Corticotropin-releasing hormone promotes blastocyst implantation and earlymaternal tolerance

The semi-allograft embryo in the blastocyst stage implants itself in the en dometrium, yet no immune rejection processes are activated. Embryonic troph oblast and maternal decidua produce corticotropin-releasing hormone (CRH) a nd express Fas ligand (FasL), a proapoptotic cytokine. We found that antala rmin, a CRH receptor type I antagonist, decreased FasL expression and promo ted apoptosis of activated T lymphocytes, an effect which was potentiated b y CRH and inhibited by antalarmin. Female rats treated with antalarmin show ed a marked decrease in implantation sites and live embryos and diminished endometrial FasL expression. Embryos from mothers that lacked T cells or fr om syngeneic matings were not rejected when the mothers were given antalarm in. These findings suggested that locally produced CRH promotes implantatio n and maintenance of early pregnancy primarily by killing activated T cells .