Benzo(a)Pyrene Interferes Apoptosis Of Endometrium Cells Via Wnt5a Pathway During Peri-implantation

Objective: It is well known that Benzo(a)pyrene(BaP)is an endocrine-disrupting pollutant present in many aspects of daily life.We previously showed that BaP affects the morphology of the endometrium,disrupts the balance of estrogen and progesterone,lead to decrease number of implantation sits.However,the mechanism is unclear.Endometrial function is crucial to implantation,which is associated with endometrial apoptosis.In this study,we focus on the effect of BaP on apoptosis of endometrium and the role of Wnt Signaling during this process.Method:Pregnant mice were gavaged with corn oil in control group and 0.2mg/kg/day BaP in treatment group from day1 to day6 of pregnancy.1.The expression of Hox A10 was measured by Western blot and Immunohistochemistry.2.Western blot,Immunohistochemistry were used to detect the protein expression and location of Wnt5 a,?-catenin,GSK-3?.3.Western blot was used to detect the expression of BAX,BCL2,Caspase3;TUNEL were used to detect apoptosis of endometrium cells.Human endometrial stromal cell was treated with different concentrations of BaP1.Western blot was employed to examine the expression of Wnt genes,and apoptosis-related genes.2.Apoptosis of human endometrial stromal cell was detected by Flow cytometry.3.Immunofluorescence was used to observe the protein expression and location of ?-catenin.Results1.The expression of HoxA10 was decreased in BaP-treated group,Wnt5 a and ?-catenin were activated by BaP.The result of Western blot and TUNEL showed a less apoptosis of endometrial cell after BaP-treatment.2.The expression of Wnt genes in human endometrial stromal cell was consistent with the changes in vivo.Flow cytometry revealed a decreased apoptosis in BaP-treated group.3.After been treated with recombinant Wnt5 a protein,the expression of Wnt5 a in human endometrial stromal cell was increased,and the expression of apoptosis genes was decreased.These changes were restored after adding sfrp5 in BaP and Wnt5 a treated groups respectively.Conclusion:Wnt5a and ?-catenin were aberrantly increased after BaP exposure,and the apoptosis of endometrium cell was decreased.These datas indicated that the balance of Wnt Signaling was disturbed by BaP,which influence the banance of apoptosis in endometrial cell,and then may destroy the function of endometrium,finally lead to a damage of embryo implantation.