Guipi Tang Regulates Metabolic Reprogramming at the Maternal-FetalInterface in a Mouse Model of Unexplained Recurrent SpontaneousAbortion

Background: Guipi Tang has been used as a therapeutic agent in many diseases because of its function of balancing the immune state; however, there are no reports concerning the effects of Guipi Tang on unexplained Recurrent Spontaneous Abortion (RSA). Objective: The present experiment was designed to investigate the effects of Guipi Tang on the pregnancy outcomes of the RSA mouse as well as explore its underlying mechanism. results: In the RSA group, the rate of absorbed embryo was statistically higher than control group. Whereas, Guipi Tang administration showed a protective effect on spontaneous abortion in RSA mice. The morphology of maternal-fetal interface was improved by Guipi Tang. The RSA + Guipi Tang group demonstrated remarkably augmented expression levels of Arginase-1, CD206+ and IL-10, as well as diminished level of IL-1β compared with RSA group. Methods: Thirty female CBA/J mice aging 8-10 weeks were randomly categorized into 3 groups and copulated with BALB/c mice aging 8-10 weeks (BALB/c×CBA/J) as control group (n=10), or copulated with DBA/2 mice aging 8-10 weeks (DBA/2×CBA/J) as RSA model (n=10), or DBA/2×CBA/J mice aging 8-10 weeks with Guipi Tang administration as RSA + Guipi Tang group (n=10). The number of resorbed embryos was counted on 13.5 days after gestation. Furthermore, histological analysis of placental and decidual tissues was performed. Immunohistochemistry and western blotting were also employed to detect protein expressions of Arginase-1, CD206+(M2-phenotype macrophage), IL-1β, and IL10 in the placental and decidual tissues. Results: In the RSA group, the rate of absorbed embryos was statistically higher than that of the control group. At the same time, the Guipi Tang administration showed protective effects against embryo loss in RSA mice. The morphology of the maternal-fetal interface was improved by Guipi Tang. The RSA + Guipi Tang group demonstrated remarkably augmented expression of Arginase-1, CD206+, and IL-10, as well as the diminished expression of IL-1β, compared with the RSA group. Discussion: Immune cell metabolic reprogramming could be one of the vital targets for improving the pregnancy outcomes of RSA. Besides, the Guipi Tang administration is beneficial for maintaining immune tolerance at the maternal-fetal interface. These data provide a new perspective for RSA treatment. Conclusion: Guipi Tang administration demonstrates protective effects on pregnancy outcomes in the RSA mouse, at least partly via regulating glutamine metabolism, thereby balancing macrophage polarization at the maternal-fetal interface.