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 24-72 h under either normoxic (21 per cent O(2)) or hypoxic (2 per cent O(2)) 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 A production rates to 53.2 +/- 8.9 per cent (mean +/- SEM, P<0.05) of normoxic controls which was sustained after 72 h 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 48 h 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.

• Authors: M Blumenstein, M D Mitchell, N P Groome, J A Keelan
• Journal: Placenta (Placenta) Vol. 23 Issue 10 Pg. 735-41 (Nov 2002) ISSN: 0143-4004 [Print] Netherlands
• PMID: 12398813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Elsevier Science Ltd.

Chemical References

• Follistatin
• activin A
• inhibin A
• Activins
• Inhibins
• Inhibin-beta Subunits
• Oxygen

Topics

• Activins (biosynthesis)
• Cell Hypoxia
• Cells, Cultured
• Enzyme-Linked Immunosorbent Assay
• Female
• Follistatin (biosynthesis)
• Humans
• Inhibin-beta Subunits (biosynthesis)
• Inhibins (biosynthesis)
• Oxygen (administration & dosage)
• Pre-Eclampsia (metabolism)
• Pregnancy
• Trophoblasts (metabolism)