Seminal exosomes and miRNA-mediated regulation of SRD5A2 in male infertility: An observational study

Abstract

Objective: To investigate the levels of seminal plasma exosomes and the expression of the SRD5A2 gene in Iraqi men with different types of male infertility (asthenozoospermia, oligozoospermia, and azoospermia), and to explore the regulatory role of selected microRNAs (miRNAs) in the modulation of SRD5A2 gene expression.

Methods: A total of 90 male participants were categorized into four groups: asthenozoospermia (n=24), oligozoospermia (n=24), azoospermia (n=18), and normozoospermia (n=24). Seminal plasma exosome levels were quantified using ELISA. RNA, including miRNAs, was extracted, followed by cDNA synthesis. The expression of SRD5A2 mRNA and five selected miRNAs (miR-6090, hsa-miR-5189-5p, miR-23a-5p, miR-1914-3p, and miR-4540) was evaluated using qRT-PCR. Correlation analyses were conducted between exosome levels, miRNA expression, and SRD5A2 expression.

Results: Infertile men exhibited significantly lower seminal exosome levels than normozoospermic men (P<0.01). The expression of SRD5A2 mRNA was decreased in asthenozoospermic and oligozoospermic men but elevated in azoospermic men. Elevated levels of hsa-miR-5189-5p, miR-6090, and miR-23a-5p were observed in infertile groups. Correlation analysis revealed a significant negative relationship between these miRNAs and SRD5A2 expression in asthenozoospermic and oligozoospermic men, but a positive correlation in azoospermic men. Exosome levels were also significantly correlated with the expression of these miRNAs, suggesting their role as molecular carriers in regulating gene expression.

Conclusions: This study highlights the potential role of seminal exosomes and specific miRNAs in regulating SRD5A2 gene expression among infertile men. The altered levels of exosomes and dysregulated miRNA expression, particularly hsa-miR-5189-5p and miR-6090, may serve as novel biomarkers for the diagnosis and management of male infertility. Further research is warranted to validate these findings and explore their therapeutic implications.

Keywords

miRNA regulation / 5α-reductase type 2 / Exosomal biomarkers / Male infertility / Non-coding RNAs in infertility

Conflict of interest statement

The authors declare that they have no competing interests.

Funding

The study receives no extramural funding.

Data availability statement

All data in this manuscript are available.

Authors’ contributions

Adnan F. AL-Azaawie performed conceptualization, methodology design, sample collection, experimental analysis, data interpretation, and manuscript drafting. Mousa Jasim Mohammed performed laboratory work including RNA extraction, qRT-PCR assays, statistical analysis, and result visualization. Ahmed AbdulJabbar Suleiman contributed to supervision, bioinformatics analysis of miRNA targets, critical revision of the manuscript, correspondence with the journal, and final approval of the version to be published. All authors have read and approved the final manuscript.

Publisher’s Note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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