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大龄生育对后代大鼠海马体基因表达的影响。

Effects of delayed motherhood on hippocampal gene expression in offspring rats.

作者信息

Duan Ping, Li Bo, Li Caifang, Han Xuefei, Xu Yan, Xing Ying, Yan Wenhai

机构信息

Department of Basic Medicine, Institute of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Mol Cell Biochem. 2015 Jul;405(1-2):89-95. doi: 10.1007/s11010-015-2399-x. Epub 2015 May 15.

DOI:10.1007/s11010-015-2399-x
PMID:25976665
Abstract

While many studies have examined the pregnancy and health-related outcomes of delayed motherhood for women, less is known concerning the potential consequences for their children. This study aims to investigate the effect of delayed motherhood on the hippocampus at the whole genome level. Sprague-Dawley rat females, either at the age of 3 or 12 months, were individually housed with a randomly selected 3-month-old male. The rat whole genome expression chips were used to detect gene expression differences in the hippocampus of newborn rats. The gene expression profile was studied through gene ontology and signal pathway analyses. qRT-PCR was used to determine the mRNA expression of solute carrier family 2 (SLC2A1) and S-phase kinase-associated protein 2 (SKP2). Western blot was used to detect the protein expression of SKP2. Compared to the control group, 1291 differentially expressed genes were detected, including 635 up-regulated genes and 656 down-regulated genes. These differential expressed genes were involved in 110 significant biological process and nine significant signaling pathways, in which the pathway in cancer is the most changed pathway. For SKP2 (up-regulated) and SLC2A1 (up-regulated) genes which were relevant to the pathway in cancer, qRT-PCR results were consistent with gene chip assay results. The upregulation of SKP2 was also demonstrated at protein level. In conclusion, delayed motherhood led to unique patterns of hippocampal gene expression in offspring and the newly identified genes afford a quantitative view of the changes which enable deeper insights into the molecular basis underlying the role of delayed motherhood.

摘要

虽然许多研究已经考察了女性推迟生育对妊娠及健康相关的影响,但对于其子女可能产生的后果却知之甚少。本研究旨在从全基因组水平探究推迟生育对海马体的影响。将3月龄或12月龄的斯普拉格-道利雌性大鼠单独饲养,并与随机挑选的3月龄雄性大鼠合笼。使用大鼠全基因组表达芯片检测新生大鼠海马体中的基因表达差异。通过基因本体论和信号通路分析对基因表达谱进行研究。采用qRT-PCR法测定溶质载体家族2(SLC2A1)和S期激酶相关蛋白2(SKP2)的mRNA表达。采用蛋白质免疫印迹法检测SKP2的蛋白表达。与对照组相比,共检测到1291个差异表达基因,其中上调基因635个,下调基因6,56个。这些差异表达基因参与了110个显著的生物学过程和9条显著的信号通路,其中癌症通路是变化最大的通路。对于与癌症通路相关的SKP2(上调)和SLC2A1(上调)基因,qRT-PCR结果与基因芯片检测结果一致。SKP2的上调在蛋白水平也得到证实。总之,推迟生育导致子代海马体基因表达出现独特模式,新鉴定出的基因提供了这些变化的定量视图,有助于更深入地了解推迟生育作用的分子基础。

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