Govindaraj Vijayakumar, Krishnagiri Harshini, Chakraborty Payal, Vasudevan Madavan, Rao A Jagannadha
a Department of Biochemistry , Indian Institute of Science , Bangalore , India.
b Bionivid Technology Private Limited , Bangalore , India.
Syst Biol Reprod Med. 2017 Feb;63(1):37-48. doi: 10.1080/19396368.2016.1267820. Epub 2017 Jan 3.
Women are born with millions of primordial follicles which gradually decrease with increasing age and this irreversible supply of follicles completely exhausts at menopause. The fertility capacity of women diminishes in parallel with aging. The mechanisms for reproductive aging are not fully understood. We have observed a decline in Brca1 mediated DNA repair in aging rat primordial follicles. To further understand the age-related molecular changes, we performed microarray gene expression analysis using total RNA extracted from immature (18 to 20 day old) and aged (400 to 450 day old) rat primordial follicles. The results of current microarray study revealed that there were 1,011 (>1.5 fold, p<0.05) genes differentially expressed between two groups in which 422 genes were up-regulated and 589 genes were down-regulated in aged rat primordial follicles compared to immature primordial follicles. The gene ontology and pathway analysis of differentially expressed genes revealed a critical biological function such as cell cycle, oocyte meiosis, chromosomal stability, transcriptional activity, DNA replication, and DNA repair were affected by age. This considerable difference in gene expression profiles may have an adverse influence on oocyte quality. Our data provide information on the processes that may contribute to aging and age-related decline in fertility.
女性出生时带有数百万个原始卵泡，这些卵泡会随着年龄的增长而逐渐减少，并且这种不可逆的卵泡供应在绝经时会完全耗尽。女性的生育能力会随着年龄增长而下降。生殖衰老的机制尚未完全了解。我们观察到衰老大鼠原始卵泡中Brca1介导的DNA修复功能下降。为了进一步了解与年龄相关的分子变化，我们使用从未成熟（18至20日龄）和老龄（400至450日龄）大鼠原始卵泡中提取的总RNA进行了微阵列基因表达分析。当前微阵列研究的结果显示，两组之间有1011个（>1.5倍，p<0.05）基因差异表达，其中与未成熟原始卵泡相比，老龄大鼠原始卵泡中有422个基因上调，589个基因下调。对差异表达基因的基因本体和通路分析显示，细胞周期、卵母细胞减数分裂、染色体稳定性、转录活性、DNA复制和DNA修复等关键生物学功能受到年龄的影响。基因表达谱的这种显著差异可能会对卵母细胞质量产生不利影响。我们的数据提供了有关可能导致衰老和与年龄相关的生育能力下降过程的信息。
