Effect of hypoxia on placental activin A, inhibin A and follistatin synthesis.

Placental activin A and inhibin A output is increased in pre-eclampsia, a condition characterized by placental hypoxaemia, whereas follistatin secretion is unaltered. We investigated whether hypoxia was the basis for elevated placental activin A and inhibin A output. First trimester and term placental explants were grown in 5-6% dissolved O(2) (n=10/trimester) and 200 microM cobalt chloride (CoCl(2),n =6/trimester) to simulate environmental and cellular hypoxia respectively, for up to 72 h. Activin A, inhibin A and follistatin production were compared with control cultures grown in standard media at 20% O(2). In first trimester and term placenta, activin A output declined significantly under 5-6% O(2) (P=0.006 and 0.001 after 48 h respectively). Inhibin A declined significantly under 5-6% O(2), mainly in first trimester placenta (P=0.03, 24h). CoCl(2) significantly elevated activin A production in term placenta (P=0.003, 48 h), whereas inhibin A output was unaffected. Neither low O(2) or CoCl(2) altered follistatin output from first trimester or term placenta. These findings suggest that there may be novel O(2) sensing mechanism/s that down regulate activin A and inhibin A in the placenta and that low O(2) is not the mechanism behind increased placental inhibin A or activin A output in pre-eclampsia.