Study of Molecular Mechanism on Effect of TCDD on Development of Ectopic Endometrium in Mouse

Objective To investigate the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) on development of endometriosis in a mouse model from perspective of molecular mechanism.Methods The endometriosis mouse model was established with autotransplantation of endometrium.Twenty-one days prior to induction surgery which produces endometriosis,female mice were pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) at 0,3,or 10 mg TCDD /kg.Animals were treated again at the time of surgery and at 3,6,and 9 weeks following surgery.Evaluation of ectopic focuses diameter were made at 3,6,9 weeks post surgery.The AhR and CYP1A1 expression on ectopic endometrium were identified by immunohistochemistry and RT-PCR assays.Results ①With increased time and dose of TCDD exposure,it produced a dose-dependent increase in endometriotic site diameter when all time points were pooled within each dose in mice(r=0.727 and 0.553 respectively,both P0.05).②The expression of AhR protein on ectopic focuses in mice were higher in the TCDD exposure group than those in control group,and presented time-dose dependent increase(r=0.687 and 0.442,both P0.01).③The higher dose of exposure increased,the higher CYP1A1 protein expressions enhanced(r=0.640,P0.01).④As compared with the control group,the expression of AhR mRNA in ectopic focuses of mice were higher in the TCDD exposure group,and show time-dose dependent increase(r=0.565 and 0.635,both P0.01).⑤The higher dose of exposure increased,the higher CYP1A1 mRNA expression enhanced(r=0.659,P0.01).Conclusion TCDD can promote progression of ectopic focus of endometriosis in the mouse model,and one of molecular mechanism of TCDD for development of EMS is the activated AhR and its reaction gene of CYP1A1.The activated AhR and CYP1A1 can be acted as biochemical indicator to TCDD exposure.