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.


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 1beta (IL-1beta; 10 ng/ml) and epidermal growth factor (EGF; 10 ng/ml) on cytotrophoblast invasion were investigated using a non-radioactive invasion assay. Secretion of inhibin A, activin A and follistatin in the presence of EGF, IL-1beta, activin A and follistatin were measured using in-house ELISAs.


CONCLUSIONS
Activin A, follistatin and EGF had a significant stimulatory effect on cytotrophoblast invasion from 6-10 weeks gestation. IL-1beta 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-1beta 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-1beta at 6-8 weeks gestation. Inhibin A secretion was not significantly altered by EGF, IL-1beta, 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.
Bearfield
C
C
Department of Obstetrics and Gynaecology, RFUC Medical School, 86-96 Chenies Mews, London WC1E 6HX, UK.
Jauniaux
E
E
Groome
N
N
Sargent
I L
IL
Muttukrishna
S
S
D028341:Activins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology; D005260:Female; D038681:Follistatin / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000378:metabolism / Q000502:physiology*; D007265:Inhibins / Q000378:metabolism / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology; D010929:Placentation / Q000502:physiology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology*
D006063:Chorionic Gonadotropin; D038681:Follistatin; D007375:Interleukin-1; C422405:activin A; C422362:inhibin A; D028341:Activins; D007265:Inhibins; D004815:Epidermal Growth Factor; D028322:Inhibin-beta Subunits