肥胖对雄性小鼠生育的影响及其机制研究

发布时间：2018-06-18 04:26

本文选题：肥胖 + 雄性生育力　；参考：《上海交通大学》2015年硕士论文

【摘要】：肥胖是一种可严重损害青少年和成人健康的综合代谢性疾病,其可诱发包括心血管疾病、2型糖尿病、高血压和癌症在内的多种疾病。尽管肥胖对女性生殖或者卵细胞发育的不良影响已成共识,但其对男性生育力的危害还尚未定论。本研究旨在于探索高脂饮食诱导的肥胖是否会损伤雄性生育力,并从动物模型上进一步揭示其作用机制。因此,我们首先给予雄性C57BL/6小鼠高脂喂养10周以建立起肥胖模型。实验的结果显示,与正常饲料喂养的雄鼠相比,肥胖雄鼠的精子活动力以及前向活动力显著下降,同时其精子畸形率明显上升。另外,肥胖小鼠精子的顶体反应发生率下降;与此同时,其雄激素水平下降,雌激素水平上升。由此可见,精子功能参数的改变有力地证明了肥胖雄鼠的生育力受到损伤,并且此结论也被与肥胖雄鼠合笼配对的实验后雌鼠其受孕率下降所证实。睾丸形态学的超微结构分析显示,肥胖鼠睾丸生精上皮严重空泡化,生精细胞间以及生精细胞与支持细胞间的细胞连接松散。进一步的Western blot分析表明:肥胖鼠睾丸中构成血睾屏障的相关蛋白occludin、ZO-1及androgen receptor显著降低,而囊泡运输相关蛋白clathrin显著升高,血睾屏障的完整性明显受损。综上所述,肥胖可致雄性小鼠精液中精子参数和性激素水平显著下降,其结果可导致小鼠生育力受损,而血睾屏障的破坏可能是肥胖影响雄性生育力机制中的一个重要环节。
[Abstract]:Obesity is a comprehensive metabolic disease that can seriously damage the health of adolescents and adults. It can induce many diseases, including cardiovascular disease, type 2 diabetes, hypertension and cancer. Although the adverse effects of obesity on women's reproductive or oocyte development have been agreed, the harm to male fertility has yet to be determined. The aim of this study was to explore whether obesity induced by high fat diet would damage male fertility and to reveal its mechanism from animal models. Therefore, we first gave male C57BL / 6 mice high fat feeding for 10 weeks to establish a obesity model. The results showed that the sperm motility and forward motility of obese male rats were significantly decreased and the sperm deformity rate was significantly higher than that of male rats fed with normal diet. In addition, the incidence of acrosome reaction in the spermatozoa of obese mice decreased, while the level of androgen decreased and the level of estrogen increased. It can be seen that the change of spermatozoa function parameters strongly proves that the fertility of obese male mice is damaged, and this conclusion is also confirmed by the decrease of pregnant rate of female mice after the experiment of matching with the obese male cage. The ultrastructural analysis of testicular morphology showed that the spermatogenic epithelium of obese rats was severely vacuolated and the connection between spermatogenic cells and Sertoli cells was loose. Further Western blot analysis showed that the related proteins occludinine ZO-1 and androgen receptor in the testis of obese rats were significantly decreased, while the vesicular transport related protein clathrin was significantly increased, and the integrity of the blood-testis barrier was significantly impaired. In conclusion, obesity can significantly decrease sperm parameters and sex hormone levels in male mice semen, and the results may lead to impaired fertility in mice. The destruction of blood testis barrier may be an important link in the mechanism of obesity affecting male fertility.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R589.2

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