Increased uterine NLRP3 inflammasome and leucocyte infiltration in a rat model of preeclampsia.

Abstract

The disruption of the inflammatory microenvironment in the uterus affects pregnancy outcome. However, the exact quantification and distribution of leukocyte subpopulations in the uterus in preeclampsia (PE) have not been clearly characterized. Inflammasomes promote the release of proinflammatory cytokines interleukin (IL)-β and IL-18. A higher expression of NLRP3 inflammasome in placentas contributes to excessive inflammation in PE. However, related studies on the uterus are scarce. We aimed to investigate changes in the infiltration of leukocyte subpopulations in decidual and uterine tissues, and explore the role of activation of uterine NLRP3 inflammasomes in PE. Decidual tissues were collected from normotensive pregnant women and preeclamptic women. A PE-like model was established via administration of lipopolysaccharide to normal pregnant rats. Uterine and decidual tissues were collected from all experimental groups. It was found that the number of leukocytes was significantly elevated in decidual and uterine tissues in PE patients compared to normal controls. The leukocytes (predominantly macrophages and NK cells) particularly infiltrated into the decidua and uterine decidua in PE-like rats, and these were sparse in the myometrium. The NLRP3 immunoreactivity in the uterus was extremely little in control rats, its immunoreactivity and caspase-1 immunoreactivity were significantly elevated in the PE-like rats; the mRNA expression results also indicated an upward trend in the activation of NLRP3 inflammasomes. These results support that leucocyte infiltration in the decidua and uterine deciduas, and the activation of NLRP3 inflammasome in the uterus, which participate in the pathogenesis, are responsible for the excessive inflammation at the maternal-fetal interface during PE. This article is protected by copyright. All rights reserved.