Bile acids ameliorates lipopolysaccharide-induced endometritis in mice by inhibiting NLRP3 inflammasome activation

Abstract

Aims: Endometritis is a common inflammatory disorder affecting the reproductive health in both humans and livestock. The NLR family pyrin domain containing 3 (NLRP3) inflammasome has recently been identified as a possible therapeutic target for several inflammatory disorders. Bile acids (BAs) have been shown to possess anti-inflammatory properties by inhibiting the activation of the NLRP3 inflammasome. However, whether BAs ameliorate endometritis by targeting NLRP3 inflammasome remain poorly understood.

Main methods: Female NLRP3^+/+ and NLRP3^-/- mice were subjected to uterine perfusion with lipopolysaccharide (LPS) to establish the endometritis model. For BAs pre-treatment, wild-type mice were administered oral gavage of BAs for seven days followed by uterine perfusion with LPS. All mice were euthanized and the uterine tissues were collected for analysis.

Key findings: The abundances of NLRP3 and interleukin-1 beta (IL-1β) were significantly upregulated in the uterine tissues of endometritis mice. NLRP3 deficiency led to a reduction in the inflammatory response, neutrophil infiltration, and myeloperoxidase (MPO) activity in the uterus, as well as an inhibition of IL-1β secretion. Moreover, BAs pre-treatment successfully decreased LPS-induced upregulation of NLRP3, ASC, and Caspase1, lessened histopathological alteration in the uterus, and notably reduced MPO activity and secretion of IL-1β.

Significance: NLRP3 inflammasome is a promising target for endometritis treatment and BAs exhibit anti-inflammatory properties by repressing NLRP3 inflammasome activation, making them a possible novel therapeutic strategy for endometritis.

Keywords: Bile acids; Endometritis; Inflammation; NLRP3.