Human Chorionic Gonadotropin: a hormone with immunological and angiogenic properties.

The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological tolerance which allows conceptus survival. A cascade of cytokines mediates this dialogue and is crucial in the cross-talk between the immune and endocrine systems. The first known human embryo-derived signal is chorionic gonadotropin (hCG) by which the embryo profoundly influences immunological tolerance and angiogenesis at the maternal–fetal interface. hCG levels coincide with the development of trophoblast tolerance. Indeed, it increases the number of uterine natural killer cells that play a key role in the establishment of pregnancy. hCG also intervenes in the development of local immune tolerance through the cellular system of apoptosis via Fas/Fas-Ligand. It modulates the Th1/Th2 balance and acts on complement C3 and C4A/B factors modulating decidual immunity. The transient tolerance evident during gestation is at least partially achieved via the presence of regulatory T cells which are attracted by hCG at the fetal–maternal interface. Finally, hCG treatment of activated dendritic cells results in an up-regulation of MHC class II, IL-10 and IDO expression, reducing the ability to stimulate T cell proliferation. Successful implantation requires an extensive endometrial angiogenesis in the implantation site. Recent data demonstrate angiogenic effects of hCG via its interaction with endometrial and endothelial LH/hCG receptors. Our review focuses on these functions of hCG, giving new insight into the endocrine–immune dialogue that exists between the conceptus and immune cells within the receptive endometrium at the time of implantation.