In the overweight or obese female, reproductive complications include poor oocyte quality, decreased fecundity, gestational diabetes, and higher risk of reproductive cancers. Using lean and hyperphagia-induced obese female mice aged 10 weeks, we determined that the ovary from obese female mice had elevated (P < 0.10) levels of ataxia telangiectasia mutated (ATM) protein in oocytes of both small and large follicles. Phosphorylated ATM at serine 1981 was greater (P < 0.05) in large relative to small follicles with no additional impact of obesity. Obesity increased (P < 0.05) γH2AX in small follicles in obese relative to lean ovaries, while large follicles of both lean and obese mice had detectable levels of γH2AX. Cleaved caspase 3 was reduced (P < 0.05) in the small follicles of obese relative to lean ovaries. In large follicles of lean mice, cleaved caspase 3 was increased in large compared to small follicles (P < 0.05) but this pattern was absent in obese mice. Breast cancer type 1 susceptibility protein (BRCA1) or the phosphorylated BRCA1 proteins were observably altered by obesity. These data demonstrate that markers of DNA damage and repair have a follicle-dependent stage location and that obesity alters ATM and cleaved caspase 3 in a follicular stage dependent manner.

中文翻译：

---

肥胖改变卵巢 DNA 损伤反应和凋亡蛋白

在超重或肥胖女性中，生殖并发症包括卵母细胞质量差、生育力下降、妊娠糖尿病和生殖癌症风险增加。使用 10 周龄的瘦肉和食欲过盛诱导的肥胖雌性小鼠，我们确定肥胖雌性小鼠的卵巢在小卵泡和大卵泡的卵母细胞中均升高了 (P < 0.10) 共济失调毛细血管扩张突变 (ATM) 蛋白水平。1981 年丝氨酸磷酸化 ATM 较大（P < 0.05）相对于没有肥胖额外影响的小卵泡而言。与瘦卵巢相比，肥胖的小卵泡中的 γH2AX 增加（P < 0.05），而瘦和肥胖小鼠的大卵泡均具有可检测水平的 γH2AX。与瘦卵巢相比，肥胖的小卵泡中裂解的 caspase 3 减少 (P < 0.05)。在瘦小鼠的大卵泡中，与小卵泡相比，大卵泡中裂解的 caspase 3 增加（P < 0.05），但在肥胖小鼠中不存在这种模式。乳腺癌 1 型易感蛋白 (BRCA1) 或磷酸化的 BRCA1 蛋白可观察到因肥胖而改变。这些数据表明 DNA 损伤和修复的标志物具有依赖于卵泡的阶段位置，并且肥胖以依赖于卵泡阶段的方式改变 ATM 和裂解的 caspase 3。