Age-related changes in lncRNA expression in sperm

Qiao Zhou; Guangyao Li; Hui Ji; Juan Ji; Zhonghui Ling; Jingwen Sun; Hui Ding; Junqiang Zhang; Xiufeng Ling; Xiaoning Chen; Lu Xu

doi:10.21037/tau-2025-31

Age-related changes in lncRNA expression in sperm

Transl Androl Urol. 2025 May 30;14(5):1408-1417. doi: 10.21037/tau-2025-31. Epub 2025 May 27.

Authors

Qiao Zhou^#¹, Guangyao Li^#¹, Hui Ji¹, Juan Ji¹, Zhonghui Ling¹, Jingwen Sun¹, Hui Ding¹, Junqiang Zhang¹, Xiufeng Ling¹, Xiaoning Chen¹, Lu Xu¹

Affiliation

¹ Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Background: Over the past few decades, the age of parenthood has become increasingly delayed. With increasing age, offspring health may be affected; these effects can include an increased risk of genetic disorders and diseases related to neurodevelopment and cognitive function, such as autism and schizophrenia. Long noncoding RNAs (lncRNAs) play important roles in reproductive processes and epigenetics, regulating gene expression through epigenetic modifications, transcriptional regulation, and posttranscriptional control. Abnormal lncRNA expression is associated with the occurrence of various diseases. Currently, no research on alterations in the lncRNA expression profile in sperm from older fathers is available. This study aims to investigate the changes in lncRNA expression profiles in sperm from older fathers and explore their potential impact on offspring health.

Methods: A total of six volunteers were included; three volunteers (≥40 years old) were assigned to the study group, and the remaining volunteers (<40 years old) were assigned to the control group. High-throughput sequencing was used to analyze lncRNA and messenger RNA (mRNA) expression in sperm samples.

Results: The analysis revealed significant differences in the expression of 8,154 lncRNAs between the two groups: these lncRNAs consisted of 4,031 downregulated lncRNAs and 4,123 upregulated lncRNAs. In addition, 2,930 significantly differentially expressed mRNAs were identified; among these mRNAs, 1,155 were upregulated, and 1,775 were downregulated. Functional enrichment analysis of the differentially expressed lncRNAs and mRNAs revealed roles in pathways such as metabolism, RNA transport, and protein hydrolysis. Through comprehensive analysis of the lncRNA-mRNA network, we constructed a network of 178 co-expressed lncRNAs and mRNAs.

Conclusions: Spermatogenesis is a complex biological process (BP) regulated by various factors, including lncRNAs. This study provides preliminary data to help understand changes in lncRNA expression in the sperm of older fathers and may provide insight for future research on the health of offspring from older fathers.

Keywords: Advanced paternal age (APA); human reproduction; long noncoding RNAs (lncRNAs); offspring health; sperm.