The role of maternal–foetal interface inflammation mediated by NLRP3 inflammasome in the pathogenesis of recurrent spontaneous abortion

Abstract

IntroductionApproximately half of the recurrent spontaneous abortions (RSAs) that remain unidentified to date may be closely related to inflammation. Our previous study found excessive NLRP3 inflammasomes in RSA patients. Here, we investigated further the role of inflammasomes in the maternal–foetal interface of RSA patients. MethodsVillous and decidual tissues were collected during uterine curettage. The trophoblast cell line TEV-1 was cultured with lipopolysaccharide (LPS) or low molecular weight heparin (LMWH), and then the macrophage cell line RAW264.7 was treated with trophoblast media. The expression and localisation of inflammasomes in tissues and cells were detected, and the migration and proliferation of cells were analysed. ResultsA significantly increased expression of inflammasomes was observed in RSA tissues compared with those in the normal group, and it was more obvious in villous tissues than in decidual tissues. In TEV-1 cells, after LPS stimulation, the expression of inflammasomes was increased, but the cell activity was decreased, whereas in RAW264.7, both expression of inflammasomes and cell activity were increased in the LPS group. In addition, LMWH could inhibit the action of LPS in above cells. DiscussionIn patients experiencing RSA, abnormal inflammatory response might be mediated by NLRP3 inflammasomes on the maternal–foetal interface, which may reduce trophoblast activity and promote macrophage activity, leading to early embryo implantation failure. LMWH is expected to treat RSA patients by blocking this process.