Term and Preterm Birth Initiation Is Associated with the Macrophages Shifting to M1 Polarization in Gestational Tissues in Mice

SIMPLE SUMMARY: Inflammatory responses are critical in term and preterm labor initiation. The present study represents the inflammatory states in the mouse models’ key tissues associated with labor processes, such as placenta and uterine tissues decidua and myometrium, at the time of labor at term and preterm. We found that the infiltration of neutrophils and macrophages were increased in the above tissues at term labor and preterm labor. The expression of the factors such as cytokines and chemokines that are involved in inflammatory responses were also increased in these tissues. Moreover, macrophages exhibited proinflammatory states in these tissues at term and preterm labor. Our data suggest that macrophages shift to proinflammatory phenotypes at term and preterm labor, thereby contributing to the inflammation linked to term and preterm labor initiation. ABSTRACT: Inflammation in gestational tissues plays critical role in parturition initiation. We sought to investigate the leukocyte infiltration and cytokine profile in uterine tissues to understand the inflammation during term and preterm labor in the mouse model. Preterm birth was induced by the administration of lipopolysaccharide (LPS) or RU38486. The populations of leukocytes were determined by flow cytometry. Macrophages were the largest population in the myometrium and decidua in late gestation. The macrophage population was significantly changed in the myometrium and decidua from late pregnancy to term labor and significantly changed at LPS- and RU386-induced preterm labor. Neutrophils, T cells, and NKT cells were increased in LPS- and RU38486-induced preterm labor. The above changes were accompanied by the increased expression of cytokines and chemokines. In late gestation, M2 macrophages were the predominant phenotype in gestational tissues. M1 macrophages significantly increased in these tissues at term and preterm labor. IL-6 and NLRP3 expression was significantly increased in macrophages at labor, supporting that macrophages exhibit proinflammatory phenotypes. NLRP3 inflammasome inhibitor MCC950 mainly suppressed macrophage infiltration in the myometrium at term labor and preterm labor. Our data suggest that the M1 polarization of macrophages contributes to inflammation linked to term and preterm labor initiation in gestational tissues.