Leeuwerke Mariëtte, Eilander Michelle S, Pruis Maurien G M, Lendvai Ágnes, Erwich Jan Jaap H M, Scherjon Sicco A, Plösch Torsten, Eijsink Jasper J H
Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Biol Reprod. 2016 Feb;94(2):37. doi: 10.1095/biolreprod.115.131698. Epub 2016 Jan 6.
Variations in DNA methylation levels in the placenta are thought to influence gene expression and are associated with complications of pregnancy, like fetal growth restriction (FGR). The most important cause for FGR is placental dysfunction. Here, we examined whether changes in DNA methylation, followed by gene expression changes, are mechanistically involved in the etiology of FGR. In this retrospective case-control study, we examined the association between small-for-gestational-age (SGA) children and both DNA methylation and gene expression levels of the genes WNT2, IGF2/H19, SERPINA3, HERVWE1, and PPARG in first-trimester placental tissue. We also examined the repetitive element LINE-1. These candidate genes have been reported in the literature to be associated with SGA. We used first-trimester placental tissue from chorionic villus biopsies. A total of 35 SGA children (with a birth weight below the 10th percentile) were matched to 70 controls based on their gestational age. DNA methylation levels were analyzed by pyrosequencing and mRNA levels were analyzed by real-time PCR. None of the average DNA methylation levels, measured for each gene, showed a significant difference between SGA placental tissue compared to control tissue. However, hypermethylation of WNT2 was detected on two CpG positions in SGA. This was not associated with changes in gene expression. Apart from two CpG positions of the WNT2 gene, in early placenta samples, no evident changes in DNA methylation or expression were found. This indicates that the already reported changes in term placenta are not present in the early placenta, and therefore must arise after the first trimester.
胎盘DNA甲基化水平的变化被认为会影响基因表达，并与妊娠并发症有关，如胎儿生长受限（FGR）。FGR的最重要原因是胎盘功能障碍。在此，我们研究了DNA甲基化变化继之以基因表达变化是否在FGR的病因学中具有机制性作用。在这项回顾性病例对照研究中，我们检测了小于胎龄（SGA）儿童与孕早期胎盘组织中WNT2、IGF2/H19、SERPINA3、HERVWE1和PPARG基因的DNA甲基化及基因表达水平之间的关联。我们还检测了重复元件LINE-1。这些候选基因在文献中已被报道与SGA相关。我们使用了绒毛取样获得的孕早期胎盘组织。总共35名SGA儿童（出生体重低于第10百分位数）根据其孕周与70名对照进行匹配。通过焦磷酸测序分析DNA甲基化水平，通过实时PCR分析mRNA水平。对于每个基因所测量的平均DNA甲基化水平，SGA胎盘组织与对照组织之间均未显示出显著差异。然而，在SGA中检测到WNT2基因两个CpG位点的高甲基化。这与基因表达变化无关。除了WNT2基因的两个CpG位点外，在早期胎盘样本中未发现DNA甲基化或表达有明显变化。这表明已报道的足月胎盘变化在早期胎盘中不存在，因此必定在孕早期之后出现。
