OBJECTIVE: This study was performed to clarify the role of HomeoboxA (HOXA) and its related signaling molecules in the decidualization of primary cultured endometrial cells. METHODS: Human endometrial tissues were obtained by curettage of hysterectomy specimens from patients with conditions other than endometrial diseases. Tissues were minced and digested with Trypsin-EDTA for 20 min, 37degrees C. Cells were cultured with DMEM/F12 medium in 37degrees C, 5% CO2 incubator for 24 hrs. Cells were treated with HOXA10 siRNA and added transforming growth factor (TGF)-beta1 (10 ng/mL) for 48 hrs to induces decidualization in vitro. Reverse transcription polymerase chain reaction analysis was accomplished to observe the expression of HOXA10, prolactin, cyclooxygenase (COX)-2, peroxisome proliferator-activated receptor (PPAR)-gamma, and wingless-type MMTV integration site family (Wnt). RESULTS: HOXA10 expression was increased (1.8 fold vs. non-treated control) in TGF-beta1 treated cells. Decidualization marker, prolactin, was significantly increased in TGF-beta1 treated cells compared with HOXA10 siRNA treated cells. Endometrial cell differentiation marker, COX-2 was down-regulated by HOXA10 siRNA even if cells were treated with TGF-beta1. Wnt4 was down-regulated by treated with HOXA10 siRNA, this expression patters was not changed by TGF-beta1. Expression of PPAR-gamma was down regulated by TGF-beta1 in regardless of HOXA10 siRNA treatment. CONCLUSION: TGF-beta1 which is induced by progesterone in endometrial epithelial cells may induces stromal cell decidualization via HOXA10 and Wnt signaling cascade.