Gene regulation by non-Coding RNAs in infertility: a mechanistic review

Infertility is a significant global health issue affecting millions of couples, with noncoding RNAs (ncRNAs) emerging as pivotal regulators in reproductive biology. This review explores the roles of various ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and circular RNAs (circRNAs) in male and female infertility. These ncRNAs modulate critical processes such as spermatogenesis, oogenesis, follicular development, and embryo implantation through mechanisms like post-transcriptional regulation, chromatin remodeling, and transposon silencing. Dysregulation of ncRNAs is linked to reproductive disorders such as azoospermia, polycystic ovarian syndrome (PCOS), and endometriosis, highlighting their potential as diagnostic biomarkers. For instance, seminal plasma miRNAs and follicular fluid-derived ncRNAs offer non-invasive tools for assessing fertility status. Additionally, ncRNAs hold therapeutic promise, with synthetic mimics and inhibitors being explored to restore fertility. However, challenges such as variability in ncRNA expression, lack of standardized protocols, and the need for extensive clinical validation hinder their translation into clinical practice. This review synthesizes current knowledge on ncRNA mechanisms in infertility, underscores their biomarker potential, and discusses innovative therapeutic strategies, while addressing the obstacles to their clinical application.

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