Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome.
Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome.
复制标题
高雄激素血症改变多囊卵巢综合征肥胖小鼠卵母细胞中的线粒体结构和功能。
DOI：
10.1016/j.xfss.2020.12.001
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Blesson CS
中科院分区：
文献类型：
--
作者：
Chappell NR;Zhou B;Hosseinzadeh P;Schutt A;Gibbons WE;Blesson CS
在肥胖的多囊卵巢综合征（PCOS）小鼠模型中，高雄激素血症导致卵母细胞的葡萄糖/胰岛素代谢以及线粒体结构和功能改变，这在一定程度上解释了在PCOS中观察到的不良结局和遗传模式。
通过在一个成熟的经典PCOS小鼠模型中研究线粒体结构和功能来考察卵母细胞质量。
使用肥胖的PCOS小鼠模型与对照组进行动物研究。
在一家三级医疗大学医院环境中的动物研究设施
C57/B6J小鼠
3周龄的小鼠皮下植入双氢睾酮控释药丸或安慰剂，持续90天。
通过进行葡萄糖耐量试验、糖化血红蛋白（HbA1c）水平、体重和发情周期分析来验证小鼠模型。随后分离卵母细胞，并用于研究线粒体膜电位、氧化应激、脂质过氧化、三磷酸腺苷（ATP）产生、线粒体DNA拷贝数、转录本丰度、组织学和电子显微镜检查。
结果显示葡萄糖不耐受和高胰岛素血症以及发情周期失调。对卵母细胞的分析表明，线粒体内膜功能受损，ATP产生增加和线粒体DNA拷贝数增加，RNA转录本丰度改变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严重受损。
肥胖的PCOS小鼠模型显示出与线粒体功能受损相关的卵母细胞质量下降。
Hyperandrogenemia in an obese PCOS mouse model results in altered glucose/insulin metabolism and mitochondrial structure and function in the oocytes, in part explaining adverse outcomes and inheritance patterns seen in PCOS. To study the oocyte quality by means of mitochondrial structure and function in a well-established classic PCOS mouse model. Animal study using an obese PCOS mouse model compared with control. Animal research facility in a tertiary care university hospital setting C57/B6J mice Three week old mice had subdermal implants of DHT controlled release pellet or placebo for 90 days. The mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were subsequently isolated and were used to investigate mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance, histology and electron microscopy. Results showed glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of the oocytes demonstrated impaired inner mitochondrial membrane function, increased ATP production and mtDNA copy number, altered RNA transcript abundance and aberrant ovarian histology. Electron microscopy of the oocytes showed severely impaired mitochondrial ultrastructure. The obese PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial function.