Towards a More Comprehensive Picture of the MicroRNA-23a/b-3p Impact on Impaired Male Fertility

The expression levels of various genes involved in human spermatogenesis are influenced by microRNAs (miRNAs), specifically microRNA-23a/b-3p. While certain genes are essential for spermatogenesis and male germ cell function, the regulation of their expression remains unclear. This study aimed to in...

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Bibliographic Details
Main Authors: Lea Simone Becker, Mohammad A. Al Smadi, Hanna Koch, Hashim Abdul-Khaliq, Eckart Meese, Masood Abu-Halima
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/12/6/800
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Summary:The expression levels of various genes involved in human spermatogenesis are influenced by microRNAs (miRNAs), specifically microRNA-23a/b-3p. While certain genes are essential for spermatogenesis and male germ cell function, the regulation of their expression remains unclear. This study aimed to investigate whether microRNA-23a/b-3p targets genes involved in spermatogenesis and the impact of this targeting on the expression levels of these genes in males with impaired fertility. In-silico prediction and dual-luciferase assays were used to determine the potential connections between microRNA-23a/b-3p overexpression and reduced expression levels of 16 target genes. Reverse transcription-quantitative PCR (RT-qPCR) was conducted on 41 oligoasthenozoospermic men receiving infertility treatment and 41 age-matched normozoospermic individuals to verify the lower expression level of target genes. By employing dual-luciferase assays, microRNA-23a-3p was found to directly target eight genes, namely <i>NOL4, SOX6, GOLGA6C, PCDHA9, G2E3, ZNF695, CEP41</i>, and <i>RGPD1</i>, while microRNA-23b-3p directly targeted three genes, namely SOX6, <i>GOLGA6C</i>, and <i>ZNF695</i>. The intentional alteration of the microRNA-23a/b binding site within the 3′ untranslated regions (3′UTRs) of the eight genes resulted in the loss of responsiveness to microRNA-23a/b-3p. This confirmed that <i>NOL4, SOX6, GOLGA6C, PCDHA9</i>, and <i>CEP41</i> are direct targets for microRNA-23a-3p, while <i>NOL4, SOX6</i>, and <i>PCDHA9</i> are direct targets for microRNA-23b-3p. The sperm samples of oligoasthenozoospermic men had lower expression levels of target genes than age-matched normozoospermic men. Correlation analysis indicated a positive correlation between basic semen parameters and lower expression levels of target genes. The study suggests that microRNA-23a/b-3p plays a significant role in spermatogenesis by controlling the expression of target genes linked to males with impaired fertility and has an impact on basic semen parameters.
ISSN:2079-7737