Testosterone deficiency was reported together with signs of atherosclerosis in epidemiological studies, however, there is currently no evidence for a causal relationship 12, 13, 14. A more recent study demonstrated that testicular vasculature might also be important for germ cell defects found in Klinefelter syndrome 11. Reduction of blood flow due to decreased diameter of microvascular lumen in testes was suggested as a possible cause for degenerative changes of germ cells, oligospermia in humans 8 and age-dependent disturbances of spermatogenesis 9, 10. In man, early investigations of undescended testes linked reduced blood perfusion to atrophy and hypoplasia of the organ 7. The appearance of a regular testicular microvasculature was described previously for different species 3, 4, 5, 6. Focal tubular sclerosis was also reported in association with atherosclerotic lesions of interstitial testicular vessels 2.ДЇor a given organ, a healthy capillary vascular bed with its regular architecture is the prerequisite for adequate perfusion and function of this organ. Thus, this study calls for specific treatment of male infertility induced by microvascular damage through hypercholesterolemia and atherosclerosis.Дecline of androgen blood levels, dysfunctional sperm, and histologic changes, such as focal atrophy of seminiferous tubules and reduction of tubular diameter, are considered signs of male hypogonadism 1. Our data suggest reduced testosterone levels in this atherosclerosis model might be explained by both, rarefication of the capillary network and reduced Leydig cell number and size.

Reduced litter size of the KO mice suggests hypo- or infertility as a consequence of the testicular defects. These structural changes in the testis occurred on an inflammatory background revealed by qPCR. Stereological analyses of interstitial cells demonstrated significantly reduced Leydig cell numbers and size. In addition to micro-CT investigations for bigger vessels, stereology revealed a reduction of capillary length, volume and surface area suggesting capillary rarefaction as a factor for diminished testosterone.

In KO mice, overall testosterone levels were reduced whereas the adrenal gland-specific corticosterone was increased excluding a general defect of steroid hormone production. We used the apolipoprotein E (ApoE)/low density lipoprotein (LDL) receptor deficient mouse model (KO) for atherosclerosis (20, 40, 60 and 87-week-old) to investigate whether Leydig cells or the capillary network are responsible for reduced serum testosterone levels previously observed in extreme ages of this model. Visiopharm hopes to introduce the technology in 2008.The testis as a site for atherosclerotic changes has so far attracted little attention. In combination with our automated physical dissector and our ability to interface with commercially available virtual microscopes, the Proportionator will propel unbiased methods into the realm of high-throughput analysis.вЂќ Visiopharm CSO Niels Foged said, вЂњWe and the inventors believe this method will revolutionise modern stereology, and we are excited about implementing it on our histoinformatics platform. The researchers claim an increase in precision and reduction in work load as a result, and have demonstrated efficiency increases as high as 30 times above the traditional sampling methods.

While the Proportionator is a strictly unbiased method, in contrast to the established systematic uniform random sampling procedures, it is based on a non-uniform sampling. Quantitative microscopy specialist Visiopharm AB of Horsholm, has signed a licence agreement with the Stereology and Electron Microscopy Research Laboratory at Aarhus University, Denmark for the further development of Proportionator, a stereological sampling technique developed and patented by Jonathan Gardi, together with Hans JГёrgen Gundersen and Jens Nyengaard.

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