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Cited by 17Sperm and Testicular FunctionHormonal and reproductive studiesAtherosclerosis and Cardiovascular Diseases

Low testosterone in ApoE/LDL receptor double-knockout mice is associated with rarefied testicular capillaries together with fewer and smaller Leydig cells

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Steinfeld, Kai, Beyer, Daniela, Mühlfeld, Christian, Mietens, Andrea, Eichner, Gerrit, Altinkilic, Bora, Kampschulte, Marian, Jiang, Qingkui +4 more·2018·Scientific Reports
DOI 10.1038/s41598-018-23631-9PMC PMC5882941
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Abstract

The testis as a site for atherosclerotic changes has so far attracted little attention. We used the apolipoprotein E (ApoE)/low density lipoprotein (LDL) receptor deficient mouse model (KO) for atherosclerosis (20, 40, 60 and 87-week-old) to investigate whether Leydig cells or the capillary network are responsible for reduced serum testosterone levels previously observed in extreme ages of this model. In KO mice, overall testosterone levels were reduced whereas the adrenal gland-specific corticosterone was increased excluding a general defect of steroid hormone production. In addition to micro-CT investigations for bigger vessels, stereology revealed a reduction of capillary length, volume and surface area suggesting capillary rarefaction as a factor for diminished testosterone. Stereological analyses of interstitial cells demonstrated significantly reduced Leydig cell numbers and size. These structural changes in the testis occurred on an inflammatory background revealed by qPCR. Reduced litter size of the KO mice suggests hypo- or infertility as a consequence of the testicular defects. Our data suggest reduced testosterone levels in this atherosclerosis model might be explained by both, rarefication of the capillary network and reduced Leydig cell number and size. Thus, this study calls for specific treatment of male infertility induced by microvascular damage through hypercholesterolemia and atherosclerosis.

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  • ApoE/LDL receptor-deficient mice exhibit testicular microvascular damage and reduced serum testosterone, leading to infertility.

    “These deficient mice exhibited testicular microvascular damage and reduced serum testosterone levels, ultimately leading to mice infertility.17”

    From The First Case of Lipoprotein Glomerulopathy in a Patient With Male Infertility (2026) · cites this paper as [17]

    The Discussion reports testicular capillary rarefaction and reduced serum testosterone in ApoE/LDL receptor double-knockout mice. The Abstract says reduced litter size suggests hypo- or infertility as a consequence of testicular defects, but the claim states infertility as a definite outcome. The Discussion also says female fertility disturbances cannot be excluded as a contributor to reduced litter size. (LLM, conf=0.88)

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Authors
Steinfeld, K., Beyer, D., Mühlfeld, C., Mietens, A., Eichner, G., Altinkilic, B., Kampschulte, M., Jiang, Q., Krombach, G. A., Linn, T., Weidner, W., & Middendorff, R.
Affiliations
  • Justus-Liebig-Universität Gießen (DE)
  • Medizinische Hochschule Hannover (DE)
Corresponding author
  • Weidner, Wolfgang
  • Middendorff, Ralf
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-04-03
Volume
8
Issue
1
Pages
5424-5424
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-23631-9
PMC
PMC5882941
OpenAlex
W2806932183
Cited by
17
References
0
Citations by year
2026: 3 · 2025: 2 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 1
FWCI
1.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • University writing server of the Justus Liebig University Giessen (Justus-Liebig-Universität Gießen) (submittedVersion, cc-by)
  • Universitätsbibliothek Gießen (cc-by)
Funders
Deutsche Forschungsgemeinschaft (KFO 181)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
androgen deficiency, Leydig cells, capillary rarefaction, atherosclerosis, hypercholesterolemia, male infertility, corticosterone, litter size, testicular inflammation
MeSH terms
Animals, Apolipoproteins E, Body Weight, Capillaries, Cell Count, Leydig Cells, Male, Organ Size, Receptors, LDL, Testosterone, Cell Size, Mice, Gene Knockout Techniques

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