期刊
INTERNATIONAL JOURNAL OF ANDROLOGY
卷 35, 期 4, 页码 562-571出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2605.2011.01228.x
关键词
ApoE-; -; LDL receptor-; - double knockout mouse model; atherosclerosis; micro-CT; mixed testicular atrophy
类别
资金
- DFG KFO [181/2, 8 (WE 2324/3-1)]
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.
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