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High cholesterol diet–induced testicular dysfunction in rats

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Abstract

Purpose

Hypercholesterolemia due to a high-cholesterol diet is linked to numerous diseases and may lead to male infertility. However, the underlying mechanism remains unknown. The maintenance of male fertility requires intact testicular structures (including seminiferous tubules and mesenchyme) and functioning cells (Leydig cells, Sertoli cells and germ cells, etc.), production of appropriate concentrations of sex hormones, and cooperation among testicular cells. Thus, we considered whether male fertility declined as the structure and function of testicular cells were altered in rats on a high-cholesterol diet.

Methods

Male Sprague Dawley rats were fed either a standard or a high-cholesterol diet for 16 weeks. Serum sex hormones, lipid components, semen quality, and fertility rate were assayed in the rats. The 3β-hydroxysteroid dehydrogenase (3β-HSD), Wilms tumor 1 (WT-1), and deleted in azoospermia-like (DAZL) were regarded as specific markers of Leydig, Sertoli, and germ cells in rats. In addition, the ultrastructure of the testis and expression levels of particular marker molecules of testicular cells were further investigated.

Results

Compared to rats fed on a regular diet, the serum testosterone levels and sperm progressive motility decreased in rats fed high cholesterol. Moreover, we observed a deformed nucleus, dilated smooth endoplasmic reticulum, and swollen mitochondria of Leydig cells and a schizolytic nucleus of Sertoli cells in rats on a high-cholesterol diet. The 3β-HSD, WT-1, and DAZL protein expression levels were significantly reduced in rats on a high-cholesterol diet.

Conclusions

Our results showed that a high-cholesterol diet adversely affected testosterone production and sperm progressive motility, possibly due to Leydig, Sertoli, and germ cell abnormalities.

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Data Availability

The datasets generated and analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Abbreviations

StAR:

steroidogenic acute regulatory protein

3β-HSD:

3β-hydroxysteroid dehydrogenase

WT-1:

Wilms tumor gene

DAZL:

deleted in azoospermia-like

ND:

normal diet

HC:

high-cholesterol diet

SSA:

surplus semen analysis

PR:

progressive motility

NP:

non-progressive motility

IM:

immobility

TG:

triacylglycerol

TC:

total cholesterol

LDL-C:

low-density lipoprotein cholesterol

HDL-C:

high-density lipoprotein cholesterol

LH:

luteinizing hormone

FSH:

follicle stimulating hormone

ELISA:

enzyme-linked immunosorbent assay

TBST:

Tris-buffered saline containing 0.1% Tween 20

SEM:

standard error of mean

HPG:

hypothalamic–pituitary–gonadal

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Funding

This work was supported by the National Natural Science Foundation of China (82270839 and 81770860) and Key Research and Development Plan of Shandong Province (2017CXGC1214).

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Authors and Affiliations

  1. Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Jinan, 250021, Shandong, China

    Luna Liu, Fangjie Jiang, Dandan Luo, Shuang Liu, Yu Su, Qingbo Guan & Chunxiao Yu

  2. Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Institute of Endocrine and Metabolic disease, Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, 250021, Shandong, China

    Luna Liu, Dandan Luo, Shuang Liu, Yu Su, Qingbo Guan & Chunxiao Yu

  3. Jing’an District Center Hospital, Fudan University, Shanghai, 200433, China

    Meijie Zhang

  4. Department of Rehabilitation, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People’s Republic of China

    Fangjie Jiang

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  1. Luna Liu
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Contributions

Luna Liu was involved in the writing of the manuscript, performed part of the experiments, and contributed to the revision of the manuscript. Meijie Zhang and Fangjie Jiang conducted part of the experiments. Dandan Luo, Shuang Liu, Yu Su, and Qingbo Guan contributed to feeding the rats and analyzing the data. Chunxiao Yu designed the study and directed the project. All authors read and approved the final manuscript.

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Correspondence to Chunxiao Yu.

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All animal protocols and procedures were approved by the Animal Ethics Committee of Shandong Provincial Hospital and performed according to the Shandong Provincial Hospital Animal Care and Use Committee.

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Liu, L., Zhang, M., Jiang, F. et al. High cholesterol diet–induced testicular dysfunction in rats. Hormones 22, 685–694 (2023). https://doi.org/10.1007/s42000-023-00472-4

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