Regulation of the complement system in reproduction is unique inasmuch as reproductive tissues represent the only condition where allogeneic interactions occur naturally. Both allogeneic extraembryonic membranes and semen that contact and interact with maternal cells and tissues must avert complement‐mediated damage to ensure reproductive success. Several regulators of complement activation exist. Membrane cofactor protein (MCP) and decay accelerating factor (DAF) inactivate C3 and C5 convertases on cell surfaces. In addition, CD59 inhibits the membrane attack complex (MAC) of the complement cascade. Strong expression of these membrane glycoproteins by trophoblast and amniotic epithelium has been observed. MCP, DAF, and CD59 likely safeguard extraembryonic tissues from complement damage originating from maternal and fetal blood or amniotic fluid.

Different reproductive tract fluids vary in complement levels. With the exception of ovarian follicular fluid, these levels are generally much less than those in blood. Endometrial and cervical content of C3 appear to be regulated by hormones. These observations suggest that the effects of complement activation may vary in reproductive tissues. MCP is absent from the surfaces of oocytes. Sperm express MCP and DAF in discrete areas that would not be associated with the known complement‐regulatory functions of these proteins. Seminal plasma contains MCP and the MAC inhibitor SP‐40,40 but not DAF. SP‐40,40 may exemplify how complement‐regulatory proteins perform alternative functions as it interacts with molecules other than complement components. We have reviewed aspects of the complement system that relate to allogeneic interactions in reproduction and that suggest fruitful areas for further research.