Obesity induces male mice infertility via oxidative stress, apoptosis, and glycolysis

in Reproduction
Authors:
Jianqiu HanCollege of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai, China

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Chen ZhaoMolecular Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany

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Huixia GuoCollege of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai, China

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Tengfei LiuShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

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Yongmei LiShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

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Yalei QiShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

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Jan M DeussingMolecular Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany

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Yanjia ZhangShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

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Juan TanShanghai Key Laboratory of Brain Functional Genomics, Ministry of Education of Life Sciences, East China Normal University, Shanghai, China

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Honghui HanShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

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Xueyun MaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

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https://orcid.org/0000-0002-6207-5740
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Correspondence should be addressed to X Ma or H Han or J Tan; Email: xyma@bio.ecnu.edu.cn or hhhan@bio.ecnu.edu.cn or jtan@brain.ecnu.edu.cn

*(J Han and C Zhao contributed equally to this work)

DOI:
https://doi.org/10.1530/REP-23-0097
Volume/Issue:
Volume 166: Issue 1
Page Range:
27–36
Article Type:
Research Article
Online Publication Date:
26 May 2023
Copyright:
© Society for Reproduction and Fertility 2023
Restricted access

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In brief

The current declining trend in male fertility parallels the increasing prevalence of obesity worldwide. This paper revealed that the poor in vitro fertilization rates and decreased sperm motility in obese mice due to excessive oxidative stress enhanced apoptosis and impaired glucose metabolism in the testes.

Abstract

Obesity is an urgent public health problem in recent decades, linked to reduced reproductive potential, and negatively affects the success of assisted reproduction technology. The aim of this study is to investigate the mechanisms underlying impaired male fertility caused by obesity. Male C57BL/6 mice fed a high-fat diet for 20 weeks served as mouse models with moderate (20% < body fat rate (BFR) < 30%) and severe obesity (BFR > 30%). Our results showed poor in vitro fertilization rates and decreased sperm motility in obese mice. Abnormal testicular structures were identified in male mice with moderate and severe obesity. The expression level of malondialdehyde increased with obesity severity. This finding indicates that oxidative stress plays a role in male infertility caused by obesity, which was further confirmed by the decreased expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase, and glutathione peroxidases. Our study also found that the expression of cleaved caspase-3 and B-cell lymphoma-2 showed an obesity severity-dependent manner indicating that apoptosis is highly correlated with male infertility caused by obesity. Moreover, the expression of glycolysis-related proteins, including glucose transporter 8, lactate dehydrogenase A, monocarboxylate transporter 2 (MCT2), and MCT4, decreased significantly in the testes of obese male mice, suggesting energy supply for spermatogenesis is impaired by obesity. Taken together, our findings provide evidence that obesity impairs male fertility through oxidative stress, apoptosis, and blockage of energy supply in the testes and suggest that male obesity influences fertility through complex and multiple mechanisms.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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