Role of activin A as a mediator of in vitro endometrial stromal cell decidualization via the cyclic adenosine monophosphate pathway

Abstract

Objective To elucidate the regulation and role of activin A in endometrial stromal decidualization. Design In vitro model of human stromal cell decidualization with cyclic adenosine monophosphate (cAMP) used to evaluate expression of activin A and to evaluate the effect of the addition of follistatin, a known activin inhibitor, on expression of the decidualized phenotype (as measured by levels of insulin-like growth factor binding protein-1 [IGFBP-1]). Setting Academic research environment. Patient(s) Four premenopausal, normally cycling subjects (age range: 32–40 years). Intervention(s) Endometrial samples were obtained from the subjects after informed consent was obtained. Endometrial stromal cells were treated with cAMP (decidualizing stimulus) and 50 ng/mL, 100 ng/mL, and 200 ng/mL of follistatin for 48 hours. Main outcome measure(s) Levels of IGFBP-1 secreted from cells decidualized in the absence and presence of three different concentrations of follistatin. Result(s) Addition of follistatin, a known binding protein inhibitor of activin A, resulted in a dose-dependent inhibition of IGFBP-1 secreted into conditioned medium, with the greatest decrease observed at 4 days of decidualization. Cells treated with cAMP and 50 ng/mL, 100 ng/mL, and 200 ng/mL of follistatin demonstrated 67.3%, 58.6%, and 35.5%, respectively, of the IGFBP-1 levels observed with cAMP but without follistatin. Conclusion(s) These data suggest that activin A is a necessary component of the cAMP pathway leading to endometrial stromal decidualization. The role of activin A in regulating endometrial stromal decidualization and its known promotion of the invasive phenotype of the trophoblast suggest unique autocrine and paracrine interactions at the maternal/fetal interface during implantation, which might have important clinical implications for the understanding and treatment of fertility and pregnancy disorders.