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Updated: May 26, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Mixed testicular atrophy related to atherosclerosis: first lessons from the ApoE(-/-)/ LDL receptor(-/-) double
A C Langheinrich1, A Paradowska, R Kilinski
1Department of Radiology, Justus Liebig University of Giessen, Giessen, Germany.
Abstract:
Age-related testicular changes are associated with declining spermatogenesis and testosterone levels. A relationship to atherosclerosis has never been investigated systematically. The ApoE(-/-)/LDL receptor(-/-) double knockout mouse model, providing a remarkable homology to human atherosclerosis, is an ideal tool to investigate spermatogenetic alterations in this context. Testes (n = 10) from ApoE(-/-)/LDL receptor(-/-) double knockout mice at the age of 80 weeks were perfused in vivo with contrast agent, harvested and scanned with micro-CT at (4.9 μm³) voxel size. Testes (n = 8) of C57/BL mice at the same age served as controls. Testis volume (mm³) and total vascular volume fraction (mm³) were quantified using micro-CT. Serum testosterone levels were determined. Testicular histology and epididymal sections were analysed for tubular structure, spermatogenetic scores and sperm count. The expression of protamine 2 as a marker for elongated spermatids, inflammation markers (CD4, F4/80) and hypoxia inducible factor 1 alpha (HIF1 alpha) were investigated using immunohistochemistry. ApoE(-/-)/LDL receptor(-/-) double knockout mice exhibit diminished testis and vascular volume fraction with respect to that of controls (p < 0.001). These findings were associated with a reduction of testosterone levels (p < 0.001). Mixed atrophy was present in 41% of the seminiferous tubuli in ApoE(-/-)/LDL receptor(-/-) double knockout mice at the age of 80 weeks. Sperm counts from the epididymis demonstrated a significant decrease in ApoE(-/-)/LDL receptor(-/-) double knockout mice (p < 0.001). In addition, sperm specific protamine 2 expression was decreased in testicular tissue and epididymis of ApoE(-/-)/LDL receptor(-/-) double knockout mice compared with that of control mice. Peritubular inflammatory infiltration and the expression of the hypoxia related marker was observed. Mixed testicular atrophy in ApoE(-/-)/LDL receptor(-/-) double knockout mice is linked to reduced testis volume, vascular volume fraction and low testosterone serum levels, suggesting a direct relation between atherosclerosis and disturbed spermatogenesis.
Insights
Atherosclerosis in mice significantly reduces testicular volume, vascularity, and testosterone, leading to impaired spermatogenesis and sperm counts. This study links cardiovascular disease to reproductive health decline.
Area of Science:
- Reproductive biology and endocrinology
- Cardiovascular research
- Atherosclerosis modeling
Background:
- Age-related testicular changes include decreased spermatogenesis and testosterone.
- The link between atherosclerosis and testicular function has not been systematically studied.
- ApoE(-/-)/LDL receptor(-/-) double knockout mice mimic human atherosclerosis.
Purpose of the Study:
- To investigate the impact of atherosclerosis on testicular structure and function.
- To evaluate spermatogenesis, testosterone levels, and testicular vascularity in a mouse model of atherosclerosis.
Main Methods:
- Utilized ApoE(-/-)/LDL receptor(-/-) double knockout mice and C57/BL controls (80 weeks old).
- Employed micro-CT scanning for testicular and vascular volume quantification.
- Assessed serum testosterone, testicular histology, sperm counts, and molecular markers (protamine 2, inflammation, hypoxia).
Main Results:
- Atherosclerotic mice showed significantly reduced testis volume and vascular volume fraction.
- Testosterone levels were markedly lower in knockout mice, associated with mixed testicular atrophy.
- Sperm counts and protamine 2 expression were decreased; inflammation and hypoxia markers were elevated.
Conclusions:
- Atherosclerosis in ApoE(-/-)/LDL receptor(-/-) mice is directly associated with testicular atrophy.
- Reduced testicular vascularity and low testosterone levels contribute to disturbed spermatogenesis.
- Findings suggest a significant link between atherosclerosis and impaired male reproductive health.
