Abstract

In this study, we investigate the effects of microRNA-138-5p and GPR124-regulated inflammasome and downstream LIF-STAT and adhesion molecules signaling in human decidual stromal cells. After informed consent was obtained from women aged 25-38 years undergoing surgical termination of the normal pregnancy and spontaneous miscarriage after 6-9 weeks of gestation, human decidual stromal cells were separated from the decidual tissue. Extracellular vesicles with microRNA (miRNA) between cells have been regarded as critical factors for embryo-maternal interactions on embryo implantation and programming of human pregnancy. MicroRNA-138-5p acts as the transcriptional regulator of GPR124 and the mediator of downstream inflammasome. LIF-regulated STAT activation and expression of integrins might influence embryo implantation. Hence, a better understanding of LIF-STAT and adhesion molecules signaling would elucidate the mechanism of microRNA-138-5p- and GPR124-regulated inflammasome activation on embryo implantation and pregnancy. Our results show the purified extracellular vesicles from decidual stromal cells, the microRNA-138-5p-inhibited GPR124 and inflammasome expression, and microRNA-138-5p activated the expression of LIF-STAT and adhesion molecules in human decidual stromal cells. Additionally, the knockdown of GPR124 and NLRP3 through siRNA increases the expression of LIF-STAT and adhesion molecules. Our findings reveal a better understanding the role of extracellular vesicles, microRNA-138-5p, GPR124, inflammasome, and LIF-STAT and adhesion molecules in embryo implantation and programming of human pregnancy.

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