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The Role of Gonadotropin-Releasing Hormone in Murine Preimplantation Embryonic Development¹

Department of Gynecology and Obstetrics, Reproductive Immunology Laboratory, Stanford University School of Medicine (F.R., E.M.C., J.K., Y.W., M.L.P.), Stanford, California; and the Department of Obstetrics and Gynecology, University of Valencia School of Medicine (F.R., E.M.C., F.B.-M.), and the Center for Gynecology and Obstetrics (F.R., E.M.C., F.B.-M.), 46004 Valencia, Spain

Address all correspondence and requests for reprints to: Francisco Raga, M.D., Center for Gynecology and Obstetrics, Navarro Reverter 11–1, 46004 Valencia, Spain. E-mail: cegiob{at}interbook.net

Previous studies have established the presence of an extrahypothalamic GnRH in a variety of tissues. GnRH receptor is known to be present in the placenta, which produces and secretes the decapeptide from the very early stages of placentation. We hypothesized that GnRH may play a role in the preimplantation development of embryos. To examine this hypothesis, we assessed GnRH and GnRH receptor messenger RNA (mRNA; RT-PCR) and protein expression (Immunohistochemistry) in preimplantation murine embryos at various developmental stages. Furthermore, preimplantation murine embryos were cultured with GnRH agonist and antagonist in vitro to assess the influence of GnRH analogs on embryo development.

GnRH is expressed in the developing mouse embryo from morula to hatching blastocyst stages at the mRNA and protein levels. GnRH receptor mRNA is also present in the developing embryos studied.

Preimplantation embryonic development was significantly enhanced by incubation with increasing concentrations of GnRH agonist and is significantly decreased by GnRH antagonist compared with that in the control group. Moreover, GnRH antagonist (5 and 10 µM) was able to completely block embryo development. The deleterious effect of GnRH antagonist on embryo development was reversed by increasing concentrations of the agonist, as determined by the number of embryos reaching the blastocyst stage.

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