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

Abstract

Objective: The objectives of this study were to investigate the effect of activin A and follistatin on firsttrimester 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 1b (IL-1b; 10 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-1b, 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-1b 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-1b 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-1b at 6-8 weeks gestation. Inhibin A secretion was not significantly altered by EGF, IL-1b, activin A and follistatin. These results show that activin A promotes invasion of first-trimester cytotrophoblasts until 10 weeks gestation. There is a 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 152 909-916

Activin/Nodal Signaling Switches the Terminal Fate of Human Embryonic Stem Cell-derived Trophoblasts

“…Therefore, hESC-derived trophoblasts are capable of forming iCTBs or STBs when exposed to relevant extracellular cues, similar to human placental trophoblasts. Other functional properties of first and third trimester trophoblasts and mouse trophoblasts have been reported, such as their differential response to nodal and activin treatment (58,(73)(74)(75)(76). These should also be tested in hESC-derived trophoblasts, although these studies are beyond the scope of this work.…”

Predicting first trimester pregnancy outcome: derivation of a multiple marker test

“…(21) There have been conflicting results in prior studies applying Activin A as a marker of ectopic pregnancy. A study of patients with PUL found that an Activin A level ≤0.37 ng/mL had 100% sensitivity and 99.6% specificity for the diagnosis of EP.…”

Activin A and Follistatin as Biomarkers for Ectopic Pregnancy and Missed Abortion

“…Within the same period, the magnitude of the stimulatory effect of activin A is greater [24], further indicating that a valuable sampling for related biomarker measurement would be within this interval. In the same study, placental chorionic villous explants were cultured in vitro, and activin A stimulated the outgrowth of cytotrophoblasts into the surrounding matrix, but FS reversed that effect.…”