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Interleukin 1ß and Progesterone Stimulate Activin A Expression and Secretion From Cultured Human Endometrial Stromal Cells

Marco Rossi, PhD

Department of Pediatrics, Obstetrics & Reproductive Medicine, University of Siena, Italy

Paola Viganò, PhD

Molecular Laboratory Auxologic Centre, Milan, Italy

Stefano Luisi, MD,PhD

Michela Torricelli, MD

Paulo B. Torres, MD

Department of Pediatrics, Obstetrics & Reproductive Medicine, University of Siena, Italy

Anna Maria Di Blasio, MD,PhD

Molecular Laboratory Auxologic Centre, Milan, Italy

Felice Petraglia, MD

Chair of Obstetrics & Gynecology, Department of Pediatrics Obstetrics & Reproductive Medicine, University of Siena, Policlinico "Le Scotte,"Viale Bracci, 53100 Siena, Italy; petraglia{at}unisi.it

Steroid hormones, cytokines, and growth factors have a major role in evoking local endometrial changes needed for trophoblast implantation. In the present study, the effect of interleukin-1ß (IL-1ß), 17-ß estradiol (E2), and progesterone (Pr) on activin A and follistatin (FS) secretion from cultured human endometrial stromal cells (HESCs) is evaluated. HESCs were obtained from healthy human endometrial samples (n = 8) collected from healthy women. The cells were cultured and stimulated with E2 (10^-7 M, 10^-6M), Pr (10^-7M, 10^-6M), IL-1ß (500 pg/mL), IL-1ß (500 pg/mL) + E2 (10^-6M), and IL-1ß (500 pg/mL) + Pr (10^-6M). Activin A and FS secretion and mRNA expression were assayed by enzyme-linked immunosorbent assay and semiquantitative reverse transcriptase-polymerase chain reaction, respectively. Pr (10^-7 M, 10^-6 M) significantly increased activin A secretion and mRNA expression from HESCs, but E2 did not show remarkable effects. The addition of IL-1ß (P< .001), IL- 1ß + E2 (P < .01), and IL-1ß + Pr (P< .001). significantly stimulated activin A secretion and mRNA expression, compared to untreated cells. Activin A expression and secretion after the coincubation of IL-1ß+ Pr were significantly higher than after IL-1ßand IL-1ß+ E2 stimuli ( P< .01 and P< .001, respectively). Neither Pr nor E2 and IL-1ß had a significant effect on FS secretion and expression. IL-1ßand Pr stimulated activin A but not FS secretion from cultured HESCs, and the effect of IL-1ßwas augmented by Pr. These findings, together with the evidence that activin A is involved in trophoblast implantation, suggest the existence of a complex cross-talk by which the ovary, through Pr secretion, and the embryo, through IL-1ß production, may trigger the endometrial induction of activin A and consequently timing implantation.

Key Words: Activin A • follistatin • cytokines • embryo • pregnancy • implantation

Reproductive Sciences, Vol. 14, No. 1, 29-36 (2007)
DOI: 10.1177/1933719106298191


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