Depression-related testosterone deficiency is linked to reduced cholesterol levels in Leydig cells of CUMS mice

in Reproduction
Authors:
Jiaojiao Huang College of Life Science, Qingdao Agricultural University, Qingdao, China

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https://orcid.org/0000-0002-4421-2967
,
Xinyu Li College of Life Science, Qingdao Agricultural University, Qingdao, China

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Dongyu Zhang College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China

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Luzhen Wang College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China

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Zhao Li Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao, China

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Zhenhua Song Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao, China

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Correspondence should be addressed to Z Song: songzh@qdu.edu.cn
DOI:
https://doi.org/10.1530/REP-24-0081
Volume/Issue:
Volume 168: Issue 4
Article ID:
e240081
Article Type:
Research Article
Online Publication Date:
05 Sep 2024
Copyright:
© the author(s) 2024
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In brief

Male reproductive problems under psychological stress were widely studied. Using chronically unpredictable mild stress-treated mice, we found that reduced serum testosterone levels were related to the low level of cholesterol in the Leydig cells.

Abstract

Testosterone deficiency in humans can be caused by depressive symptoms; however, the causes of this deficiency are incompletely understood. This study demonstrates that male mice with depression-like symptoms due to chronic unpredictable mild stress (CUMS) show reduced serum testosterone levels and disrupted sexual behaviors. However, the observed testosterone reductions were not caused by apoptosis of Leydig cells. Oil red O staining revealed that lipid droplets were dramatically decreased in Leydig cells, suggesting that defects in cholesterol uptake might be related to testosterone deficiency in depression-like mice. To investigate the potential mechanism, lipid homeostasis was examined by liquid chromatography-tandem mass spectrometry. The results revealed that higher levels of sphingomyelins (SM 8:0;2O/28:1, 18:0;2O/22:2, 33:0;3O, 33:1;2O) were linked to decreased cholesterol levels. Further investigation indicated that testosterone biosynthesis from cholesterol in Leydig cells was impaired by the downregulation of Ldlr, Srb1, Lhr, and P450scc. Elevated levels of interferon signaling-associated pathways in depression-like mice testes may also contribute to decreased testosterone levels. Taken together, these findings provide a novel understanding of male reproductive problems under psychological stress and suggest that cholesterol uptake might be a causal factor in reduced testosterone production in depression-like mice.

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

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