Immune cells contribute to systemic cross-talk between the embryo and mother during early pregnancy in cooperation with the endocrine system

In early pregnancy, human chorionic gonadotropin (HCG) stimulates the corpus luteum to produce progesterone that in turn maintains human embryo implantation in the uterus. This inevitable communication through blood circulation can be called 'systemic cross-talk between the embryo and mother'. Despite considerable evidence suggesting that the human corpus luteum cannot be maintained by HCG alone, no other responsible soluble factors have been proposed. We found that peripheral blood mononuclear cells (PBMC) derived from pregnant women promoted progesterone production by human luteal cells and propose that both hormones and immune cells participate in this systemic cross-talk. This systemic cross-talk by immune cells is believed to operate in embryo implantation. Splenocytes derived from pregnant mice promoted endometrial differentiation and embryo implantation in vivo . Human PBMC derived from women early in pregnancy promoted invasion of murine embryos in vitro. In addition, recombinant HCG increased the effects of human PBMC on murine embryo invasion. Human chorionic gonadotropin also increased chemokine production by human PBMC through a lectin–glycan interaction, which is a primitive pathway in the immune system. Furthermore, chemokines were shown to induce human trophoblast invasion. These findings suggest that the immune system positively contributes to systemic cross-talk between the embryo and mother in cooperation with the endocrine system. (Reprod Med Biol 2006; 5 : 19–29)