# Identification of hub genes associated with decreased fertility in male mice of advanced paternal age

**Authors:** Yang Gao, Ting Zhang, Yan Wang, Haitao Lv, Xiangming Yan, Longlong Fu, Ying Liu

PMC · DOI: 10.3389/fcell.2025.1520387 · Frontiers in Cell and Developmental Biology · 2025-04-04

## TL;DR

This study identifies key genes linked to reduced fertility in older male mice, offering insights into age-related male infertility.

## Contribution

The study identifies nine hub genes and altered pathways associated with decreased fertility in older male mice.

## Key findings

- Spermatogonia and sperm counts were significantly lower in 12-month-old mice.
- 449 differentially expressed genes were identified, with nine hub genes and mitochondrial-related DEGs.
- Altered pathways were enriched in Gene Ontology and KEGG analyses.

## Abstract

Aging and delayed parenthood are major social concerns. Men older than 35 years, which is an advanced paternal age, experience reduced sperm quality and fertility.

In this study, 12-month-old mice served as a model for males of advanced paternal age. RNA sequencing (RNA-seq) of epididymides from 2- and 12-month-old mice was performed.

Spermatogonia and sperm counts were significantly lower in these mice. We identified 449 differentially expressed genes by RNA-seq. Altered pathways were enriched using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, nine hub genes were identified from the DEGs, along with DEGs associated with mitochondria.

These results could enhance understanding of the molecular mechanisms underlying decreased male fertility in men of advanced paternal age and may aid in developing targeted treatment for male infertility related to aging.

## Linked entities

- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** male infertility (MESH:D007248)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12006134/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12006134/full.md

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Source: https://tomesphere.com/paper/PMC12006134