Offspring sex impacts DNA methylation and gene expression in placentae from women with diabetes during pregnancy.
Offspring sex impacts DNA methylation and gene expression in placentae from women with diabetes during pregnancy.
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DOI：
10.1371/journal.pone.0190698
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Pinney SE
中科院分区：
文献类型：
--
作者：
Alexander J;Teague AM;Chen J;Aston CE;Leung YK;Chernausek S;Simmons RA;Pinney SE
我们假设妊娠期糖尿病（DDP）改变了胎盘中全基因组DNA甲基化，导致代谢相关基因的差异甲基化位点以及RNA和蛋白质表达的下游变化。我们采用巢式病例对照设计（n = 17对），使用Infinium 450 K人类甲基化珠芯片对来自美洲土著和西班牙裔DDP妇女的足月胎儿胎盘进行全基因组DNA甲基化定位。通过RNA-Seq和蛋白质印迹分析RNA表达和蛋白质水平。全基因组DNA甲基化分析显示，雄性后代有465个CpG位点发生显著变化，雌性后代有247个，两性后代有277个（p<0.001）。与暴露于DDP的雄性后代胎盘相比，雌性后代胎盘DNA甲基化显著增加的可能性高40%（p<0.001）。DNA甲基化的变化对应于6个基因的RNA和蛋白质水平的变化：PIWIL 3、CYBA、GSTM 1、GSTM 5、KCNE 1和NXN。在与线粒体功能、DNA修复、炎症、氧化应激相关的位点检测到差异DNA甲基化。这些发现开始解释了DDP母亲后代肥胖和2型糖尿病风险增加的机制。
We hypothesized that diabetes during pregnancy (DDP) alters genome-wide DNA methylation in placenta resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression. We mapped genome-wide DNA methylation with the Infinium 450K Human Methylation Bead Chip in term fetal placentae from Native American and Hispanic women with DDP using a nested case-control design (n = 17 pairs). RNA expression and protein levels were assayed via RNA-Seq and Western Blot. Genome-wide DNA methylation analysis revealed 465 CpG sites with significant changes for male offspring, 247 for female offspring, and 277 for offspring of both sexes (p<0.001). Placentae from female offspring were 40% more likely to have significant gains in DNA methylation compared with placentae from male offspring exposed to DDP (p<0.001). Changes in DNA methylation corresponded to changes in RNA and protein levels for 6 genes: PIWIL3, CYBA, GSTM1, GSTM5, KCNE1 and NXN. Differential DNA methylation was detected at loci related to mitochondrial function, DNA repair, inflammation, oxidative stress. These findings begin to explain mechanisms responsible for the increased risk for obesity and type 2 diabetes in offspring of mothers with DDP.
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影响因子：
5.7
作者：
Binder AM;LaRocca J;Lesseur C;Marsit CJ;Michels KB
通讯作者：
Michels KB
影响因子：
1.7
作者：
Jirkovská, M;Kubínová, L;Karen, P
通讯作者：
Karen, P
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
4.2
作者：
Chen, Xinhua;Scholl, Theresa O
通讯作者：
Scholl, Theresa O
影响因子：
4.4
作者：
Kurooka, H;Kato, K;Honjo, T
通讯作者：
Honjo, T