Inhibition of human spermatozoon--oocyte interaction in vitro by monoclonal antibodies to CD46 (membrane cofactor protein)

CD46 (membrane cofactor protein) is a cell surface complementregulatory glycoprotein that facilitates enzymatic cleavageof complement component C3b; it is expressed by both human oocytesand acrosome-reacted spermatozoa. Murine anti-CD46 monoclonalantibody (mAb) has been reported to decrease significantly theability of human spermatozoa to penetrate hamster oocytes. Wehave investigated the effect of purified anti-CD46 mAbs on spermatozoon-oocyteinteraction in an autologous zona-free oocyte penetration test.Oocytes and/or spermatozoa were preincubated with either oftwo anti-CD46 murine mAbs, TRA.2.10 (a non-blocking mAb) andMH61 (a mAb that functionally blocks C3b-ligand binding activity),or a control isotype-matched mAb, in medium supplemented withhuman serum albumin. Preincubation of both spermatozoa and zona-freeoocytes with TRA.2.10, but not MH61, caused a significant decreasein the number of oocytes showing sperm binding and pronuclearformation (9/23) compared with controls (21/26) in this complementcomponent-depleted medium. This effect was not observed if oocytesor spermatozoa alone were preincubated. These data suggest thatCD46 has a role in human spermatozoon-oocyte interaction atthe level of the ooocyte plasma membrane, and indicate thata novel function other than direct C3b binding could be involved.