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Cellular Localization of Gonadotropin-Releasing Hormone (GnRH) I and GnRH II in First-Trimester Human Placenta and Decidua

Department of Obstetrics and Gynecology (A.G.B., C.D.M., P.C.K.L.), University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5; and Department of Obstetrics and Gynecology (C.-S.C.), Taipei Medical University, Taipei, Taiwan, Republic of China

Address all correspondence and requests for reprints to: Peter C. K. Leung, Ph.D., Department of Obstetrics and Gynecology, University of British Columbia, Room 2H-30, 4490 Oak Street, Vancouver, British Columbia, Canada V6H 3V5. E-mail:peleung{at}interchange.ubc.ca.

There is increasing evidence to suggest that the classical form of GnRH (GnRH I) and the second mammalian form of this hormone, GnRH II, play regulatory roles in human implantation and placentation. To date, the cellular distribution of these two hormones at the maternal-fetal interface remains poorly characterized. In these studies, we localized GnRH I and GnRH II expression in human placenta and decidua to distinct subpopulations of cells isolated from these tissues and in a chorionic villous/decidual tissue coculture system that mimics many of the cellular events of early placentation. GnRH I and GnRH II mRNA transcripts were detected in first-trimester placenta, whereas only GnRH I was detected in tissues obtained at term. Both hormones were further immunolocalized to the mononucleate villous and distinct subpopulations of extravillous cytotrophoblasts of the placenta in vivo and in vitro. In contrast, GnRH I but not GnRH II was expressed in the outer multinucleated syncytial trophoblast layer of first trimester chorionic villi and in cultures of villous cytotrophoblasts allowed to undergo differentiation and fusion in vitro. GnRH I and GnRH II were also found to be coexpressed in first-trimester decidua and primary cultures of decidual stromal cells. Collectively, these observations demonstrate that GnRH I and GnRH II have both common and discrete cellular distributions in the placenta and decidua and suggest that these two hormones are capable of eliciting their biological actions in an autocrine and/or paracrine manner within and between these maternal and fetal cellular compartments.

C.D.M. and P.C.K.L. contributed equally to these studies.

This work was supported by an operating grant from the Canadian Institutes of Health Research (to P.C.K.L. and C.D.M.). P.C.K.L. is the recipient of a Senior Investigatorship from the Michael Smith Foundation for Health Research. C.D.M. is a Career Investigator of the British Columbia Research Institute for Children’s and Women’s Health.

Abbreviations: E-cad, E-cadherin; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GnRHR, GnRH I receptor; MMP, matrix metalloproteinase; uPA, urokinase plasminogen activator.

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