Mixed testicular atrophy related to atherosclerosis: first lessons from the ApoE-/-/LDL receptor-/- double knockout mouse model

被引：8
|
作者：
Langheinrich, A. C. [2 ]
Paradowska, A. [1 ]
Kilinski, R. [2 ]
Kampschulte, M. [2 ]
Steinfeld, K. [1 ]
Altinkilic, B. [1 ]
Steger, K. [1 ]
Stieger, P. [3 ]
Bergmann, M. [4 ]
Weidner, W. [1 ]
机构：
[1] Univ Giessen, Dept Urol Pediat Urol & Androl, D-35392 Giessen, Germany
[2] Univ Giessen, Dept Radiol, D-35392 Giessen, Germany
[3] Univ Giessen, Dept Cardiol, D-35392 Giessen, Germany
[4] Univ Giessen, Dept Vet Anat Histol & Embryol, D-35392 Giessen, Germany
来源：
INTERNATIONAL JOURNAL OF ANDROLOGY | 2012年 / 35卷 / 04期
关键词：
ApoE-; -; LDL receptor-; - double knockout mouse model; atherosclerosis; micro-CT; mixed testicular atrophy; VASA VASORUM NEOVASCULARIZATION; DENSITY-LIPOPROTEIN RECEPTOR; APOLIPOPROTEIN-E; SEMINIFEROUS TUBULES; MICE LACKING; HYPOXIA; MEN; SPERMATOGENESIS; TESTIS; SPERMATOGONIA;
D O I：
10.1111/j.1365-2605.2011.01228.x
中图分类号：
R69 [泌尿科学（泌尿生殖系疾病）];
学科分类号：
摘要：
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 mu m(3)) voxel size. Testes (n = 8) of C57/BL mice at the same age served as controls. Testis volume (mm(3)) and total vascular volume fraction (mm(3)) 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.
引用
收藏
页码：562 / 571
页数：10
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