Regulation of activin A, inhibin A, and follistatin production in human amnion and choriodecidual explants by inflammatory mediators

OBJECTIVE: To determine the effects of inflammatory mediators on the production of acfivin A, inhibin A, and the binding protein follistatin in term amnion and choriodecidual tissues.METHODS: The effects of interleukin-1 beta (IL-1 beta; 1 ng/mL), tumor necrosis factor-alpha (TNF-alpha; 10 ng/mL), and bacterial lipopolysaccharide (LPS; 5 mu g/mL) on production rates of activin A, inhibin A, and follistatin by term choriodecidual and amnion membranes in explant culture were determined using specific enzyme-linked immunoabsorbent assays.RESULTS: All explants (n = 6 placentas) produced detectable amounts of activity A, inhibin A, and follistatin under basal conditions; choriodecidual production rates were move than tenfold higher than amnion rates. In amnion explants, activin A production was stimulated by IL-1 beta and TNF-alpha to 450 +/- 155.4% and 531 +/- 170.8% of control, respectively (mean +/- standard error of the mean; P <.05 by analysis of variance), whereas production of inhibin and follistatin runs stimulated to a much more modest extent. Similar responses were observed in the choriodecidual explants. Lipopolysaccharide had no significant effect on amnion activin A production, but stimulated choriodecidual production to 290 +/- 34% of control. Lipopolysaccharide exerted only limited effects on inhibin A and follistatin production.CONCLUSIONS: Treatment with proinflammatory mediators resulted in a preferential increase in acfivin A production compared with that of inhibin A or follistatin. These findings suggest that inflammation of the gestational membranes could result in increased local activin A production and bioactivity. Copyright (C) 2000 by the Society for Gynecologic Investigation.