title: Human chorionic gonadotropin contributes to maternal immunotolerance and endometrial apoptosis by regulating Fas-Fas ligand system.
abstract: The first known hormonal signal of the conceptus during implantation is human chorionic gonadotropin (hCG). Interestingly, increased apoptosis in human endometrium coincides with the implantation window. Factors from the fetal or placental origin as well as maternal hormonal factors are likely to have a potential role in the regulation of apoptotic signaling molecules. We hypothesized that hCG may be a placental link for the development of local maternal immunotolerance. Fas-Fas ligand (FasL) system is one of the apoptotic signaling pathways, shown to be important in the development of local immune tolerance during and after implantation. We report that hCG treatment decreases cell proliferation and increases apoptosis in endometrial cells. Moreover, hCG stimulates FasL mRNA and protein expression without affecting Fas mRNA in these cells. Interestingly, in coculture experiments, hCG-treated endometrial cells induce an increase in T cell apoptosis. Our in vivo results reveal that cells of early pregnancy decidua express strong FasL immunoreactivity, and decidual areas containing interstitial cytotrophoblasts have numerous TUNEL-positive cells. Compared with decidual areas devoid of interstitial cytotrophoblasts, we observed in decidual areas containing interstitial cytotrophoblasts clearly less amount of TUNEL-positive cells. These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance and may facilitate the trophoblast invasion by regulating proapoptotic molecules such as FasL in endometrial cells.
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Umit A
authors.initials: UA
authors.lastname: Kayisli
authors.forename: Belgin
authors.initials: B
authors.lastname: Selam
authors.forename: Ozlem
authors.initials: O
authors.lastname: Guzeloglu-Kayisli
authors.forename: Ramazan
authors.initials: R
authors.lastname: Demir
authors.forename: Aydin
authors.initials: A
authors.lastname: Arici
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000502:physiology*; D018920:Coculture Techniques; D003656:Decidua / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D004717:Endometrium / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
chemical_list: D006063:Chorionic Gonadotropin; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor