Role of lipid mediators in the regulation of inflammation in the uterus: focusing on omega-3 fatty acids

Abstract

Preterm birth occurs in 5% of all pregnancies in Japan, giving a life-long adverse impact on the baby. The regulation of inflammation balance in the uteroplacental system is a key to successful pregnancy. Deterioration of inflammatory regulation in the pregnant uterus is a major factor related to preterm birth. Inflammatory eicosanoids such as prostaglandin （PG）F2α and PGE2, are produced by the omega-6 fatty acid metabolic pathway and play an essential role in the progress of parturition controlling cervical ripening and uterine contraction. In contrast, accumulating evidence have suggested that the metabolic pathway of omega-3 fatty acids is closely involved in pregnancy maintenance with its anti-inflammatory functions physiologically against omega-6-derived substances. Past studies have implied that enhanced intake of omega-3 fatty acid in pregnant women reduces the incidence of preterm birth. Supporting those clinical findings, we previously found that fat-1 transgenic mice which have an omega-3 fatty acid-dominant internal environment were resistant to inflammation induced preterm birth. In the background mechanism, we confirmed that omega-3 fatty acid metabolites such as resolvin and 18-HEPE suppressed uterine inflammation. In this review article, the importance of omega-3 fatty acids in the control of uterine inflammation is discussed from a wide range of perspectives from basic researches to clinical intervention in pregnant women.