic development. Based on these observations, several sperm proteins have been used as immunogens in the development of animal models to identify their involvement in fertilization-related events and the ability of their antibodies to modulate fertility. In addition to sperm proteins, other molecules have been used in these studies, among them ZP glycoproteins. Our team has developed several research lines to evaluate natural ASA in body fluids as well as to assess their impact on fertilization. In addition, we have used antibodies towards specific gamete components to characterize their site of synthesis in the reproductive tract, their expression/localization and their involvement in fertilization. Our studies have been done in human, murine and bovine models. Among them we have identified ASA in sera and follicular fluid from infertile patients, and assessed their impact in sperm performance (AE, in vitro fertilization). We have described the incidence of antibodies towards the sperm acrosomal proacrosin/ acrosin system in sera from infertile, by implementing a sensitive ELISA assay and we have evaluated the potential impact in fertility by developing in vitro assays and a gene immunization murine model. We have used blocking antibodies to cell-cell adhesion molecules from the cadherin superfamily to evaluate their involvement infertilization. These studies characterized the expression of Epithelial and Neural cadherin in the reproductive tract, their localization in both gametes and their involvement in sperm-oocyte adhesion events during gamete recognition. Natural and acquired antisperm antibodies towards gamete proteins used as tools for fertility-regulation remain a powerfultool towards the understanding of fertilization and the relevance of immunological infertility.