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P8 Atherosclerosis-related disturbances of spermatogenesis: lessons from the ApoE-/-/LDL receptor-/- knockout mouse model and prospective investigations in men

Generally, age-related testicular changes are associated with an increase of germ cell degeneration, decline of spermatogenesis and androgen decline resulting in a gradual decrease of sperm count. Unfortunately, an association of these findings to vascular atherosclerotic alterations has never been investigated systematically, although arterial lesions in testicular biopsies of azoospermic men have been described already 30 years ago.

In developed countries the wish for fathership in ageing is increasing. Furthermore, there is an increasing prevalence of young men who suffer from lipid metabolic disorders which cause precocious atherosclerotic lesions in different organ systems affecting cardiac and renal terminal vessels. Unfortunately, there is a lack of knowledge concerning similar lesions in testicular microvasculature. The mutant ApoE-/-/LDL receptor-/- double knockout mouse model provides a considerable homology to human atherosclerosis with an additional reduction of the total testicular and total vascular volume, evidence of testicular mixed atrophy, decreased number of sperms in the cauda epididymidis and serum testosterone deficiency. We consider the ApoE-/-/LDL receptor-/- double knockout mouse model as an ideal tool to investigate unexplained infertility with its special relationship to germ cell defects in association of local vascular lesions. The experimental investigations are completed by prospective clinical investigations resulting in vasculature-related analyses of biopsy material from nonobstructive azoospermic men with and without atherosclerotic findings.