Chen Zhou, Xiaoqing Zhu, Lijun Guan, Zhiqian Xu, Xiangbin You, Xiaoxia Li, Youbing Yang
Embryo implantation is a highly selective and hormonally regulated event, critically dependent on endometrial receptivity and the molecular microenvironment of uterine fluid (UF). UF is actively secreted by endometrial glands and epithelial cells and comprises proteins, metabolites, hormones, and extracellular vesicles (EVs) carrying miRNAs, lncRNAs, and regulatory proteins. These components coordinate embryo development, trophoblast invasion, angiogenesis, and maternal–fetal immune tolerance. Dysregulation of UF composition is increasingly implicated in reproductive disorders, including recurrent implantation failure, unexplained infertility, endometriosis, adenomyosis, and polycystic ovary syndrome, highlighting its potential as a noninvasive biomarker of endometrial function. Despite advances, challenges remain in standardizing UF sampling, addressing temporal and inter-individual variability, and elucidating upstream regulatory networks. Integrative multi-omics analyses, functional organoid–embryo models, and longitudinal clinical studies are essential to translate UF insights into predictive diagnostics and therapeutic strategies, ultimately improving implantation success and reproductive outcomes.