Regulation of Activin A,Inhibin A,and Follistatin Production in Human Amnion and Choriodecidual Explants by Inflammatory Mediators

Abstract

Objective: To determine the effects of inflammatory mediators on the production of activin A, inhibin A, and the binding protein follistatin in term amnion and chroidecidual tissues.

Methods: The effects of interleukin-1β (IL-1β; 1 ng/mL), tumor necrosis factor-α (TNF-α; 10 ng/mL), and bacterial lipopolysaccharide (LSP; 5 μg/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 activin A, inhibin A, and follistatin under basal conditions; choriodecidual production rates were more than tenfold higher than amnion rates. In amnion explants, activin A production was stimulated by IL-1β and TNF-α 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 inhibition and follistatin was 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 activin 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.