Pharmacological Activation Of Rev-Erb Alpha Suppresses Lps-Induced Macrophage M1 Polarization And Prevents Pregnancy Loss

Background: Circadian rhythm is an important player for reproduction. Rev-erb alpha, a significant clock gene, is involved in regulating cell differentiation, inflammation and metabolism. Macrophage polarization plays crucial roles in immune tolerance at the maternal-fetus interface, which also modulates the initiation and resolution of inflammation. Alteration of macrophage polarization induces adverse pregnancy outcomes such as infertility, recurrent spontaneous abortion and preterm labor.Results: Decidual macrophages from LPS-induced mice abortion model displayed M1-like bias, accompanied by decreased expression of Rev-erb alpha. SR9009, an agonist of Rev-erb alpha, may reduce lipopolysaccharide (LPS)-induced M1 polarization of macrophages via activation of PI3K but not NF-kappa B signaling pathway. Furthermore, SR9009 could reduce M1-like polarization of decidual macrophages induced by LPS and attenuate LPS-induced resorption rates in mice model.Conclusions: Both in vivo and in vitro experiments demonstrated that the pharmacological activation of Rev-erb alpha using SR9009 could attenuate the effect of LPS on macrophage polarization and protect pregnancy. This study may provide a potential therapeutic strategy for miscarriage induced by inflammation.