No evidence for age-related differences in mitochondrial RNA quality in the female germline.

Reproduction & Fertility Pub Date : 2022-09-16 Print Date: 2022-07-01 DOI:10.1530/RAF-22-0025
Fiona Hartley, Arwa Alageel, Ruth Appeltant, Nicki Gray, Emmanouela Repapi, Dagan Wells, Suzannah A Williams, Joanna Poulton
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Abstract

Abstract: Mitochondrial quality is implicated as a contributor to declining fertility with aging. We investigated mitochondrial transcripts in oocytes and their associated cumulus cells from mice of different ages using RNA-seq. Mice aged 3 weeks, 9 weeks, and 1 year were superovulated, and 48 h later, oocyte cumulus complexes were collected by follicle puncture. We did not detect any major differences that could be attributed to aging. However, mitochondrial RNA transcripts which deviated from the consensus sequence were found at a higher frequency in cumulus cells than in their corresponding oocyte. Previous investigations have shown that variation in the sequence of mtRNA transcripts is substantial, and at least some of this can be accounted for by post-transcriptional modifications which impact base calling during sequencing. Our data would be consistent with either less post-transcriptional modification in mitochondrial RNA from oocytes than cumulus cells or with lower mtDNA mutational load.

Lay summary: Women become less fertile as they age. Shortage of energy contributes to this, caused by a decline in the quality of mitochondria (the powerhouses of the cell) in the egg. Genes are the blueprint for the cell. They are made of DNA which is copied into an RNA message, or instructions, for making proteins. We counted differences in the RNA message of developing eggs and the cells that support them during development (cumulus cells). We compared the number of these differences in mice of different ages. These age groups represent mice had not reached puberty, those of prime reproductive age, and old mothers. We did not find any differences linked to the age of the mice. However, we did find differences between the egg and the cumulus cells. In most cases, there were lower levels of mutations in eggs than there were in cumulus cells.

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没有证据表明女性生殖系线粒体RNA质量存在年龄相关性差异。
图形摘要:摘要:线粒体质量与衰老导致生育能力下降有关。我们使用RNA-seq研究了不同年龄小鼠卵母细胞及其相关卵丘细胞中的线粒体转录物。对3周、9周和1岁的小鼠进行超排,48小时后,通过卵泡穿刺收集卵母细胞-卵丘复合体。我们没有发现任何可归因于衰老的主要差异。然而,与相应的卵母细胞相比,在卵丘细胞中发现偏离一致序列的线粒体RNA转录物的频率更高。先前的研究表明,mtRNA转录物序列的变化是显著的,至少其中一些可以通过转录后修饰来解释,转录后修饰会影响测序过程中的碱基调用。我们的数据要么与卵丘细胞相比,卵母细胞线粒体RNA的转录后修饰较少,要么与较低的线粒体DNA突变负荷一致。总结:随着年龄的增长,女性的生育能力会降低。由于卵子中线粒体(细胞的动力库)的质量下降,导致能量短缺。基因是细胞的蓝图。它们是由DNA组成的,DNA被复制成RNA信息或指令,用于制造蛋白质。我们统计了发育中的卵子和在发育过程中支持它们的细胞(卵丘细胞)的RNA信息的差异。我们比较了不同年龄小鼠的这些差异数量。这些年龄组代表了尚未进入青春期的小鼠、处于最佳生育年龄的小鼠和年老的母亲。我们没有发现任何与老鼠年龄有关的差异。然而,我们确实发现了卵子和卵丘细胞之间的差异。在大多数情况下,卵子中的突变水平低于卵丘细胞。
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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