Trained immunity in pregnancy: Impact on maternal-fetal outcomes and mechanistic insights

Trained immunity, defined as the epigenetic and metabolic reprogramming of innate immune cells that shapes their subsequent responses, has emerged as a key paradigm in reproductive immunology. In pregnancy, trained immunity can act as a "double-edged sword." Beneficial training of decidual NK cells and macrophages promotes vascular remodeling, tissue repair, and host defense, thereby supporting implantation and placental development. Conversely, dysregulated training triggered by hypoxia, metabolic stress, or infection may sustain chronic inflammation and contribute to preeclampsia, fetal growth restriction, and recurrent pregnancy loss. In this review, we summarize current evidence for both protective and pathogenic roles of trained immunity during pregnancy, highlight the underlying molecular mechanisms, and discuss key research gaps. Considering pregnancy complications from the perspective of trained immunity may provide new insights into pathogenesis and suggest opportunities for biomarker discovery and targeted interventions.