The role of corticotropin-releasing hormone in blastocyst implantation and early fetal immunotolerance.
During blastocyst implantation, the maternal endometrial response to the invading semi-allograft has characteristics of an acute, aseptic inflammatory response. However, once implanted, the embryo suppresses this response and prevents rejection. Simultaneously, the mother's immune system prevents a graft VS. host reaction deriving from the fetal immune system. We have shown that embryonic trophoblast and maternal decidua cells, i.e., cells located in the interface between the fetal placenta and the maternal endometrium, produce corticotropin-releasing hormone (CRH) and express Fas ligand. CRH may play a crucial role in the implantation and the anti-rejection process that protects the fetus from the maternal immune system, primarily by killing activated T cells through the Fas-FasL interaction. In experimental animals, type 1 CRH receptor (CRH-R1) blockade by antalarmin, a specific type 1 CRH receptor antagonist, decreased implantation sites by approximately 70%. CRH is also involved in controlled trophoblast invasion, by downregulating the synthesis of the carcinoembryonic antigen-related cell adhesion molecule 1 by extravillous trophoblast cells. IN VITRO findings showed that CRH-R1 blockade by antalarmin increased trophoblast invasion by approximately 60%. Defective uterine CRH/CRH-R1 system during early pregnancy may be implicated in the pathophysiology of recurrent miscarriage, placenta accreta, and preeclampsia.
Kalantaridou
S N
SN
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Ioannina, Ioannina, Greece. Sophia_kalantaridou@hotmail.com
Zoumakis
E
E
Makrigiannakis
A
A
Godoy
H
H
Chrousos
G P
GP
D002454:Cell Differentiation; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D003656:Decidua / Q000166:cytology; D010064:Embryo Implantation / Q000276:immunology*; D005260:Female; D005298:Fertility; D005333:Fetus / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D011247:Pregnancy; D017154:Stromal Cells / Q000166:cytology
D003346:Corticotropin-Releasing Hormone