title: Transforming growth factor beta 1 inhibits placental differentiation and human chorionic gonadotropin and human placental lactogen secretion.
abstract: Previously, no inhibitors of placental differentiation have been described. In this study, we determined the effect of transforming growth factor beta 1 (TGF beta 1) on cytotrophoblast differentiation. Monolayer cultures of pure cytotrophoblasts were exposed to 0.001-10 ng/ml TGF beta 1 with and without the presence of 10 ng/ml epidermal growth factor (EGF), an inducer of placental differentiation. Over 7 days of culture, in 11 separate experiments, phase contrast microscopy demonstrated marked inhibition of EGF-induced syncytial formation by TGF beta 1. Basal human (h)CG and h-placental lactogen (PL) release were reduced compared to control by fractions of 0.75 (TGF beta 1/control) and 0.54, respectively. EGF alone induced fractional (EGF/control) increases in hCG and hPL release of 2.46 and 2.68, respectively. However, this stimulation was significantly inhibited by 10 ng/ml TGF beta 1. Dose-response studies showed that maximal TGF beta 1 inhibition of EGF-stimulated hormone secretion occurred at 0.1 ng/ml or more TGF beta 1. Partial differentiation (syncytium formation) occurred despite the presence of TGF beta 1, suggesting a portion of cytotrophoblasts were committed to differentiation at the time of culture. We conclude that TGF beta 1 acts as a major inhibitor of trophoblast differentiation and concomitant peptide hormone secretion.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: D W
authors.initials: DW
authors.lastname: Morrish
authors.forename: D
authors.initials: D
authors.lastname: Bhardwaj
authors.forename: M T
authors.initials: MT
authors.lastname: Paras
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D010920:Placenta / Q000166:cytology* / Q000378:metabolism; D010928:Placental Lactogen / Q000378:metabolism*; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014327:Trophoblasts / Q000166:cytology
chemical_list: D006063:Chorionic Gonadotropin; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D010928:Placental Lactogen