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  2. Diet-induced obesity is associated with altered expression of sperm motility-related genes and testicular post-translational modifications in a mouse model

Diet-induced obesity is associated with altered expression of sperm motility-related genes and testicular post-translational modifications in a mouse model

  • Theriogenology. 2020 Dec;158:233-238. doi: 10.1016/j.theriogenology.2020.09.023.
Fang Wang 1 Houyang Chen 2 Ying Chen 3 Yimin Cheng 1 Jia Li 4 Liping Zheng 4 Xuhui Zeng 5 Tao Luo 6
Affiliations

Affiliations

  • 1 Institute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, 330031, China.
  • 2 Reproductive Medical Center, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, China.
  • 3 Institute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, 330031, China; Key Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Jiangxi Medical College of Nanchang University, Nanchang University, Nanchang, Jiangxi, 330031, China.
  • 4 Key Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Jiangxi Medical College of Nanchang University, Nanchang University, Nanchang, Jiangxi, 330031, China.
  • 5 Institute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, 330031, China; Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, 226000, PR China.
  • 6 Institute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi, 330031, China; Key Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Jiangxi Medical College of Nanchang University, Nanchang University, Nanchang, Jiangxi, 330031, China. Electronic address: luotao@ncu.edu.cn.
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.

Keywords

Gene expression; Histone modifications; Male obesity; Male reproductive functions; Post-translational modifications.

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