Chromosome segregation errors in oocytes lead to the production of aneuploid eggs, which are the leading cause of pregnancy loss and of several congenital diseases such as Down syndrome. The frequency of chromosome segregation errors in oocytes increases with maternal age, especially at a late stage of reproductive life. How aging at various life stages affects oocytes differently remains poorly understood. In this study, we describe aging-associated changes in the transcriptome profile of mouse oocytes throughout reproductive life. Our single-oocyte comprehensive RNA sequencing using RamDA-seq revealed that oocytes undergo transcriptome changes at a late reproductive stage, whereas their surrounding cumulus cells exhibit transcriptome changes at an earlier stage. Calorie restriction, a paradigm that reportedly prevents aging-associated egg aneuploidy, promotes a transcriptome shift in oocytes with the up-regulation of genes involved in chromosome segregation. This shift is accompanied by the improved maintenance of chromosomal cohesin, the loss of which is a hallmark of oocyte aging and causes chromosome segregation errors. These findings have implications for understanding how oocytes undergo aging-associated functional decline throughout their reproductive life in a context-dependent manner.

中文翻译：

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单卵母细胞转录组分析揭示了受生命阶段和卡路里限制影响的衰老相关效应

卵母细胞中的染色体分离错误导致产生非整倍体卵子，这是导致流产和唐氏综合症等几种先天性疾病的主要原因。卵母细胞中染色体分离错误的频率随着母亲年龄的增加而增加，尤其是在生殖生命的后期。不同生命阶段的衰老如何不同地影响卵母细胞仍然知之甚少。在这项研究中，我们描述了小鼠卵母细胞在整个生殖生命周期中与衰老相关的转录组变化。我们使用 RamDA-seq 进行的单卵母细胞综合 RNA 测序显示，卵母细胞在生殖后期经历转录组变化，而其周围的卵丘细胞在早期阶段表现出转录组变化。卡路里限制，据报道，一种预防与衰老相关的卵子非整倍体的范例，通过上调参与染色体分离的基因来促进卵母细胞中的转录组转变。这种转变伴随着染色体凝聚素的改善维持，其丧失是卵母细胞老化的标志并导致染色体分离错误。这些发现对于了解卵母细胞如何在其生殖生命中以环境相关的方式经历与衰老相关的功能衰退具有重要意义。