Testis Atrophy and Hypogonadism in ApoE-/-/LDL-/- double knockout Mice

Ziele: Aging and atherogenesis are seemingly inseparably linked. Age related decline of testosterone levels is referred to as andropause, hypogonadism and declining testicular function, but its relation to atherosclerosis is not yet defined. Therefore, we investigated testicular morphology in apoE-/-/LDL-/- double knockout mice. Methode: Testes from apoE-/-/LDL-/- double knockout mice at the age of 80 weeks (n=8) were in-vivo perfused with contrast agent, harvested and scanned with micro-CT at (4.9µm)3 voxel size. Testes of C57/BL mice at the age of 72 weeks served as controls (n=10). Testis volume (mm3) and total vascular volume fraction (mm3) were quantified using micro-CT. Free serum testosterone and gonadotropin levels were determined in all mice. Results were complemented with co-localized histology. Ergebnis: Mixed atrophy was present in 41% of the seminiferous tubuli in apoE-/-/LDL-/- double knockout mice at the age of 80 weeks. These findings were associated with a significant reduction of the total testis and vascular volume fraction compared to controls (p<0.001). Quantitative analyses of sperm counts from the cauda epididymidis demonstrated a significant decrease in apoE-/-/LDL-/- double knockout mice at the age of 80 weeks (p<0.001) compared to wild-type mice. Infiltration of immuncompetent cells was observed in the testes interstitium of apoE-LDL double knockout mice. Double knockout mice showed significantly lower free testosterone levels as compared to controls (p<0.001). Schlussfolgerung: Mixed atrophy in apoE-/-/LDL-/- double knockout mice is linked to testis volume, vascular volume fraction and hypotestosteronemia, suggesting a direct relation of ageing, atherosclerosis and spermatogenesis.