Role of activin A as a mediator of in vitro endometrial stromal cell decidualization via the cyclic adenosine monophosphate pathway.
OBJECTIVE
To elucidate the regulation and role of activin A in endometrial stromal decidualization.


METHODS
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]).


METHODS
Academic research environment.


METHODS
Four premenopausal, normally cycling subjects (age range: 32-40 years).


METHODS
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.


METHODS
Levels of IGFBP-1 secreted from cells decidualized in the absence and presence of three different concentrations of follistatin.


RESULTS
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.


CONCLUSIONS
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.
Tierney
Emily P
EP
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5317, USA.
Giudice
Linda C
LC
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000008:administration & dosage; D028341:Activins / Q000378:metabolism / Q000502:physiology*; D000328:Adult; D000242:Cyclic AMP / Q000502:physiology*; D003656:Decidua / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D038681:Follistatin / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D028322:Inhibin-beta Subunits / Q000378:metabolism / Q000502:physiology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D038681:Follistatin; D018970:Insulin-Like Growth Factor Binding Protein 1; C422405:activin A; D028341:Activins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D028322:Inhibin-beta Subunits; D000242:Cyclic AMP