Chappell Neil R, Zhou Beth, Schutt Amy K, Gibbons William E, Blesson Chellakkan S
N Chappell, Obstetrics and Gynecology, Baylor College of Medicine, Houston, United States.
B Zhou, Obstetrics and Gynecology, Baylor College of Medicine, Houston, United States.
Endocr Connect. 2020 Feb 1;9(3):261-70. doi: 10.1530/EC-19-0553.
Polycystic ovary syndrome (PCOS) is the most common ovulatory defect in women. Although most PCOS patients are obese, a subset of PCOS women are lean but show similar risks for adverse fertility outcomes. A lean PCOS mouse model was created using prenatal androgen administration. This developmentally programmed mouse model was used for this study. Our objective was to investigate if mitochondrial structure and functions were compromised in oocytes obtained from lean PCOS mouse. The lean PCOS mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were isolated and were used to investigate inner mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance, histology and electron microscopy. Our results demonstrate that lean PCOS mice has similar weight to that of the controls but exhibited glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of their oocytes show impaired inner mitochondrial membrane function, elevated reactive oxygen species (ROS), increased RNA transcript abundance and aberrant ovarian histology. Electron microscopy of the oocytes showed impaired mitochondrial ultrastructure. In conclusion, the lean PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial ultrastructure and function.
多囊卵巢综合征（PCOS）是女性中最常见的排卵缺陷。尽管大多数PCOS患者肥胖，但一部分瘦型PCOS女性却表现出相似的不良生育结局风险。通过产前给予雄激素建立了瘦型PCOS小鼠模型。本研究使用了这种发育程序编排的小鼠模型。我们的目的是研究从瘦型PCOS小鼠获得的卵母细胞中线粒体结构和功能是否受损。通过进行葡萄糖耐量试验、糖化血红蛋白水平、体重和动情周期分析，对瘦型PCOS小鼠模型进行了验证。分离卵母细胞并用于研究线粒体内膜电位、氧化应激、脂质过氧化、ATP生成、线粒体DNA拷贝数、转录本丰度、组织学和电子显微镜检查。我们的结果表明，瘦型PCOS小鼠的体重与对照组相似，但表现出葡萄糖不耐受、高胰岛素血症以及动情周期失调。对其卵母细胞的分析显示线粒体内膜功能受损、活性氧（ROS）水平升高、RNA转录本丰度增加以及卵巢组织学异常。卵母细胞的电子显微镜检查显示线粒体超微结构受损。总之，瘦型PCOS小鼠模型显示卵母细胞质量下降与线粒体超微结构和功能受损有关。
