2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the expression of cyclooxygenase-2 and aromatase cytochrome P450 in human endometrium

Abstract

To investigate the role of 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) on eutopic endometrium by stromal cell culture. Prospective experimental study. Human endometrial tissues obtained by hysterectomy specimens from 16 women with estrogen dependent diseases (endometriosis (n = 4), adenomyosis (n = 5), uterine fibroids (n = 7)) and 5 women who had undergone hysterectomy for carcinoma in situ of uterine cervix. Endometrial stromal cells were cultured under the following conditions: DMEM/F12 (10% FBS, 1 nM E2 and 100 nM P4). TCDD (10 nmol/l) and TNF-a (0.1ng/ml) were added according to experimental purposes. The protein expression of aromatase cytochrome P450 and COX-2 was examined by Western blot. In control group, the COX-2 protein in stromal cells cultured with TCDD was significantly increased (control; 0.63 ± 0.19 vs. TCDD; 0.94 ± 0.26, P<0.05) And the aromatase P450 protein in stromal cells cultured with TCDD and TCDD plus TNF-a was significantly increased. (control; 0.60 ± 0.26 vs. TCDD; 0.90 ± 0.36, TCDD plus TNF-a; 0.95 ± 0.43, P<0.05). In study group, the COX-2 protein in stromal cells cultured with TCDD and TCDD plus TNF-a was significantly increased. (control; 0.81 ± 0.26, TCDD; 1.04 ± 0.38, TCDD plus TNF-a; 1.30 ± 0.90, P<0.05). And the aromatase P450 protein in stromal cells cultured with TNF-a and TCDD and TCDD plus TNF-a was significantly increased (control; 0.76 ± 0.18 vs. TNF-a; 0.93 ± 0.34, TCDD; 0.97 ± 0.41, TCDD plus TNF-a; 1.16 ± 0.41 P<0.05). In the stromal cell cultured with TCDD plus TNF-a than TNF-a and TCDD alone, the aromatase protein was significantly increased (P<0.05). Treatment with the TCDD increased aromatase cytochrome P450 and COX-2 on the eutopic endometrium of patients with and without estrogen dependent diseases, by endometrial stromal cells in culture.