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 mum cobalt chloride (CoCl2, 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, 24 h). CoCl2 significantly elevated activin A production in term placenta (P=0.003, 48 h), whereas inhibin A output was unaffected. Neither low O-2 or CoCl2 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 02 is not the mechanism behind increased placental inhibin A or activin A output in pre-eclampsia. (C) 2002 Elsevier Science Ltd. All rights reserved.