Hypoxia Inhibits Activin A Production by Term Villous Trophoblast In Vitro

Abstract

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 vitro hypoxia on the production of inhibin A, activin A and its binding protein follistatin in term villous placental explants (n=4–7) and trophoblast monolayer cultures (n=4). Explants and trophoblasts were incubated for 24–72h under either normoxic (21 per cent O2) or hypoxic (2 per cent O2) conditions. Production of activin A, inhibin A, and follistatin was determined by specific ELISA. After 48h of hypoxia, villous explants exhibited a significant reduction in activin A production rates to 53.2±8.9 per cent (mean±sem , P< 0.05) of normoxic controls which was sustained after 72h in culture (46.8±5.9 per cent), whereas production by trophoblast monolayers was not affected by hypoxia. Follistatin production was decreased to 53.7±9.2 per cent of control (P< 0.05) after 48h of hypoxia. 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 vitro. 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.