Global analysis in non-obstructive azoospermic testis identifies miRNAs critical to spermatogenesis

Abstract

Background The etiology of male infertility accompanied by azoospermia is largely unknown especially at the molecular level. Identifying the global expression profile of dysregulated microRNAs (miRNAs) in male infertility would be useful to achieve a more profound understanding of pathogenesis. Methods Small RNA sequencing was performed on testicular tissues of 10 nonobstructive azoospermic patients with Sertoli cell only syndrome (SCOS) and those of 8 obstructive azoospermic individuals. The expression of 4 dysregulated miRNAs was validated by quantitative Real-Time polymerase chain reaction, confirming the results obtained by sequencing analysis. Bioinformatics analysis was utilized to discover novel miRNAs as well as to identify the main pathways impaired in spermatogenic failure. Results A total of 149 miRNAs were detected to be differentially expressed in the Sertoli cell only syndrome group in comparison with the obstructive azoospermia group. Of these, 13 miRNAs were novel. Bioinformatics analysis suggested that the altered miRNAs were substantially involved in pathways related to spermatogenesis. Conclusions Our study introduces novel miRNAs with emphasis on the crucial role of miRNAs in idiopathic Sertoli cell only syndrome, suggesting potential targets for employing molecular therapeutic strategies in spermatogenic failure treatment.

Identification of ITPR1 gene as a novel target for hsa-miR-34b-5p in non-obstructive azoospermia: a Ca2+/apoptosis pathway cross-talk

“…Therefore, the miRNA/mRNA axis has been considered an effective functional marker in various biological processes including spermatogenesis 5 – 8 . In particular, several studies have indicated that the miR-34b family has a crucial role as a regulatory factor on genes involved in spermatogenesis 9 – 11 . This family of miRNAs is highly conserved among species that involve different biological procedures including differentiation, growth, cell cycle, spermatogenesis, and apoptosis.…”

On The Origin of Speciation

“…5% of men have infertility, of which 75% are said to have idiopathic sperm dysfunction of unknown cause (Okada et al, 2008). The miR888 cluster was downregulated in the testis of non-obstructive azoospermia (NOA) patients compared to obstructive azoospermia patients (Piryaei et al, 2022). Misexpression of target genes due to Fx-mir downregulation is thought to impair spermatogenesis, and Fx-mir and its target genes may be candidates for DMI model genes.…”