University Hospital Copenhagen, Rigshospitalet, Fertility Clinic, Copenhagen, Denmark.
Hum Reprod. 2010 Apr;25(4):957-68. doi: 10.1093/humrep/deq014. Epub 2010 Feb 10.
The development competence of human oocytes declines with increasing age. The objective of this study was to investigate the effect of age on gene expression profile in mature human oocytes.
mRNA was isolated for whole genome gene expression microarray analysis from metaphase II (MII) oocytes donated by IVF or ICSI patients [10 women aged <36 years (younger) and five women aged 37-39 years (both inclusive) (older)] undergoing controlled ovarian stimulation. The oocytes were donated and prepared immediately after recovery from the follicle. RT-PCR on additional four younger and two older oocytes confirmed the array analysis.
On the basis of 15 independent replicates of single MII oocytes, 7470 genes (10 428 transcripts) were identified as present in the MII oocytes. Of these, 342 genes showed a significantly different expression level between the two age groups; notably, genes annotated to be involved in cell cycle regulation, chromosome alignment (e.g. MAD2L1 binding protein), sister chromatid separation (e.g. separase), oxidative stress and ubiquitination. The top signaling network affected by age was 'cell cycle and organism development' (e.g. SMAD2 and activin B1 receptor).
There is a substantial difference between younger and older oocytes in the transcriptional level of genes involved in central biological functions of the oocytes, thus providing information on processes that may be associated with the ageing phenomenon and possibly contributing to decreased fertility.
人类卵母细胞的发育能力随年龄的增长而下降。本研究旨在探讨年龄对成熟人类卵母细胞基因表达谱的影响。
从接受控制性卵巢刺激的体外受精或卵胞浆内单精子注射患者捐献的中期 II（MII）卵母细胞中分离 mRNA，进行全基因组基因表达微阵列分析[10 名年龄<36 岁（年轻）和 5 名年龄 37-39 岁（含）（年老）]。这些卵母细胞是在从卵泡中恢复后立即捐献和准备的。对另外 4 个年轻和 2 个年老的卵母细胞进行 RT-PCR 验证了芯片分析。
基于 15 个独立的单个 MII 卵母细胞重复实验，鉴定出 7470 个存在于 MII 卵母细胞中的基因（10428 个转录本）。其中，342 个基因在两个年龄组之间的表达水平有显著差异；值得注意的是，注释为参与细胞周期调控、染色体排列（如 MAD2L1 结合蛋白）、姐妹染色单体分离（如分离酶）、氧化应激和泛素化的基因。受年龄影响的顶级信号网络是“细胞周期和生物体发育”（如 SMAD2 和激活素 B1 受体）。
在参与卵母细胞中心生物学功能的基因的转录水平上，年轻和年老的卵母细胞之间存在显著差异，从而为可能与衰老现象相关并可能导致生育能力下降的过程提供了信息。
