title: 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.affiliation: Liggins Institute, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand. m.blumenstein@auckland.ac.nz
authors.forename: M
authors.initials: M
authors.lastname: Blumenstein
authors.forename: M D
authors.initials: MD
authors.lastname: Mitchell
authors.forename: N P
authors.initials: NP
authors.lastname: Groome
authors.forename: J A
authors.initials: JA
authors.lastname: Keelan
mesh_terms: D028341:Activins / Q000096:biosynthesis*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D038681:Follistatin / Q000096:biosynthesis; D006801:Humans; D028322:Inhibin-beta Subunits / Q000096:biosynthesis*; D007265:Inhibins / Q000096:biosynthesis; D010100:Oxygen / Q000008:administration & dosage; D011225:Pre-Eclampsia / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D038681:Follistatin; C422405:activin A; C422362:inhibin A; D028341:Activins; D007265:Inhibins; D028322:Inhibin-beta Subunits; D010100:Oxygen