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Association of Circular RNAs with Sperm Fertility Potential: Implications for Male Infertility Diagnosis

Sara Esmaeilzadeh1, Fatemeh Ghasemian1, Fatemeh Aziziyan2

  • 1Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.

Journal of Reproduction & Infertility
|April 27, 2026
PubMed

Insights

Circular RNAs (circRNAs) in human semen are linked to sperm quality. These biomarkers show altered expression in relation to sperm morphology, motility, and concentration, suggesting their role in male fertility.

Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Biomarker Discovery

Background:

  • Circular RNAs (circRNAs) are implicated in spermatogenesis.
  • Four specific circRNAs (STK31-hsa-circ-0133980, LRWD1-hsa-circ-0003327, circRNF17, and circBRDT) were identified in human semen.
  • Their association with sperm parameters requires further investigation.

Purpose of the Study:

  • To evaluate the relationship between specific circRNAs and sperm parameters in men.
  • To assess the expression levels of circRNAs in relation to genes involved in apoptosis and protamination.
  • To determine the potential of circRNAs as biomarkers for male fertility.

Main Methods:

  • Analysis of 45 semen samples categorized into normozoospermia and various infertility groups (asthenozoospermia, oligozoospermia, teratozoospermia, oligoasthenoteratozoospermia).
  • Quantification of four circRNAs and apoptosis/protamination-related genes (BCL2, BAX, Caspase3, PRM1, PRM2) using real-time polymerase chain reaction (RT-PCR).
  • Assessment of sperm quality using triple staining and eosin-nigrosin staining; statistical analysis via one-way ANOVA.

Main Results:

  • Significant correlations were observed between circRNA expression levels and sperm morphology (all circRNAs, p<0.05), motility (circRNF17 and STK31, p<0.01), and concentration (circBRDT, p<0.05).
  • Increased apoptosis and abnormal protamination (upregulation of BAX, Caspase 3; downregulation of BCL2, PRM1&2) were noted in infertile groups compared to normozoospermic controls (p<0.001).
  • Distinct circRNA profiles were found in semen samples with varying sperm quality.

Conclusions:

  • CircRNA levels differ based on sperm quality, indicating their functional relevance.
  • These findings highlight the potential utility of circRNAs as novel biomarkers for assessing male fertility and sperm function.
Abstract

Keywords:
ApoptosisCircular RNAsFertilityProtaminationSperm

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