Immune function in pregnancy: the role of corticotropin-releasing hormone

Pregnancy represents a major challenge to the maternal immune system since it has to tolerate the semi-allograft fetus. Indeed, the success of pregnancy requires an appropriate immunological interaction between the mother and the fetus. Furthermore, evidence suggests that some pregnancy complications, such as spontaneous abortions, preeclampsia and intrauterine growth restriction, are associated with abnormal maternal-fetal immune responses. Corticotropin-releasing hormone (CRH), a 41-amino acid peptide originally found in the hypothalamus, appears to have a fundamental role in the mechanisms responsible for the implantation and maintenance of human pregnancy. Reproductive CRH is a form of tissue CRH (CRH found in peripheral tissues), analogous to the immune CRH detected in peripheral inflammatory sites. Reproductive CRH has been identified in the endometrial glands, the decidualized endometrial stroma and the placental trophoblast, synctiotrophoblast and decidua. Reproductive CRH participates in various reproductive functions with an inflammatory component, where it serves as an autocrine/paracrine modulator. The immunological mechanisms contributing to the establishment and maintenance of pregnancy are not fully understood. The present article focuses on the potential roles of CRH on the physiology and pathophysiology of pregnancy and highlights its participation in implantation, early fetal immunotolerance and parturition.