Regulation Of Monosodium Urate Crystal On Mouse Decidualization

The success of embryo implantation requires embryonic development to the blastocyst stage,and the endometrium establishes receptivity.The uterus have the decidua reaction after implantation,but the initiation mechanism of this process is currently unclear.Monosodium urate crystal is one of the important molecules for endogenous induction of sterile inflammation.Intracellular purine metabolism produces a high concentration of uric acid,which releases to the outside of the cell once the cell ruptures.Uric acid combines with sodium ions to form monosodium urate crystals,then monosodium urate crystal stimulates the inflammatory response.In this experiment,we examined the localization of uric acid crystals in uteri of normal pregnant mice and artificially induced decidual mice by immunofluorescence and mouse pseudopregnancy models,and checked the expression of inflammatory factors in mouse endometrium stimulated by uric acid crystals by alkaline phosphatase staining,real-time quantitative PCR and Western blot.In addition,we also used in situ hybridization to detect the expression of xanthine oxidase in early pregnancy.Combined with in vitro and in vivo experiments,the aim of our study was to show whether monosodium urate crystals can stimulate the early decidualization.The results of immunofluorescence showed that there was a small amount of monosodium urate crystal signal in the implantation site of pregnant day 5 mice.The monosodium urate crystal fluorescence signal appeared in the mouse uterine luminal epithelial and stromal cells 1 h after the injection of oil into the uterine horn of the pseudopregnant D4 mice.Using artificial decidualization model,monosodium urate crystals were injected into the uterine horn of pseudopregnant day 4 mice,and it could induce the formation of deciduoma,which was consistent with the results of oil-induceddecidualization.Monosodium urate crystal can stimulate the expression of Dtprp in the mouse primary endometrial stromal cells.After stimulation with monosodium urate crystals,the early inflammatory molecules Cox2,Il-11 and Cxcl1 were up-regulated.The up-regulation trend of these inflammatory factors was consistent with the change that occurred after implantation in early pregnancy.In situ hybridization showed that the xanthine oxidase m RNA was expressed in uterine epithelial cells before embryo implantation,and was not expressed in stromal cells.After embryo implantation,xanthine oxidase was expressed in the subepithelial stromal cells and its expression is gradually enhanced.Treatment of ovariectomized mice with steroid hormones revealed that Xdh m RNA expression was regulated by estrogen.Using the xanthine oxidase inhibitor Allopurinol to inhibit the uric acid synthesis in mouse stromal cells,the expression of Dtprp in the stromal cells of m ESC could be significantly decreased.Our results show that monosodium urate crystal can induce mouse decidualization by up-regulating proinflammatory cytokines,suggesting that monosodium urate crystal may play an important role in mouse decidualization.