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<p>Infertility affects ~ 15% of couples globally, with male factors contributing to ~ 50% of cases. Male infertility comes from a variety genetic, hormonal, environmental, and lifestyle factors. Yet, a large proportion of cases are idiopathic and have no identifiable cause. Recent advances highlight the critical role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression at the post-transcriptional level, in male reproductive health. miRNAs are pivotal in spermatogenesis, sperm maturation, and testicular function, influencing processes such as cell cycle regulation, apoptosis, and differentiation. Altered miRNA expression has been linked to many types of male infertility, such as oligozoospermia (low sperm count), asthenozoospermia (low motility), azoospermia(no sperm) and teratozoospermia(abnormal morphology). Notably, miRNAs like miR-34c, miR-21, and miR-449 play essential roles in germ cell proliferation, meiotic progression, and spermiogenesis, while others, such as miR-210 and miR-122, impact sperm motility and DNA integrity.</p><p>Their stability in biological fluids positions miRNAs as promising non-invasive biomarkers for diagnosing male infertility. miRNA-based diagnostics significantly reduce the need for invasive testicular biopsies in men with azoospermia, enabling earlier, less invasive, and more accurate identification of underlying spermatogenic defects. Furthermore, miRNA-targeted therapies hold promise for restoring spermatogenesis in select cases, potentially improving fertility outcomes for affected patients. Moreover, therapeutic approaches targeting miRNA pathways, including miRNA mimics and inhibitors, offer innovative solutions to restore reproductive function. However, challenges such as complex miRNA networks, delivery system inefficiencies, and inter-individual variability hinder clinical translation. The various functions of miRNAs in male infertility are highlighted in this review, along with their potential for diagnosis, prognosis, and treatment.</p>

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MicroRNA dysregulation in male infertility: Insights into mechanisms, biomarkers, and therapeutic strategies- review

  • 期刊论文

  • 发表日期：

    2025年10月13日

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  • Manoharan Shunmuga Sundram,
  • Sanjeeva Ready Nellapalli,
  • Radha Vembu,
  • Manjula Gopala Krishnan,
  • Vettriselvi Venkatesan,
  • Madhan Kalagara

摘要

Infertility affects ~ 15% of couples globally, with male factors contributing to ~ 50% of cases. Male infertility comes from a variety genetic, hormonal, environmental, and lifestyle factors. Yet, a large proportion of cases are idiopathic and have no identifiable cause. Recent advances highlight the critical role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression at the post-transcriptional level, in male reproductive health. miRNAs are pivotal in spermatogenesis, sperm maturation, and testicular function, influencing processes such as cell cycle regulation, apoptosis, and differentiation. Altered miRNA expression has been linked to many types of male infertility, such as oligozoospermia (low sperm count), asthenozoospermia (low motility), azoospermia(no sperm) and teratozoospermia(abnormal morphology). Notably, miRNAs like miR-34c, miR-21, and miR-449 play essential roles in germ cell proliferation, meiotic progression, and spermiogenesis, while others, such as miR-210 and miR-122, impact sperm motility and DNA integrity.

Their stability in biological fluids positions miRNAs as promising non-invasive biomarkers for diagnosing male infertility. miRNA-based diagnostics significantly reduce the need for invasive testicular biopsies in men with azoospermia, enabling earlier, less invasive, and more accurate identification of underlying spermatogenic defects. Furthermore, miRNA-targeted therapies hold promise for restoring spermatogenesis in select cases, potentially improving fertility outcomes for affected patients. Moreover, therapeutic approaches targeting miRNA pathways, including miRNA mimics and inhibitors, offer innovative solutions to restore reproductive function. However, challenges such as complex miRNA networks, delivery system inefficiencies, and inter-individual variability hinder clinical translation. The various functions of miRNAs in male infertility are highlighted in this review, along with their potential for diagnosis, prognosis, and treatment.