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恒河猴卵母细胞和胚胎中的线粒体DNA缺失

Mitochondrial DNA deletions in rhesus macaque oocytes and embryos.

作者信息

Gibson T C, Kubisch H M, Brenner C A

机构信息

Department of Biological Sciences, University of New Orleans, New Orleans, LA 70122, USA.

出版信息

Mol Hum Reprod. 2005 Nov;11(11):785-9. doi: 10.1093/molehr/gah227. Epub 2005 Dec 22.

Abstract

Mitochondria are the most abundant organelles in mammalian oocytes and early embryos. Mitochondrial DNA (mtDNA) mutations, including the common deletion, have been found in skeletal muscle fibres from aged rhesus macaques. The specific aims of this study were to determine whether the mitochondrial common deletion is present in rhesus oocytes after hormonal stimulation and in embryos generated by in vitro production, or whether this deletion is already present in the immature oocyte. Using a nested primer PCR strategy, we found a significant increase in the proportion of mtDNA deletions in stimulated oocytes and embryos from rhesus macaques, compared with mtDNA deletions in immature, unstimulated oocytes derived from necropsied ovaries of age-matched monkeys. The common deletion is larger in the rhesus (5704 bp) than in humans (4977 bp). Accumulation of mtDNA deletions in oocytes may contribute to mitochondrial dysfunction and impaired ATP production. We propose the rhesus to be an excellent model to assess the quality of gametes and embryos and their developmental competence in primates, including humans.

摘要

线粒体是哺乳动物卵母细胞和早期胚胎中数量最多的细胞器。在老年恒河猴的骨骼肌纤维中发现了线粒体DNA(mtDNA)突变,包括常见缺失。本研究的具体目的是确定激素刺激后的恒河猴卵母细胞以及体外产生的胚胎中是否存在线粒体常见缺失,或者这种缺失是否在未成熟卵母细胞中就已存在。使用巢式引物PCR策略,我们发现与来自年龄匹配猴子尸检卵巢的未成熟、未受刺激卵母细胞中的mtDNA缺失相比,恒河猴受刺激卵母细胞和胚胎中mtDNA缺失的比例显著增加。恒河猴的常见缺失(5704 bp)比人类(4977 bp)更大。卵母细胞中mtDNA缺失的积累可能导致线粒体功能障碍和ATP生成受损。我们认为恒河猴是评估灵长类动物(包括人类)配子和胚胎质量及其发育能力的优秀模型。

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