Abstract
Aim. This study aimed to assess seminal miRNA relationship with seminal apoptotic markers and oxidative stress (OS) in infertile men associated with varicocele (Vx). Methods. In all, 220 subjects were divided into the following groups: fertile normozoospermic men, fertile normozoospermic men with Vx, infertile oligoasthenoteratozoospermic (OAT) men without Vx, and infertile OAT men with Vx. They were subjected to history taking, clinical examination, and semen analysis. In their semen, the following were estimated: miRNA-122, miRNA-181a, and miRNA-34c5 using quantitative real-time PCR, apoptotic markers (BAX, BCL2) protein expression, and OS markers [malondialdehyde (MDA) and glutathione peroxidase (GPx)]. Results. The mean levels of seminal miRNA-122, miRNA-181a, and miRNA-34c5 were significantly reduced in infertile OAT men with Vx compared with other groups coupled with Vx grade and Vx bilaterality. Seminal miRNA-122, miRNA-181a, and miRNA-34c5 were positively correlated with sperm concentration, total sperm motility, sperm normal morphology, seminal GPx, and seminal BCL2 and negatively correlated with seminal MDA and seminal BAX. Conclusions. Seminal miRNA-122, miRNA-181a, and miRNA-34c5 are decreased in infertile OAT men with Vx associated with increased Vx grade and Vx bilaterality. In addition, they are positively correlated with sperm parameters and negatively correlated with OS, apoptotic markers.
Highlights
MicroRNAs are a family of small noncoding RNAs of 22 nucleotides that regulate posttranscriptional gene silencing through base pair binding to untranslated region of their target mRNAs [1]
Seminal miRNA-122, miRNA-181a, and miRNA-34c5, seminal glutathione peroxidase (GPx) enzyme, and seminal BCL2 were significantly reduced whereas seminal MDA and seminal BAX were significantly increased in infertile OAT men with Vx compared with other groups (Table 1, Figure 1)
Seminal miRNA-122, miRNA-181a, and miRNA-34c5 were significantly reduced in grade III Vx cases compared with other Vx grades and in bilateral Vx cases compared with unilateral Vx cases (Table 2)
Summary
MicroRNAs (miRNA) are a family of small noncoding RNAs of 22 nucleotides that regulate posttranscriptional gene silencing through base pair binding to untranslated region of their target mRNAs [1]. Several miRNAs are implicated in regulating B-cell differentiation and T-cell receptor signaling, whereas others are associated with inflammation, innate immune responses, and apoptosis [2]. MiRNAs were initially detected in the human spermatozoa by Ostermeier et al [3]. They may participate in the spermatogenesis process because many miRNAs are produced plentifully in male germ cells. Wang et al [4] speculated that seminal miRNAs, as minimal invasive biomarkers, could provide useful information about gene expression in the male reproductive system. Seminal miRNAs possessed immense potential for forensic body fluid identification being expressed in a tissue specific manner and being less prone to degradation [5]. Vx associated cases were verified to have increased seminal OS as well as seminal apoptotic markers [8,9,10]
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