Lack of Annexin A1 Exacerbates Inflammatory Response in Acute Endometritis Model

Annexin A1 (AnxA1) is a glucocorticoid-inducible protein and an important endogenous modulator of inflammation. However, its effect in the endometrial microenvironment is poorly explained. This study aimed to evaluate the role of endogenous AnxA1 in an endometritis mouse model induced by lipopolysaccharide (LPS). Female C57BL/6 wild-type (WT) and AnxA1(-/-) mice were divided into two groups: SHAM and LPS. To induce endometritis, mice received a vaginal infusion of 50 mu L of LPS (1 mg/mL) dissolved in phosphate-buffered saline. After 24 h, the mice were euthanized, and blood and uteri samples were collected. The endometrium inflammatory scores were significantly increased in the LPS-treated group. AnxA1(-/-) mice from the LPS group demonstrated a significant increase in the number of degranulated mast cell levels compared to AnxA1(-/-) SHAM mice. The Western blotting analysis revealed that a lack of AnxA1 promoted the upregulation of NLRP3 and pro-IL-1 beta in the acute endometritis animal model compared to WT LPS animals. LPS-induced endometritis increased the number of blood peripheral leukocytes in both WT and AnxA1(-/-) mice compared with SHAM group mice (p < 0.001). AnxA1(-/-) mice also showed increased plasma levels of IL-1 beta (p < 0.01), IL-6, IL-10, IL-17, and TNF-alpha (p < 0.05) following LPS-induced endometritis. In conclusion, a lack of endogenous AnxA1 exacerbated the inflammatory response in an endometritis model via NLRP3 dysregulation, increased uterine mast cell activation, and plasma pro-inflammatory cytokine release.