Study On Akkermansia Muciniphila's Inflences On Endometrial Hyperplasia Model Mice And Possible Mechanism

Objective Illustrate the effect and possible mechanism of Akkermansia muciniphila on endometrial hyperplasia mice,and looking for the specific therapeutic target of endometrial hyperplasia.Methods1.Devided 8-week-C57BL/6J mice into five groups: E2-AKK(n=10),E2-PBS(n=12),EC-FMT(n=10),H-FMT(n=10)and NC(n=10).Group E2-AKK and E2-PBS were implanted Estradiol sustained-release granules subcutaneous after ovariectomy to establish endometrial hyperplasia model,and gavaged with AKK or PBS postoperative.Group EC-FMT and H-FMT were gavaged with fecal suspension from one endometrial adenocarcinoma patient staged G1 or one healthy female.Group NC were raised conventionally without any treatment.2.QPCR was used for determination of Akkermansia muciniphila in mouse feces.3.ELISA was used to determine the concentration of IL-6 and E2 in mouse serum.4.Immunohistochemistry was used to detect the expression of ER,PR,PTEN,?-catenin,PAX2 and aromatase in mouse endometrial.Results1.Implanting Estradiol sustained-release granules subcutaneous to mice after ovariectomy can establish endometrial hyperplasia model,whose success rate reached 100%.2.Mice from group E2-AKK and group E2-PBS gained most weight during this experiment compared with group NC(P<0.0001);Mice from group EC-FMT gained more weight compared with group H-FMT(P<0.05).3.AKK colonized in the intestine after gavaging.Gastrointestinal AKK subtype colonization in group E2-AKK is much higher than group E2-PBS and group NC(P<0.001).4.ELISA results showed that serum concentration of E2 and IL-6 in group E2-AKK and E2-PBS is higher than group NC(P<0.05);serum concentration of IL-6 in group EC-FMT is higher than group H-FMT and group NC(P<0.05).5.Immunohistochemical showed that ER,?-catenin and aromatase increased in group E2-AKK and E2-PBS comparing with group NC,while PR and PTEN decreased(P<0.01).ER,?-catenin and aromatase increased in group E2-PBS,meanwhile PR,and PTEN decreased comparing with group E2-AKK(P<0.01).ER and aromatase increased in group EC-FMT than both group H-FMT and group NC(P<0.05).Conclusions1.Implanting Estradiol sustained-release granules subcutaneous to mice after ovariectomy can establish endometrial hyperplasia model.2.Akkermansia muciniphila may reduce the production of aromatase by reducing the production of IL-6,thereby reducing the synthesis of E2,delaying the progress of endometrial hyperplasia in mice.3.Akkermansia muciniphila and intestinal flora transplantation may be a new target for the treatment of endometrial hyperplasia.