Monoclonal antibody c262 counteracts the stimulatory effect of progesterone on sperm-oocyte fusion

Some evidence suggests that the non-genomic effects exerted by progesterone (P) on human spermatozoa are mediated by membrane receptor(s) displaying the C-terminal domain, but not the N-terminal domain of the genomic P receptor (PR). This study aimed at determining whether the monoclonal antibody (mAb) c-262, directed against the C-terminal domain of the genomic PR, counteracts the stimulatory effect of P on the human sperm ability to fuse with oocytes. Sperm/oocyte fusion was evaluated by means of the hamster egg penetration test. The brief exposure of capacitated spermatozoa to P produced a stimulatory effect on sperm/oocyte fusion. mAb c262 counteracted this stimulatory effect in a dose-dependent manner. No counteraction was observed when capacitated spermatozoa were pre-exposed to PGR-312, a mAb directed against the N-terminal domain of the genomic PR. These results reinforce the hypothesis that the non-genomic effects exerted by P on human spermatozoa are mediated by membrane receptor(s) displaying the C-terminal domain, but not the N-terminal domain of the genomic PR.