Journal article

Publication year: 2012

Pages: 562-571

Journal: International Journal of Andrology

Volume number: 35

Issue number: 4

ISSN: 0105-6263

Open access status: Bronze

DOI Link: https://doi.org/10.1111/j.1365-2605.2011.01228.x

Publisher: Wiley

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 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.

Harvard Citation style: Langheinrich, A., Paradowska, A., Kilinski, R., Kampschulte, M., Steinfeld, K., Altinkilic, B., et al. (2012) Mixed testicular atrophy related to atherosclerosis: first lessons from the ApoE^-/-/LDL receptor^-/- double knockout mouse model, International Journal of Andrology, 35(4), pp. 562-571. https://doi.org/10.1111/j.1365-2605.2011.01228.x

APA Citation style: Langheinrich, A., Paradowska, A., Kilinski, R., Kampschulte, M., Steinfeld, K., Altinkilic, B., Steger, K., Stieger, P., Bergmann, M., & Weidner, W. (2012). Mixed testicular atrophy related to atherosclerosis: first lessons from the ApoE^-/-/LDL receptor^-/- double knockout mouse model. International Journal of Andrology. 35(4), 562-571. https://doi.org/10.1111/j.1365-2605.2011.01228.x