Atherosclerosis-related disturbances of spermatogenesis: lessons from the ApoE'^VLDL receptor'^' knockout mouse model and prospective investigations in men

动脉粥样硬化相关的精子发生障碍：ApoE^VLDL 受体^ 敲除小鼠模型的教训和男性前瞻性研究

• 批准号: 202291505
• 负责人: Professor Dr. Thomas Linn
• 金额: --
• 依托单位: Institut für Anatomie und Zellbiologie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/202291505?language=en
• 关键词: Atherosclerosis; related; disturbances; spermatogenesis; lessons

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 fathershlp 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'^VLDL 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 epidldymldls and serum testosterone deficiency. We consider the ApoE"'7LDL 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.

通常，与年龄相关的睾丸变化与生殖细胞变性增加、精子发生下降和雄激素下降相关，导致精子计数逐渐减少。不幸的是，这些发现与血管动脉粥样硬化改变的关联从未被系统地研究过，尽管30年前已经描述了无精子症男性睾丸活检中的动脉病变。在发达国家，老年人希望得到父亲的帮助的愿望正在增加。此外，患有脂质代谢紊乱的年轻男性的患病率越来越高，脂质代谢紊乱导致影响心脏和肾脏终末血管的不同器官系统中的过早动脉粥样硬化病变。遗憾的是，目前对睾丸微血管的类似病变缺乏了解。突变型ApoE + VLDL受体+双敲除小鼠模型提供了与人动脉粥样硬化相当大的同源性，同时总睾丸和总血管体积额外减少，睾丸混合萎缩的证据，尾状核中精子数量减少和血清睾酮缺乏。我们认为ApoE“7LDL受体”“双敲除小鼠模型是研究原因不明不孕症的理想工具，其与生殖细胞缺陷的特殊关系与局部血管病变有关。通过前瞻性临床研究完成实验研究，对有和无动脉粥样硬化结果的非阻塞性无精子症男性的活检材料进行血管相关分析。