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

Abstract

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-1 β (IL-1 β), 17-β 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, 10⁻⁶ M), Pr (10⁻⁷ M, 10⁻⁶ M), IL-1 β (500 pg/mL), IL-1 β (500 pg/mL) + E2 (10⁻⁶ M), and IL-1 β (500 pg/mL) + Pr (10⁻⁶ M). 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-1 β (P <.001), IL-1β + E2 (P <.01), and IL-1 β + 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-1 β + Pr were significantly higher than after IL-1 β and IL-1 β + E2 stimuli (P <.01 and P <.001, respectively). Neither Pr nor E2 and IL-1 β had a significant effect on FS secretion and expression. IL-1 β and Pr stimulated activin A but not FS secretion from cultured HESCs, and the effect of IL-1 β was 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-1 β production, may trigger the endometrial induction of activin A and consequently timing implantation.