Transforming growth factor (TGF)-β1-induced human endometrial stromal cell decidualization through extracellular signal-regulated kinase and Smad activation in vitro: peroxisome proliferator-activated receptor gamma acts as a negative regulator of TGF-β1

Objective To investigate the effect of transforming growth factor (TGF)-β1 on the extracellular signal-regulated kinase (ERK) and Smad pathway and the role of peroxisome proliferator-activated receptor (PPAR)-γ in cultured human endometrial stromal cells. Design Experimental study. Setting Infertility center of a tertiary university hospital. Material(s) Human endometrial tissues obtained by hysterectomy from patients with conditions other than endometrial diseases. Intervention(s) Endometrial stromal cells were cultured under normal laboratory conditions. TGF-β1, rosiglitazone (PPARγ agonist), and PD98059 (ERK inhibitor) were added to endometrial stromal cell culture according to experimental purposes. Main Outcome Measure(s) Cell count, PRL expression, Smad and ERK phosphorylation, cyclooxygenase (COX)-2 expression, and prostaglandin E 2 (PGE 2 ) release. Result(s) TGF-β1 inhibited cellular proliferation and induced the expressions of COX-2, PGE 2 , and PRL of cultured human endometrial stromal cells. These effects may be mediated by Smad and ERK phosphorylation. Treatment with rosiglitazone, a PPARγ agonist, reversed the TGF-β1 effect by antagonizing the activation of ERK and Smad that was induced by TGF-β1. Conclusion(s) PPARγ plays a negative role by directly acting on Smad and ERK phosphorylation in human endometrial cell decidualization that is induced by TGF-β1 in vitro.