精索静脉曲张患者精子 hsa-mir-145-5p 和 MLH1 表达、精液氧化应激与精子 DNA 碎片化的研究。

Investigation of sperm hsa-mir-145-5p and MLH1 expressions, seminal oxidative stress and sperm DNA fragmentation in varicocele.

机构信息

Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, 55139, Turkey.

Graduate Institute, Department of Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey.

出版信息

Mol Biol Rep. 2024 Apr 29;51(1):588. doi: 10.1007/s11033-024-09534-1.

DOI:10.1007/s11033-024-09534-1

PMID:38683237

Abstract

BACKGROUND

Mechanisms by which varicocele causes infertility are not clear and few studies have reported that some miRNAs show expression alterations in men with varicocele. Recently, sperm promoter methylation of MLH1 has been shown to be higher in men diagnosed with varicocele. This study aimed to assess the potential effects of miR-145, which was determined to target MLH1 mRNA in silico on sperm quality and function in varicocele.

METHODS

Sperm miR-145 and MLH1 expressions of six infertile men with varicocele (Group 1), nine idiopathic infertile men (Group 2), and nine fertile men (control group) were analyzed by quantitative PCR. Sperm DNA fragmentation was evaluated by TUNEL and the levels of seminal oxidative damage and total antioxidant capacity were analyzed by ELISA.

RESULTS

Our results have shown that sperm expression of miR-145 was decreased in Group 1 compared to Group 2 (P = 0.029). MLH1 expression was significantly higher in Group 2 than the controls (P = 0.048). Total antioxidant level and sperm DNA fragmentations of Group 1 and Group 2 were decreased (P = 0.001 and P = 0.011, respectively). Total antioxidant capacity was positively correlated with sperm concentration (ρ = 0.475, P = 0.019), total sperm count (ρ = 0.427, P = 0.037), motility (ρ = 0.716, P < 0.0001) and normal morphological forms (ρ = 0.613, P = 0.001) and negatively correlated with the seminal oxidative damage (ρ=-0.829, P = 0.042) in varicocele patients.

CONCLUSION

This is the first study investigating the expressions of sperm miR-145 and MLH1 in varicocele patients. Further studies are needed to clarify the potential effect of miR-145 on male fertility.

摘要

背景

精索静脉曲张导致不育的机制尚不清楚，少数研究报道精索静脉曲张患者的一些 miRNAs 表达发生改变。最近，已证实精索静脉曲张患者精子启动子 MLH1 的甲基化水平较高。本研究旨在评估 miR-145 在精索静脉曲张中的潜在作用，该 miRNA 在计算机上被确定为靶向 MLH1 mRNA。

方法

通过定量 PCR 分析 6 名精索静脉曲张不育男性（第 1 组）、9 名特发性不育男性（第 2 组）和 9 名正常生育男性（对照组）的精子 miR-145 和 MLH1 的表达。通过 TUNEL 评估精子 DNA 碎片化，通过 ELISA 分析精液氧化损伤水平和总抗氧化能力。

结果

与第 2 组相比，第 1 组精子 miR-145 表达降低（P=0.029）。第 2 组 MLH1 表达明显高于对照组（P=0.048）。第 1 组和第 2 组的总抗氧化水平和精子 DNA 碎片化均降低（P=0.001 和 P=0.011）。总抗氧化能力与精子浓度（ρ=0.475，P=0.019）、总精子计数（ρ=0.427，P=0.037）、活力（ρ=0.716，P<0.0001）和正常形态（ρ=0.613，P=0.001）呈正相关，与精索静脉曲张患者的精液氧化损伤呈负相关（ρ=-0.829，P=0.042）。