MicroRNA expression profiles in human testicular tissues of infertile men with different histopathologic patterns

The role of epigenetics in idiopathic male infertility

“…Seven miRNAs that were significantly decreased in NOA patients but markedly increased in asthenozoospermia patients were found to be miR-34c-5p, miR-122, miR-146b-5p, miR-181a, miR-374b, miR-509-5p, and miR-513a-5p (Table 2). Although testicular tissues of the patients were not analyzed in this study, miR34c-5p, miR-122, miR-181a, and miR-509-5p have also been shown to be decreased in testicular tissues of NOA patients in several different studies, confirming the utility of these miRNAs as noninvasive diagnostic tools for NOA [99,107,108,110]. Interestingly, in patients with asthenozoospermia, miR-122 has later been reported to be downregulated in spermatozoa samples [105], by contrast with its abovementioned upregulation observed in seminal plasmas [102].…”

“…Therefore, low expression of these miRNA clusters may explain increased apoptosis observed in the testes of NOA patients [99]. A more recent and comprehensive miRNA microarray analysis of testicular tissue samples from 40 azoospermic men of different histopathologic subgroups has revealed a total of 311 differentially expressed miRNAs when compared to samples with normal spermatogenesis [107]. The numbers of differentially expressed miRNAs were 197, 68, and 46 for SCO, mixed atrophy (MA), and germ cell arrest (GA) groups, respectively, in comparison with normal spermatogenesis (Table 2).…”

“…Among all tested groups, the highest fold changes were observed with only seven miRNAs, all of them downregulated including miR-449 family members (miR-449a, miR-449b*), miR-34 family members (miR-34b*, miR-34b, miR-34c-5p), miR-517b, and miR-129-3p. Notably, potential targets of these miRNAs are involved in spermatogenesis process, apoptosis, cell proliferation, differentiation, and testicular development [107]. Of special interest are miR-34b and miR-34c, which were previously shown to target deleted in azoospermia-like (DAZL) transcript that is essential for gametogenesis in mice [115,116].…”

“…Given the crucial roles of estrogen receptor-α and -β in maintenance of male reproductive tract function, sperm metabolism and Sertoli cell proliferation, it would not be surprising if there exists a miRNA-based mechanism for downregulation of these two receptors in infertile men [118,119]. Using qRT-PCR, a validation study has tested the potential of a set of five differentially expressed miRNAs selected from the two aforementioned miRNA microarray analyses [105,107], to be used as biomarkers for the assessment of male infertility [108]. Spermatozoa from 80 subfertile (mostly oligospermic and oligoasthenospermic) men and testicular tissues from 40 men with non-obstructive azoospermia were analyzed along with their appropriate controls, and with the exception of miR-429, the expressions of all other four miRNAs (miR-34b*, miR-34b, miR-34c-5p, miR-122) were found to be decreased in both tested groups [108].…”

Dramatic Changes in 67 miRNAs During Initiation of First Wave of Spermatogenesis in Mus musculusTestis: Global Regulatory Insights Generated by miRNA-mRNA Network Analysis1

“…The miRNAs constitute an integral part of the posttranscription regulatory network that governs variable gene expression underlying male germ cell differentiation [10]. They are differentially expressed during normal mammalian spermatogenesis [11][12][13][14][15][16][17] and in spermatogenic dysfunction in human [18,19]. It was reported that the mouse miRNAs miR-221, miR-203, and miR-34b-5p were specific for spermatogonial stem cells, premeiotic cells, and meiotic cells, respectively [20].…”