Ovarian ageing: the role of mitochondria in oocytes and follicles
Ovarian ageing: the role of mitochondria in oocytes and follicles
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DOI：
10.1093/humupd/dmw028
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发表时间：
2016-11-01
影响因子：
13.3
通讯作者：
Reynier, Pascal
中科院分区：
文献类型：
--
作者：
May-Panloup, Pascale;Boucret, Lisa;Reynier, Pascal
卵巢衰老有很大的个体差异，几乎20%的不孕不育患者有卵巢早衰的迹象。这一特点，再加上现代社会的晚育，导致与年龄相关的卵巢功能障碍的出现，同时伴有怀孕的欲望。在卵巢老化的情况下，辅助生殖技术往往无效，从而增加了手术的经济、医疗和社会成本。卵巢老化的特点是卵巢卵母细胞储备的数量和质量的改变。线粒体在卵泡闭锁中起着核心作用，可能是决定卵母细胞质量受衰老不利影响的卵浆因子的主要目标。事实上，卵母细胞是体内线粒体中最丰富的细胞，在很大程度上依赖于这些细胞器获得受精和早期胚胎发育的能力。此外，卵母细胞确保了线粒体基因组的单代传递和稳定性。这篇综述的重点是线粒体在卵巢衰老中所起的作用，以及对几代人可能产生的后果。使用PubMed检索MEDLINE数据库，查找有关动物和人类线粒体和卵巢衰老的同行评议的原创文章和评论。搜索使用属于三组的关键词：“线粒体”或“线粒体DNA”；“卵巢储备”、“卵母细胞”、“卵巢”或“积云细胞”；还有“衰老”或“卵巢衰老”。这些关键词与其他与主题相关的搜索短语组合在一起。这些文章的参考文献被用来获取其他文章。在哺乳动物模型和人类中，线粒体和随着年龄增长而下降的卵母细胞质量之间有着密切的关系。从质量上讲，衰老相关的线粒体（mt） DNA不稳定导致卵母细胞中mtDNA突变的积累，在能力和线粒体异常遗传给后代的风险方面，在卵母细胞质量的恶化中起着关键作用。相反，一些mtDNA单倍群对卵巢储备能力的下降具有保护作用。从数量上讲，线粒体生物发生在卵子发生过程中至关重要，因为它构成了一个足够大的线粒体池，以允许正常的早期胚胎发育，并避免线粒体生物发生的过早激活。卵巢老化也严重影响周围颗粒细胞中线粒体生物发生的动态性质，这可能为卵母细胞质量提供有趣的替代生物标志物。更全面地了解线粒体在与卵巢老化有关的不孕症中的作用，将有助于未来更好地管理这种疾病。
There is a great inter-individual variability of ovarian ageing, and almost 20% of patients consulting for infertility show signs of premature ovarian ageing. This feature, taken together with delayed childbearing in modern society, leads to the emergence of age-related ovarian dysfunction concomitantly with the desire for pregnancy. Assisted reproductive technology is frequently inefficacious in cases of ovarian ageing, thus raising the economic, medical and societal costs of the procedures.Ovarian ageing is characterized by quantitative and qualitative alteration of the ovarian oocyte reserve. Mitochondria play a central role in follicular atresia and could be the main target of the ooplasmic factors determining oocyte quality adversely affected by ageing. Indeed, the oocyte is the richest cell of the body in mitochondria and depends largely on these organelles to acquire competence for fertilization and early embryonic development. Moreover, the oocyte ensures the uniparental transmission and stability of the mitochondrial genome across the generations. This review focuses on the role played by mitochondria in ovarian ageing and on the possible consequences over the generations.PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews concerning mitochondria and ovarian ageing, in animal and human species. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA'; 'ovarian reserve', 'oocyte', 'ovary' or 'cumulus cells'; and 'ageing' or 'ovarian ageing'. These keywords were combined with other search phrases relevant to the topic. References from these articles were used to obtain additional articles.There is a close relationship, in mammalian models and humans, between mitochondria and the decline of oocyte quality with ageing. Qualitatively, ageing-related mitochondrial (mt) DNA instability, which leads to the accumulation of mtDNA mutations in the oocyte, plays a key role in the deterioration of oocyte quality in terms of competence and of the risk of transmitting mitochondrial abnormalities to the offspring. In contrast, some mtDNA haplogroups are protective against the decline of ovarian reserve. Quantitatively, mitochondrial biogenesis is crucial during oogenesis for constituting a mitochondrial pool sufficiently large to allow normal early embryonic development and to avoid the untimely activation of mitochondrial biogenesis. Ovarian ageing also seriously affects the dynamic nature of mitochondrial biogenesis in the surrounding granulosa cells that may provide interesting alternative biomarkers of oocyte quality.A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future.