# MicroRNAs Regulating Oxidative Stress in Human Fertility: A Narrative Review of Mechanistic Insights and Clinical Potential

## TL;DR

This review explores how microRNAs and oxidative stress contribute to infertility in both men and women, highlighting their potential as diagnostic and therapeutic tools.

## Contribution

The paper provides a comprehensive analysis of miRNA regulation of oxidative stress in human fertility, emphasizing their clinical potential.

## Key findings

- miRNAs like miR-21, miR-34a, and miR-155 are dysregulated in male infertility conditions such as varicocele.
- miRNAs including miR-132-3p and let-7 regulate redox-sensitive pathways affecting female reproductive disorders like PCOS and POI.
- Altered miRNA expression correlates with poor reproductive outcomes, suggesting their potential as biomarkers and therapeutic targets.

## Abstract

Human infertility represents a multifaceted condition, with oxidative stress (OS) and microRNAs (miRNAs) emerging as key contributors to its pathophysiology. This comprehensive review explores the complex interplay between reactive oxygen species (ROS) and miRNAs in male and female reproductive dysfunctions. ROS overproduction damages DNA, lipids, and proteins, impairing sperm quality and oocyte maturation. In males, OS is a leading cause of infertility, especially in conditions like varicocele, where key miRNAs such as miR-21, miR-34a, and miR-155 are dysregulated. In females, oxidative imbalance affects granulosa cells and follicular environments in disorders such as PCOS, premature ovarian insufficiency (POI), and endometriosis. Several miRNAs (e.g., miR-132-3p, let-7, miR-642a-5p) regulate mitochondrial function, steroidogenesis, and apoptosis through redox-sensitive signaling pathways (PI3K/Akt, NF-κB, FOXO1). Their altered expression in ovarian and seminal environments correlates with poor reproductive outcomes. Emerging evidence supports their potential role as diagnostic biomarkers and therapeutic targets, although most findings are based on animal models or in vitro studies. This review highlights the therapeutic potential of miRNA modulation and calls for further clinical research to validate miRNA-based interventions. Ultimately, understanding the miRNA–OS nexus offers promising avenues for improving diagnosis, prognosis, and treatment of infertility across both sexes.