The role of mitophagy during oocyte aging in human, mouse, and Drosophila: implications for oocyte quality and mitochondrial disease.

Reproduction & Fertility Pub Date : 2021-10-11 eCollection Date: 2021-12-01 DOI:10.1530/RAF-21-0060
Rachel T Cox, Joanna Poulton, Suzannah A Williams
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引用次数: 8

Abstract

There is a worldwide trend for women to have their first pregnancy later in life. However, as oocyte quality declines with maternal aging, this trend leads to an increase in subfertility. The cellular mechanisms underlying this decline in oocyte competence are poorly understood. Oocyte mitochondria are the subcellular organelles that supply the energy that drives early embryogenesis, and thus their quality is critical for successful conception. Mitochondria contain their own DNA (mtDNA) and mutations in mtDNA cause mitochondrial diseases with severe symptoms, such as neurodegeneration and heart disease. Since mitochondrial function declines in tissues as humans age accompanied by an accumulation of mtDNA mutations, mtDNA is implicated as a cause of declining oocyte quality in older mothers. While this mutation load could be caused by declining accuracy of the mitochondrial replisome, age-related decline in mitochondrial quality control likely contributes, however knowledge is lacking. Mitophagy, a cellular process which specifically targets and recycles damaged mitochondria may be involved, but studies are scarce. And although assisted reproductive technologies can help older mothers, how these techniques affect the mechanisms that regulate mitochondrial and oocyte quality have not been studied. With the long-term goal of understanding the molecular mechanisms that control mitochondrial quality in the oocyte, model systems including Drosophila and mouse as well as human oocytes have been used. In this review, we explore the contribution of mitophagy to oocyte quality and the need for further systematic investigation in oocytes during maternal aging using different systems.

Lay summary: Mitochondria are small parts of cells called organelles that generate the chemical energy needed for life. Hundreds of thousands of mitochondria in the developing eggs of the mother support the initial growth and development of the fertilized egg. However, due to increasingly diminished function over time, mitochondria generate less energy as we age, posing real problems for older women considering pregnancy. It is possible that this declining energy could be responsible for declining fertility as women age. Energy may decline because mitochondria fail and the cell's way of keeping them healthy become less efficient as we age. This review summarizes what is known about mitochondrial quality control in developing eggs as they age. In the future, understanding how the best mitochondria are selected and maintained in the egg, and hence the future baby, may enable older women with or without mitochondrial problems, to have healthy children.

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线粒体自噬在人类、小鼠和果蝇卵母细胞衰老过程中的作用:对卵母细胞质量和线粒体疾病的影响。
女性晚育是一个世界性的趋势。然而,随着母亲年龄的增长,卵母细胞质量下降,这种趋势导致生育能力低下的增加。这种卵母细胞能力下降的细胞机制尚不清楚。卵母细胞线粒体是提供早期胚胎发生能量的亚细胞细胞器,因此其质量对成功受孕至关重要。线粒体含有自己的DNA (mtDNA), mtDNA的突变会导致线粒体疾病,症状严重,如神经变性和心脏病。由于随着人类年龄的增长,线粒体功能在组织中下降,并伴随着mtDNA突变的积累,mtDNA被认为是老年母亲卵母细胞质量下降的原因之一。虽然这种突变负荷可能是由线粒体复制体的准确性下降引起的,但与年龄相关的线粒体质量控制下降可能是原因之一,但缺乏相关知识。线粒体自噬,一种专门针对和循环受损线粒体的细胞过程,可能参与其中,但研究很少。虽然辅助生殖技术可以帮助老年母亲,但这些技术如何影响调节线粒体和卵母细胞质量的机制还没有研究。为了了解控制卵母细胞线粒体质量的分子机制,包括果蝇和小鼠以及人类卵母细胞在内的模型系统已经被使用。在这篇综述中,我们探讨了线粒体自噬对卵母细胞质量的贡献,以及在母体衰老过程中使用不同系统对卵母细胞进行进一步系统研究的必要性。概要:线粒体是细胞中被称为细胞器的一小部分,它产生生命所需的化学能。母亲发育中的卵子中有数十万个线粒体支持受精卵的初始生长和发育。然而,随着时间的推移,线粒体的功能越来越弱,随着年龄的增长,线粒体产生的能量越来越少,这给考虑怀孕的老年妇女带来了真正的问题。随着女性年龄的增长,这种能量的下降可能是导致生育率下降的原因。能量可能会下降,因为线粒体失效,随着年龄的增长,细胞保持它们健康的方式变得不那么有效。这篇综述总结了线粒体质量控制在卵子老化过程中的已知情况。在未来,了解最好的线粒体是如何在卵子中被选择和维持的,因此未来的婴儿,可能使有或没有线粒体问题的老年妇女有健康的孩子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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