The secretion and effect of inhibin A, activin A and follistatin on first-trimester trophoblasts in vitro

Objective: The objectives of this study were to investigate the effect of activin A and follistatin on first-trimester cytotrophoblast invasion in culture and to study the secretion of inhibin A, activin A and Follistatin by these cells in vitro. Design and methods: Cytotrophoblasts were isolated from human placental chorionic villous tissue obtained from 6-8, 8-10 and 10-12 weeks gestation. Cells were cultured for 3 days on cell-culture inserts coated with gelatine For invasion studies and in 24-well Culture plates for secretion studies. The effects of activin A (10 ng/ml), Follistatin (100 ng/ml), interleukin 1 beta (IL-1 beta; 1.0 ng/ml) and epidermal growth factor (EGF; 10 ng/ml) on cytotrophoblast invasion were investigated using a nonradioactive invasion assay. Secretion of inhibin A. activin A and follistatin in the presence of EGF, IL-1 beta, activin A and follistatin were measured using in-house ELISAs. Results and conclusion: Activin A, follistatin and EGF had a significant stimulatory effect on cytotrophoblast invasion from 6-10 weeks gestation. IL-1 beta had a significant stimulatory effect at 8-10 weeks and a significant inhibitory effect on invasion at 10-12 weeks gestation. Follistatin also had a significant inhibitory effect on invasion at 10-12 weeks gestation. In the secretion study. activin A secretion at 8-10 weeks was significantly stimulated by IL-1 beta and EGF. At 10-12 weeks, follistatin and EGF had a significant inhibitory effect on activin A secretion. Follistatin secretion was significantly increased in the presence of IL-1 beta at 6-8 weeks gestation. Inhibin A secretion was not significantly altered by EGF, IL-1 beta, activin A and follistatin. These results show that activin A promotes invasion of first-trimester cytotrophoblasts until 10 weeks gestation. There is it difference in the control of secretion of these proteins dependent on the gestation, suggesting that there is a tight regulation in the function of first-trimester trophoblasts depending on the gestational age. European Journal of Endocrinology.