Hypoxia inhibits activin A production by term villous trophoblast in vitro

Elevated activin A and inhibin A levels have been associated with pre-eclampsia, a pregnancy-related disorder associated with placental hypoxaemia. We investigated the effect of in Nitro hypoxia on the production of inhibin A, activin A and its binding protein follistatin in term villous placental explants (n = +-7) and trophoblast monolayer cultures (n = 4). Explants and trophoblasts were incubated for 24-72 h under either normoxic (21 per cent 02) or hypoxic (2 per cent 0,) conditions. Production of activin A, inhibin A, and follistatin was determined by specific ELISA. After 48 h of hypoxia, villous explants exhibited a significant reduction in activin in A production rates to 53.2 +/- 8.9 per cent (mean +/- SEM, P<0.05) of normoxic controls which NN as sustained after 72 h in culture (46.8 +/- 5.9 per cent), whereas production bN trophoblast monolayers was not affected by hypoxia. Follistatin production was decreased to 53.7 +/- 9.2 per cent of control (P<0.05) after 48 h of hN poxia. Inhibin A production remained unaltered in both culture systems. Our data demonstrate for the first time that hypoxia lowers term placental activin A and follistatin production in Nitro. These findings do not support the notion that elevated circulating activin A levels in pre-eclampsia originate from the placenta as a result of placental hypoxia. Other as yet unknown maternal/placental factors may contribute to elevated activin A production in women with severe pre-eclampsia. (c) 2002 Elsevier Science Ltd. All rights reserved.