The investigation of inflammation-associated programmed cell death pyroptosis in the mouse uterus during peri-implantation period

Objective: A successful pregnancy requires healthy implantation, decidualization and placentation. In addition, the balance of the inflammatory response is important for trophoblast invasion, tissue and vascular remodeling. The NLRP3 inflammasome pathway is involved in the inflammation related programmed cell death pyroptosis. In our study, we aimed to examine the localization and expression of NLRP3, Caspase-1, Gasdermin D, IL-1β and IL-18 in the uterus and implantation sites to determine the role of pyroptosis in the peri-implantive period in mice. Method: Uteri of estrous phase and uteri/implantation sites of 1st, 4th, 5th, 6th and 8th days of pregnancy from mice were obtained. The localization and expression of NLRP3, Caspase-1, Gasdermin D, IL-1β and IL-18 proteins, members of the NLRP3 inflammasome pathway involved in pyroptosis, were determined by immunohistochemistry and Western blot. Results: In mice, NLRP3, Caspase-1, Gasdermin D and IL-18 expressions were observed in the subepithelial stroma cells below the luminal epithelium where the blastocyst was attached on the 5th day of pregnancy. It was observed that NLRP3 was intensively expressed during the proliferation of uterine lumen and gland epithelium in the early stages of pregnancy. In addition, NLRP3 inflammasome pathway members were observed to be expressed during the proliferation and differentiation, decidualisation, of stromal cells that will form the secondary decidual zone. It was observed that IL-1β and IL-18 were expressed more intensely in the secondary decidual zone compared to the primary decidual zone. It was observed that NLRP3 expression decreased in the secondary decidual zone with the progression of pregnancy and the onset of placentation. Conclusion: In our study, our results suggest that inflammation-associated progressive cell death pyroptosis and the NLRP3 inflammasome pathway may play a role in embryo implantation and decidualization. Key words: implantation, decidualization, pyroptosis, inflammasome, NLRP3