The role of chorionic gonadotropin (CG) in blastocyst implantation.
Implantation is a complex spatio-temporal interaction between the genotypically different embryo and the mother. Success of this event requires the synchronization of development and effective biochemical communications from both sides. Chorionic gonadotropin (CG), which is a major embryonic signal in the primate, is a glycoprotein hormone synthesized and secreted by the trophoblast. Various isoforms exist in plasma, urine, and blastocyst culture medium, a result of posttranslational modifications. The exponential secretion of CG and its long circulatory half-life extends the life span of corpus luteum to maintain the supply of progesterone during the first 6-8 weeks of pregnancy. To study the direct effects of CG in the uterus, we used the baboon (Papio anubis) as a non-human primate model. In vivo stimulation with CG during the window of uterine receptivity results in further morphologic and biochemical modifications of the receptive endometrium. These are characterized by the plaque reaction in the luminal epithelium, an increase in glycodelin expression and secretion by the glandular epithelium, and the differentiation of subepithelial stromal fibroblasts characterized by expression of the alpha smooth muscle actin (alpha SMA). Pretreatment with progesterone receptor antagonist (PRa) completely or partially inhibits these effects. The signal transduction pathway activated by CG in primate endometrial epithelial cells involves the protein kinase A (PKA)-independent phosphorylation of extracellular signal regulated kinase (ERK 1/2). This alternate signal transduction pathway may prevent CG Receptor (R) downregulation at the implantation site and enhance epithelial cell proliferation and differentiation. Thus, our results suggest that CG plays an important role in implantation in addition to its luteotrophic role.
Srisuparp
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Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL 60612-7313, USA.
Strakova
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Fazleabas
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D017398:Alternative Splicing; D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology*; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000502:physiology*; D003338:Corpus Luteum / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D000071816:Glycodelin; D006023:Glycoproteins / Q000502:physiology; D006031:Glycosylation; D006133:Growth Substances / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010215:Papio; D010766:Phosphorylation; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000502:physiology; D011374:Progesterone / Q000378:metabolism; D020033:Protein Isoforms / Q000502:physiology; D011499:Protein Processing, Post-Translational; D011974:Receptors, LH / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013256:Steroids / Q000494:pharmacology; D017154:Stromal Cells / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
C422565:13beta-methyl 19-nor-steroid; D006063:Chorionic Gonadotropin; D000071816:Glycodelin; D006023:Glycoproteins; D006133:Growth Substances; D006727:Hormone Antagonists; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D011974:Receptors, LH; D011980:Receptors, Progesterone; D013256:Steroids; D011374:Progesterone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins