Integrated analysis of autophagy-related lncRNAs and oxidative DNA damage reveals molecular signatures of severe sperm abnormalities.

IF 2.8 3区医学 Q2 GENETICS & HEREDITY

Journal of Assisted Reproduction and Genetics Pub Date : 2026-09-16 DOI:10.1007/s10815-026-04005-x

Ebru Etem Önalan, Sebnem Nur Keke Urhan, Ahmet Karakeci, Berna Ozdem, Ilay Buran Kavuran

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引用次数: 0

Abstract

Purpose: Autophagy is a critical intracellular degradation pathway involved in cellular homeostasis and spermatogenesis. Long noncoding RNAs (lncRNAs) regulate autophagy-related signaling; however, their role in male infertility remains unclear. This study aimed to evaluate the association between autophagy-related lncRNAs, oxidative DNA damage, and sperm abnormalities in infertile men.

Methods: A total of 120 men were included: 30 fertile controls, 30 with asthenospermia (AS), 30 with teratospermia (TS), and 30 with oligoasthenoteratozoospermia (OATS). Expression levels of autophagy-related lncRNAs and protein-coding genes were quantified using real-time PCR. LC3 protein expression was assessed by Western blot, and sperm 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured by ELISA. Statistical analyses included ANOVA, correlation analysis, and receiver operating characteristic (ROC) curve analysis.

Results: Autophagy-related lncRNAs (H19, HOTAIR, MALAT1, NBR2, HULC, and ROR) and key autophagy markers (ATG7 and LC3) were significantly upregulated predominantly in the OATS group compared with controls and other groups (p < 0.05). LC3 protein levels were also significantly increased in OATS. Sperm 8-OHdG levels were significantly elevated in both AS and OATS groups. Correlation analyses revealed significant associations between hormone levels (FSH, LH, and prolactin) and lncRNA expression, particularly in the OATS group. ROC analysis demonstrated moderate discrimination for OATS versus other groups (AUC = 0.754) and excellent discrimination for OATS versus controls (AUC = 0.902).

Conclusion: Dysregulation of autophagy-related lncRNAs and increased oxidative DNA damage are strongly associated with severe sperm abnormalities. The observed molecular alterations may represent either contributors to sperm dysfunction or adaptive responses to oxidative stress. Combined evaluation of these markers showed promising discriminatory performance, although validation in larger independent cohorts is required before clinical application.

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对自噬相关lncrna和氧化DNA损伤的综合分析揭示了严重精子异常的分子特征。

目的：自噬是参与细胞稳态和精子发生的重要细胞内降解途径。长链非编码rna （lncRNAs）调控自噬相关信号传导；然而，它们在男性不育中的作用尚不清楚。本研究旨在评估不育男性自噬相关lncRNAs、氧化DNA损伤和精子异常之间的关系。方法：共纳入120例男性：正常对照30例，弱精子症（AS） 30例，畸形精子症（TS） 30例，少弱异精子症（OATS） 30例。实时荧光定量PCR检测自噬相关lncrna和蛋白编码基因的表达水平。Western blot检测LC3蛋白表达，ELISA检测精子8-羟基-2′-脱氧鸟苷（8-OHdG）水平。统计分析包括方差分析、相关分析和受试者工作特征（ROC）曲线分析。结果：自噬相关lncrna （H19、HOTAIR、MALAT1、NBR2、HULC和ROR）和关键自噬标志物（ATG7和LC3）在燕麦组显著上调，显著高于对照组和其他组(p结论：自噬相关lncrna失调和氧化DNA损伤增加与严重精子异常密切相关。观察到的分子改变可能代表精子功能障碍的贡献者或对氧化应激的适应性反应。尽管在临床应用之前需要在更大的独立队列中进行验证，但对这些标记物的综合评估显示出有希望的歧视性表现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Assisted Reproduction and Genetics 医学-妇产科学

CiteScore

5.70

自引率

9.70%

发文量

286

审稿时长

1 months

期刊介绍： The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.