NLRP3 inflammasome inhibition by MCC950 reduces embryo implantation during early pregnancy in mice.

Abstract

Background: Successful pregnancy relies on the healthy completion of implantation, decidualization, and placentation. Additionally, the balance of the inflammatory response is crucial in processes such as trophoblast invasion, tissue, and vascular remodeling.

Objective: Our study aimed to assess the involvement of the NLRP3 inflammasome pathway during the peri-implantation period in mice treated with and without the NLRP3 inhibitor MCC950.

Materials and methods: Uteri during the estrous phase and uteri and implantation sites on days 1, 4, 5, 6, and 8 of pregnancy from mice with/without MCC950 treatment were collected. Serum was obtained from blood samples. The localization and expression of NLRP3 inflammasome pathway members NLRP3 and Gasdermin D were determined using immunohistochemistry. Additionally, protein levels of NLRP3, Caspase-1, Gasdermin D, IL-1β, and IL-18 were assessed using Western blot, while serum levels of IL-1β and IL-18 were measured using ELISA.

Results: The number of implantation sites in the MCC950-treated mice was lower than in untreated mice. The members of NLRP3 inflammasome pathway were observed to be intensely expressed at the implantation sites. NLRP3 was observed predominantly cytoplasmic on days 5, 6, and 8, while in the MCC950-treated mice, NLRP3 was translocated to the nucleus. Gasdermin D expression in subepithelial stroma cells during embryo implantation and invasion was decreased in the MCC950-treated mice. Serum IL-1β and IL-18 levels were high when embryo implantation began in peri-implantation period.

Conclusions: Our findings suggest that NLRP3 inflammasome pathway and inflammasome-dependent programmed cell death pyroptosis may play role during embryo implantation and decidualization.