Elevated expression and reduced phosphorylation of uterine RIG-I protein in pathogenic preterm labor in mice

Unlike TLRs, the regulation of RIG-I-like receptors (RLRs) in preterm labor (PTL) is not well understood. It is unclear if the RLR pathway is activated in uterine tissue during preterm labor and whether this activation is specific to pathogenic agents. This study aimed to elucidate the regulation of the RLR pathway in two preterm labor models. On gestation day 16, preterm labor was induced in mice using LPS for pathogenic inflammation and RU486, a progesterone antagonist, for nonpathogenic inflammation. The rates of preterm labor and fetal viability were assessed, and uterine tissue was collected for ELISA, real-time PCR, immunohistochemistry for RIG-I, and Western blot analysis of RIG-I and downstream proteins. Spontaneous and agonist-induced uterine contractility were also evaluated. Preterm labor was induced 8-10 hours after LPS and 16-18 hours after RU486 administration. Histopathological analysis showed inflammatory changes and neutrophilic infiltration in uterine tissues. Peripheral leukocyte count, TNFα, and IL-6 levels were significantly higher in both LPS- and RU486-treated groups. Agonist-induced uterine contractility was notably reduced in LPS-treated mice. RIG-I mRNA and protein expression were significantly elevated in LPS-treated animals, with decreased RIG-I phosphorylation, while RU486 treatment did not affect these parameters. IRF3 and its phosphorylated form were significantly increased in both preterm labor models. Additionally, interferon-β and lactate levels were elevated in both groups. The findings suggest that the RLR pathway is activated specifically in the pathogenic model of murine preterm labor through increased RIG-I expression and decreased phosphorylation.