Abstract
Our previous research suggested that an integrated analysis of microRNA (miRNA) and messenger RNA (mRNA) expression is helpful to explore miRNA-mRNA interactions and to uncover the molecular mechanisms of male infertility. In this study, microarrays were used to compare the differences in the miRNA and mRNA expression profiles in the testicular tissues of severe oligozoospermia (SO) patients with obstructive azoospermia (OA) controls with normal spermatogenesis. Four miRNAs (miR-1246, miR-375, miR-410, and miR-758) and six mRNAs (SLC1A3, PRKAR2B, HYDIN, WDR65, PRDX1, and ADATMS5) were selected to validate the microarray data using quantitative real-time PCR. Using statistical calculations and bioinformatics predictions, we identified 33 differentially expressed miRNAs and 1,239 differentially expressed mRNAs, among which one potential miRNA-target gene pair, miR-34c-3p and PLCXD3 (Phosphatidylinositol-Specific Phospholipase C, X Domain Containing 3), was identified. Immunohistochemical analysis indicated that PLCXD3 was located within the germ cells of the mouse and human testis. Moreover, we found that miR-34c-3p was able to decrease PLCXD3 expression in mouse (GC-1 and TM4) and human (NCM460) cell lines, presumably indicating the possibility that miR-34c-3p acts as an intracellular mediator in germinal lineage differentiation. Notably, we reported the expression of the PLCXD3 protein in a man with normal spermatogenesis and the lack of the PLCXD3 protein in a man with SO. Therefore, the identified miRNA and mRNA may represent a potentially novel molecular regulatory network and therapeutic targets for the study or treatment of SO, which might provide a better understanding of the molecular basis of spermatogenesis dysfunction.
Highlights
Infertility is global health problem, and the increasing trend in infertility deserves more scientific attention
With the aim of elucidating the molecular mechanisms underlying severe oligozoospermia (SO) at the transcriptome level, we first compared the miRNAmRNA profiles of SO to those of obstructive azoospermia (OA) using microarrays and discovered the direct messenger RNA (mRNA) targets of the miRNAs based on the anti-correlation data of the differentially expressed miRNAs and mRNAs
The results showed that there was a significant difference in the mRNA and miRNA expression profiles between the two groups when we compared the transcriptome data from the SO and OA samples
Summary
Infertility is global health problem, and the increasing trend in infertility deserves more scientific attention. There is no consensus definition of severe oligozoospermia (SO), a sperm concentration of 5 × 106/mL was chosen as the detection limit for case selection, based on a detailed review of the recent literature on the evaluation of male fertility [2,3,4]. It www.impactjournals.com/oncotarget is recognized that men with very low sperm counts have a higher incidence of Y-chromosome microdeletions (up to 17%) [5]. The genetic causalities of most cases of low sperm count have not been elucidated
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