Diet-induced obesity is associated with altered expression of sperm motility-related genes and testicular
Fang Wang1, Houyang Chen2, Ying Chen3
1Institute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, 330031, China.
Abstract:
Obesity is a metabolic disease and its relation with male subfertility has aroused a growing concern. However, it is unclear whether gene expression and post-translational modifications (PTMs), two vital molecular mechanisms regulating cellular functions, are associated with obesity-induced male reproductive dysfunction. In this study, male obesity with compromised sperm motility was induced by a high-fat diet (HFD) using a mouse model. The expression of motility related-genes, the level of histone modifications, and the global profiles of post-translational modifications (PTMs), were examined in testes of HFD and control mice by quantitative real-time PCR and western blot, respectively. Outer dense fiber protein 2, a major component of outer dense fibers in the sperm tail, is the most obviously down-regulated gene out of 11 evaluated genes, showing a reduction of about 50% RNA level in testes of obese male mice compared with that in control mice. Semi-quantitative analysis of the western blot demonstrated that ∼56% enrichment of di-methylated histone (H)3 lysine (K)36, ∼59% enrichment of 2-hydroxyisobutyrylated H4K8, ∼32% decrease of propionylated H3K23, ∼33% decrease of crotonylated H4K8, and ∼45% decrease of acetylated H3K122 and H4K8 were detected in testes of male HFD mice compared with that in control mice. In addition, male obesity up-regulated the testicular levels of ubiquitination by ∼18%, tyrosine nitration by ∼20%, lysine succinylation by ∼25%, lysine benzoylation by ∼28%, lysine malonylation by ∼32%, lysine glutarylation by ∼36%, lysine propionylation by ∼42%, lysine 2-hydroxyisobutyrylation by ∼45%, and SUMO1 modification by ∼59%, and down-regulated the testicular levels of O-GlcNAcylation by ∼12%, lysine crotonylation by ∼22%, and lysine acetylation by 35%. These findings indicate that altered gene expression and PTMs are associated with the obesity-induced male reproductive dysfunction.
Insights
Obesity impairs male fertility by altering gene expression and post-translational modifications (PTMs) in the testes. A high-fat diet in mice reduced sperm motility and changed key protein modifications, impacting male reproductive health.
Area of Science:
- Reproductive Biology
- Metabolic Disease Research
- Molecular Endocrinology
Background:
- Obesity is a growing concern linked to male subfertility.
- The molecular mechanisms, including gene expression and post-translational modifications (PTMs), underlying obesity-induced male reproductive dysfunction are not fully understood.
Purpose of the Study:
- To investigate the association between obesity, altered gene expression, and PTMs in the context of male reproductive dysfunction.
- To examine changes in motility-related genes and histone/global PTMs in the testes of male mice fed a high-fat diet.
Main Methods:
- A high-fat diet (HFD) was used to induce obesity and male subfertility in a mouse model.
- Quantitative real-time PCR was employed to assess the expression of 11 motility-related genes.
- Western blot analysis was performed to examine global PTM profiles and specific histone modifications in testicular tissue.
Main Results:
- HFD significantly down-regulated the expression of Outer dense fiber protein 2, a key sperm tail component.
- Obesity altered numerous testicular PTMs, including significant changes in histone modifications (e.g., H3K36 di-methylation, H4K8 2-hydroxyisobutyrylation) and global PTMs (e.g., increased ubiquitination, SUMO1 modification; decreased O-GlcNAcylation, lysine acetylation).
Conclusions:
- Altered gene expression and a wide range of dysregulated post-translational modifications in the testes are associated with obesity-induced male reproductive dysfunction.
- These molecular changes highlight potential pathways contributing to subfertility in obese males.
