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University of Alberta, Edmonton Alberta, Canada T6G 2S2
Address all correspondence and requests for reprints to: Dr. D. W. Morrish, 362 Clinical Wing, Heritage Medical Research Centre, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Abstract
Previously, no inhibitors of placental differentiation have been described. In this study, we determined the effect of transforming growth factor β1 (TGFβ1) on cytotrophoblast differentiation. Monolayer cultures of pure cytotrophoblasts were exposed to 0.001–10 ng/ml TGFβ1 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 TGFβ1. Basal human (h)CG and h-placental lactogen (PL) release were reduced compared to control by fractions of 0.75 (TGF β1/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 TGFβ1. Dose-response studies showed that maximal TGFβ1 inhibition of EGF-stimulated hormone secretion occurred at 0.1 ng/ml or more TGFβ1. Partial differentiation (syncytium formation) occurred despite the presence of TGFβ1, suggesting a portion of cytotrophoblasts were committed to differentiation at the time of culture. We conclude that TGFβ1 acts as a major inhibitor of trophoblast differentiation and concomitant peptide hormone secretion.
Received December 7, 1990.
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