肥胖男性生殖功能低下的线粒体损伤机制研究

Obesity is an important problem of public health. Not only obesity can increase the risks of diabetes and cardiovascular and cerebrovascular diseases, but also has close correlativity with the hot present global action: male reproductive function reduction which has been becoming a new hot spot in obesity investigation. Nowadays, the trends of researches are focus on sperm lesion and testosterone hormone level reduction which are related to obese lipid metabolism disorder and oxidative damage, however, there haven't the mechanism research of mitochondrial damage about obesity leads to reduce male reproductive function until now. There are numerous mitochondria in testicular germ cells and interstitial cells, which are sensitive to energy, and if mitochondria are damaged, the quality and function of testicular germ cells will be reduced for lack of energy supply and the testosterone hormone level will be reduced for lack of energy supply too. Our preliminary study found that diet-induced obesity rats existed testicle mitochondrial oxidative damage, and then we made a scientific hypothesis as the mechanism of male reproductive function reduction by obesity is testicle mitochondrial oxidative damage. This project analyses the relation between obese male reproductive function reduction and mitochondrial oxidative damage through the population test; explores the mechanism of mitochondrial dysfunction in diet-induced obesity rats, and researches the alimentary protective factors of mitochondrial dysfunction, which can supply new ideas for obese male reproductive function studies and provide scientific basis of increasing obese male reproductive function from dietary orientation.

肥胖是重要的公共卫生问题，肥胖不仅增加糖尿病、心脑血管疾病等的发病风险，而且与目前全球重点关注的男性生殖功能降低也密切相关，这成为肥胖领域的一个新热点。目前肥胖生殖研究集中在精子损伤和睾酮激素水平降低两方面，并且与肥胖的脂代谢紊乱和氧化损伤有关，但是，未见肥胖导致男性生殖功能低下的线粒体损伤机制研究。睾丸生殖细胞（包括间质细胞）的线粒体数量多，对能量变化敏感，如果线粒体损伤，睾丸生殖细胞的质量和功能因供能不足而降低。我们前期研究发现肥胖大鼠存在睾丸线粒体氧化损伤，于是提出"肥胖导致男性生殖功能低下的机制是睾丸线粒体氧化损伤"的科学假设。本项目通过人群试验分析肥胖男性生殖功能低下与线粒体损伤的关系；动物实验动态观察肥胖大鼠睾丸生殖细胞线粒体损伤的特点，探索线粒体损伤机制，并且开展线粒体损伤的膳食性保护因素研究，为肥胖男性生殖功能研究提供新的思路，为从膳食角度提高肥胖男性生殖功能提供科学依据。

肥胖是重要的公共卫生问题，肥胖不仅增加糖尿病、心脑血管疾病等的发病风险，而且与目前全球重点关注的男性生殖功能降低也密切相关，这成为肥胖领域的一个新热点。目前肥胖生殖研究集中在精子损伤和睾酮激素水平降低两方面，并且与肥胖的脂代谢紊乱和氧化损伤有关，但是，未见肥胖导致男性生殖功能低下的线粒体损伤机制研究。我们通过人群调查、患者线粒体损伤检测，以及成年和幼年肥胖模型动物实验验证了"肥胖导致男性生殖功能低下的机制是睾丸线粒体氧化损伤"的科学假设。在此基础上，观察了父系、母系肥胖对子代大鼠生理功能和生殖功能影响的研究，为肥胖男性生殖功能研究提供新的思路，为了解亲代肥胖对子代生理、生殖和肥胖风险提供科学依据。