detirelix and histrelin

Early human trophoblast shows dramatic invasive properties during early pregnancy. The simultaneous synthesis of matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) in both human trophoblast and decidual membranes suggests that their controlled and balanced expression is crucial for the rapid matrix remodeling and controlled invasion during early pregnancy. Recently, we have described the presence of an extrahypothalamic GnRH immunologically, biologically and chemically identical to the hypothalamic hormone in periimplantation human embryos. Moreover, the production of this decapeptide by the human trophoblast during the early stages of placentation is well documented. TIMP-1 and -3 messenger ribonucleic acid (mRNA) expression in cultured stromal cells and protein secretion into the medium were significantly decreased by GnRH agonist compared to that in control groups. Moreover, expression of TIMP-1 was affected to a greater extent than that of TIMP-3. GnRH antagonist ablated the down-regulation of TIMPs by the GnRH agonist. MMP-9 mRNA expression was not detected in the control groups or in the groups treated with GnRH analogs. Our results provide evidence that trophoblastic GnRH may play an important role in placental tissue organization and in the early embryo-maternal dialogue by enhancing trophoblast invasion through the specific inhibition of TIMPs.

Topics: Adult; Blotting, Western; Collagenases; Culture Media, Conditioned; Embryo Implantation; Endometrium; Female; Gene Expression Regulation; Gonadotropin-Releasing Hormone; Humans; Matrix Metalloproteinase 9; Polymerase Chain Reaction; Pregnancy; Prolactin; RNA, Messenger; Stromal Cells; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-3

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 microM) 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.

Topics: Animals; Blastocyst; Embryonic and Fetal Development; Gene Expression Regulation, Developmental; Gonadotropin-Releasing Hormone; Mice; Mice, Inbred Strains; Morula; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Zygote