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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/C17    most recent 00013.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Cavanagh, P. C. Articles by Babwah, A. V. PubMed PubMed Citation Articles by Cavanagh, P. C. Articles by Babwah, A. V.

RECEPTORS AND SIGNAL TRANSDUCTION

Gonadotropin-releasing hormone-regulated chemokine expression in human placentation

¹The Children's Health Research Institute, ²Lawson Health Research Institute, ³Department of Obstetrics and Gynaecology, ⁴Department of Physiology and Pharmacology, ⁵Department of Anatomy and Cell Biology, and ⁶Department of Pediatrics, The University of Western Ontario, London, Ontario; ⁷Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto; and ⁸Department of Physiology and ⁹Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada

Submitted 12 January 2009 ; accepted in final form 9 April 2009

Placental expression of gonadotropin-releasing hormone (GnRH)-I and II, as well as their cognate receptor, coincides with a period of extensive remodeling of the maternal-fetal interface, near the end of the first trimester of pregnancy. To further define the role of GnRH in human placentation, we performed a microarray screen of HTR-8/SVneo trophoblasts to identify GnRH-regulated genes and their roles in placentation. This screen revealed that GnRH regulates the expression of four angiogenic chemokines: CXCL2, CXCL3, CXCL6, and CXCL8. The microarray data were subsequently confirmed by an extensive Q-PCR time-course analysis. CXCL8, a representative chemokine, was selected for further analysis and shown to be strongly expressed by trophoblasts at the maternal-fetal interface of the human placenta, as well as to accumulate in a GnRH-dependent manner in trophoblast-conditioned media in culture. Trophoblasts were subsequently shown to recruit lymphocytes (Jurkat T cells and primary peripheral blood T and uterine natural killer cells) in chemotaxis assays and this was shown to be GnRH dependent. Furthermore, this recruitment was shown to occur via the release of CXCR1/CXCR2 interacting chemokines, such as the CXCLs investigated in this study. This novel regulation of chemokines by GnRH signaling demonstrates the role of GnRH in regulating the recruitment of lymphocytes to the decidua and the possibility of a direct effect on spiral artery remodeling via the release of proangiogenic chemokines and secondary effects via release of angiogenic factors by recruited lymphocytes.

angiogenic chemokine; extravillous trophoblast; placenta

This article has been cited by other articles:

				W. J. Pearce Multifunctional angiogenic factors: add GnRH to the list. Focus on "Gonadotropin-releasing hormone-regulated chemokine expression in human placentation" Am J Physiol Cell Physiol, July 1, 2009; 297(1): C4 - C5. [Full Text] [PDF]