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

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.

Gravidity influences distinct transcriptional profiles of maternal and fetal placental macrophages at term

“…The prevalence of M1 genes and pro-inflammatory markers in MIMs and HBCs could be due to parturition, which is a pro-inflammatory state. Studies suggest that maternal macrophages exhibiting an M1 phenotype promote cervical ripening, uterine contractions, and delivery ( 57 , 89 , 90 ). It is also possible that the switch to an M1-subtype helps protect the fetus and mother from infection following amniotic sac rupture and prevents placental retention.…”

Distinct transcriptional profiles of maternal and fetal placental macrophages at term are associated with gravidity

“…The prevalence of M1 genes and pro-inflammatory markers in MIMs and HBCs could be due to parturition, which is a pro-inflammatory state. Studies suggest that maternal macrophages exhibiting an M1 phenotype promote cervical ripening, uterine contractions, and delivery ( 57, 88, 89 ). It is also possible that the switch to an M1-subtype helps protect the fetus and mother from infection following amniotic sac rupture and prevents placental retention.…”

Melatonin as a Therapy for Preterm Brain Injury: What Is the Evidence?

“…Maintenance of pregnancy requires ongoing meticulously balanced fetomaternal immune adaptations from implantation until labor [ 11 , 19 , 20 ]. PTB, as demonstrated in preclinical animal models, represents a disruption in this immunological balance, causing an increase in the release of proinflammatory cytokines such as tumor necrosis factor (TNF)α, interleukin (IL)-1, IL-6, and IL-8 by maternal macrophages, which are major contributors to the induction of preterm labor, mainly following activation of the NF-κB pathway [ 21 , 22 , 23 ]. Proinflammatory mediators cross the placenta and enter the bloodstream, where they activate the fetal immune system [ 11 , 24 , 25 ].…”