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Horm Metab Res 2007; 39(6): 474-477
DOI: 10.1055/s-2007-980190
Review

© Georg Thieme Verlag KG Stuttgart · New York

The Role of Corticotropin-releasing Hormone in Blastocyst Implantation and Early Fetal Immunotolerance[*]

S. N. Kalantaridou 1 , E. Zoumakis 2 , A. Makrigiannakis 3 , H. Godoy 4 , G. P. Chrousos 2
  • 1Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Ioannina, Ioannina, Greece
  • 21st Department of Pediatrics, Choremeio Research Laboratory, University of Athens, Athens, Greece
  • 3Department of Obstetrics and Gynecology, Georgetown University Hospital, Washington, DC, USA
  • 4Department of Obstetrics and Gynecology, University of Crete, Heraklion, Greece
Further Information

Publication History

received 23. 11. 2006

accepted 19. 3. 2007

Publication Date:
18 June 2007 (online)

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Abstract

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.

Key words

Endometrial corticotropin-releasing hormone - placental corticotropin-releasing hormone - implantation - maternal tolerance

1 This review is dedicated to the late Alexander Psychoyos, a pioneer in the field of implantation, and a good mentor and friend to many of the authors.

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1 This review is dedicated to the late Alexander Psychoyos, a pioneer in the field of implantation, and a good mentor and friend to many of the authors.

Correspondence

S. N. KalantaridouMD 

Division of Reproductive Endocrinology

Department of Obstetrics and Gynecology

University Hospital of Ioannina Panepistimiou Avenue

45110 Ioannina

Greece

Phone: +30/26/510 99 267

Fax: +30/26/510 97 055

Email: Sophia_kalantaridou@hotmail.com

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