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饮食和基因突变诱发的肥胖都会影响小鼠的卵母细胞质量。

Both diet and gene mutation induced obesity affect oocyte quality in mice.

作者信息

Hou Yan-Jun, Zhu Cheng-Cheng, Duan Xing, Liu Hong-Lin, Wang Qiang, Sun Shao-Chen

机构信息

College of Animal Science and Technology, Nanjing Agriculture University, Nanjing, 210095, China.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.

出版信息

Sci Rep. 2016 Jan 6;6:18858. doi: 10.1038/srep18858.

Abstract

Obesity was shown to cause reproductive dysfunctions such as reduced conception, infertility and early pregnancy loss. However, the possible effects of obesity on oocyte quality are still not fully understood. In this study we investigated the effects of both diet and gene mutation induced obesity on impairments in mouse oocyte polarization, oxidative stress, and epigenetic modifications. Our results showed that high-fat diet induced obesity (HFD) and gene mutation induced obesity (ob/ob) could both impair oocyte meiotic maturation, disrupt spindle morphology, and reduce oocyte polarity. Oocytes from obese mice underwent oxidative stress, as shown by high DHE and ROS levels. Abnormal mitochondrial distributions and structures were observed in oocytes from obese groups of mice and early apoptosis signals were detected, which suggesting that oxidative stress had impaired mitochondrial function and resulted in oocyte apoptosis. Our results also showed that 5 mC levels and H3K9 and H3K27 methylation levels were altered in oocytes from obese mice, which indicated that DNA methylation and histone methylation had been affected. Our results showed that both HFD and ob/ob induced obesity affected oocyte maturation and that oxidative stress-induced early apoptosis and altered epigenetic modifications may be the reasons for reduced oocyte quality in obese mice.

摘要

肥胖已被证明会导致生殖功能障碍,如受孕率降低、不孕和早期妊娠丢失。然而,肥胖对卵母细胞质量的潜在影响仍未完全了解。在本研究中,我们调查了饮食诱导肥胖和基因突变诱导肥胖对小鼠卵母细胞极化、氧化应激和表观遗传修饰受损的影响。我们的结果表明,高脂饮食诱导肥胖(HFD)和基因突变诱导肥胖(ob/ob)均可损害卵母细胞减数分裂成熟、破坏纺锤体形态并降低卵母细胞极性。肥胖小鼠的卵母细胞经历了氧化应激,高脱氢表雄酮(DHE)和活性氧(ROS)水平表明了这一点。在肥胖组小鼠的卵母细胞中观察到线粒体分布和结构异常,并检测到早期凋亡信号,这表明氧化应激损害了线粒体功能并导致卵母细胞凋亡。我们的结果还表明,肥胖小鼠卵母细胞中的5-甲基胞嘧啶(5 mC)水平以及组蛋白H3赖氨酸9(H3K9)和组蛋白H3赖氨酸27(H3K27)甲基化水平发生了改变,这表明DNA甲基化和组蛋白甲基化受到了影响。我们的结果表明,HFD和ob/ob诱导的肥胖均影响卵母细胞成熟,氧化应激诱导的早期凋亡和表观遗传修饰改变可能是肥胖小鼠卵母细胞质量下降的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f243/4702149/c467fd72aeb8/srep18858-f1.jpg

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