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This review proposes a unified barrier defense\u2013tolerance framework to explain how reproductive success depends on the coordinated integration of epithelial and mucus barriers, antimicrobial peptides, complement, tissue\u2010resident innate immune cells, pattern\u2010recognition receptor signaling, microbial ecology, and endocrine\u2013metabolic regulation across the female and male reproductive tracts and the maternal\u2013fetal interface. We summarize how Toll\u2010like receptors, NOD\u2010like receptors, RIG\u2010I\u2010like receptors, and cGAS\u2013STING pathways shape early reproductive events, including gamete quality control, sperm transit, implantation, placentation, and antiviral defense, and how tightly constrained physiological inflammation supports tissue remodeling, whereas excessive or unresolved activation contributes to infertility, recurrent pregnancy loss, preeclampsia, fetal growth restriction, and preterm birth. We further examine microbiota\u2013host interactions in reproduction, emphasizing that evidence is strongest for cervicovaginal communities, while endometrial, placental, and male genital microbiota findings require more cautious interpretation because of low\u2010biomass sampling, contamination risk, and limited reproducibility. Beyond local microbial niches, gut\u2010derived metabolites emerge as important regulators of immune tone and barrier function in reproductive tissues. We also discuss downstream effector mechanisms, including inflammasomes, regulated cell death, extracellular vesicles, and soluble innate mediators, and evaluate their translational relevance for biomarker development and targeted intervention. Overall, reproductive disorders are best viewed as systems\u2010level outcomes of disturbed interactions among host barriers, innate sensing thresholds, microbial signals, and metabolic context, providing a conceptual basis for future multi\u2010omics and mechanism\u2010driven reproductive immunology.<\/jats:p>","DOI":"10.1096\/fj.202601196r","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:36:26Z","timestamp":1776090986000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Innate Immunity and Microbial Recognition in Reproduction: From Barrier Defense to Maternal\u2013Fetal Tolerance"],"prefix":"10.1096","volume":"40","author":[{"given":"Xianlin","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Infectious Disease Tongde Hospital of Zhejiang Province  Hangzhou Zhejiang 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