{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:13:54Z","timestamp":1791346434178,"version":"4.3.1"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,12,13]],"date-time":"2011-12-13T00:00:00Z","timestamp":1323734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J of Andrology"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Age\u2010related testicular changes are associated with declining spermatogenesis and testosterone levels. A relationship to atherosclerosis has never been investigated systematically. The ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>\/LDL receptor<jats:sup>\u2212\/\u2212<\/jats:sup> double knockout mouse model, providing a remarkable homology to human atherosclerosis, is an ideal tool to investigate spermatogenetic alterations in this context. Testes (<jats:italic>n\u2003<\/jats:italic>=\u200310) from ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>\/LDL receptor<jats:sup>\u2212\/\u2212<\/jats:sup> double knockout mice at the age of 80\u2003weeks were perfused <jats:italic>in vivo<\/jats:italic> with contrast agent, harvested and scanned with micro\u2010CT at (4.9\u2003\u03bcm\u00b3) voxel size. Testes (<jats:italic>n\u2003<\/jats:italic>=\u20038) of C57\/BL mice at the same age served as controls. Testis volume (mm\u00b3) and total vascular volume fraction (mm\u00b3) were quantified using micro\u2010CT. 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<jats:sup>\u2212\/\u2212<\/jats:sup>\/LDL receptor<jats:sup>\u2212\/\u2212<\/jats:sup> double knockout mice exhibit diminished testis and vascular volume fraction with respect to that of controls (<jats:italic>p\u2003<\/jats:italic>&lt;\u20030.001). These findings were associated with a reduction of testosterone levels (<jats:italic>p\u2003<\/jats:italic>&lt;\u20030.001). Mixed atrophy was present in 41% of the seminiferous tubuli in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>\/LDL receptor<jats:sup>\u2212\/\u2212<\/jats:sup> double knockout mice at the age of 80\u2003weeks. Sperm counts from the epididymis demonstrated a significant decrease in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>\/LDL receptor<jats:sup>\u2212\/\u2212<\/jats:sup> double knockout mice (<jats:italic>p\u2003<\/jats:italic>&lt;\u20030.001). In addition, sperm specific protamine 2 expression was decreased in testicular tissue and epididymis of ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>\/LDL receptor<jats:sup>\u2212\/\u2212<\/jats:sup> 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<jats:sup>\u2212\/\u2212<\/jats:sup>\/LDL receptor<jats:sup>\u2212\/\u2212<\/jats:sup> 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.<\/jats:p>","DOI":"10.1111\/j.1365-2605.2011.01228.x","type":"journal-article","created":{"date-parts":[[2011,12,13]],"date-time":"2011-12-13T07:45:40Z","timestamp":1323762340000},"page":"562-571","source":"Crossref","is-referenced-by-count":15,"title":["Mixed testicular atrophy related to atherosclerosis: first lessons from the ApoE<sup>\u2212\/\u2212<\/sup>\/\u200aLDL receptor<sup>\u2212\/\u2212<\/sup> double knockout mouse model"],"prefix":"10.1111","volume":"35","author":[{"given":"A. 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