NAD + Metabolism Maintains the Homeostasis of Decidual Macrophages in Early Pregnancy

mice significantly ameliorated the adverse pregnancy outcome. Genetic and pharmacological interference of NAMPT disrupted the differentiation of M1 macrophages. Mechanically, deficiency of NAMPT inhibited gasdermin D (GSDMD) cleavage independently from canonical pyroptosis. The cleaved N-terminal fragment of GSDMD functioned as a stimulus to activate the NF-κB pathway and subsequently promoted TNF-α transcription by phospho-P65 (S536). NMN replenishment ameliorated the dysregulation of M1 macrophage differentiation, the infiltration of trophoblasts, and fetal loss. Our study reveals an NAMPT-associated immunopathogenesis of early pregnancy loss and provides a new idea for the therapeutic strategy for RSA patients.