Non-coding RNA regulating endometrial receptivity and its dysfunctions: a narrative review

Endometrial receptivity (ER) represents a transient, hormone-dependent phase during which the endometrium becomes competent to support embryo implantation. Beyond protein-coding genes, non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have emerged as central regulators of this transformation. These molecules coordinate gene expression networks that govern stromal decidualization, epithelial remodeling, angiogenesis, and cellular communication essential for implantation. Transcriptomic and multi-omics studies have revealed dynamic ncRNA expression patterns across the menstrual cycle and during the transition to endometrial receptivity, highlighting their mechanistic roles in modulating endometrial function. Dysregulated ncRNA networks are increasingly implicated in reproductive disorders such as endometriosis, adenomyosis, endometritis, uterine fibroids, polycystic ovary syndrome (PCOS), recurrent implantation failure (RIF), and recurrent pregnancy loss (RPL). Distinct ncRNA signatures identified in these conditions offer valuable insights into disease pathophysiology and hold promise as diagnostic and prognostic biomarkers. Circulating and extracellular vesicle derived ncRNAs further provide minimally invasive tools for assessing endometrial status and implantation potential. Advances in single-cell transcriptomics, integrative bioinformatics, and RNA-targeted therapeutics are expanding our understanding of ncRNA-regulated pathways and paving the way for precision diagnostics and targeted interventions in reproductive medicine. This graphical abstract illustrates the diverse classes and molecular functions of non-coding RNAs (miRNAs, lncRNAs, and circRNAs) in regulating endometrial receptivity and their dysregulation across major reproductive disorders including endometriosis, adenomyosis, RIF, RPL, and endometritis. Together, these ncRNA-mediated networks highlight emerging diagnostic and therapeutic avenues in reproductive medicine.