Participation of maternal and fetal CRH in early phases of human implantation: the role of antalarmin.

Abstract

The hypothalamic neuropeptide corticotropin-releasing hormone (CRH) is produced by several tissues of the female reproductive system. It is also secreted at inflammatory sites and possesses potent pro-inflammatory properties influencing both innate and acquired immune processes. Uterine CRH participates in local immune early pregnancy phenomena, such as decidualization of endometrial strom a and protection of the fetus from maternal immune system. This is maintained through induction of the expression of apoptotic FasL on invasive extravillous trophoblast and maternal decidual cells at the fetal-maternal interface. Furthermore, CRH increases apoptosis of activated T lymphocytes through FasL induction participating in the process of implantation and early pregnancy. Female rats treated with the non-peptidic CRH receptor 1 (CRHR1) specific antagonist antalarmin, in the first 6 days of gestation, have undergone a decrease of endometrial implantation sites and live embryos and markedly diminished endometrial FasL expression.