Houde A A, St-Pierre J, Hivert M F, Baillargeon J P, Perron P, Gaudet D, Brisson D, Bouchard L
1 Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Qc, Canada.
2 ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, Qc, Canada.
J Dev Orig Health Dis. 2014 Apr;5(2):132-41. doi: 10.1017/S2040174414000038.
Placental lipoprotein lipase (LPL) is crucial for placental lipid transfer. Impaired LPL gene expression and activity were reported in pregnancies complicated by gestational diabetes mellitus (GDM) and intra-uterine growth restriction. We hypothesized that placental LPL DNA methylation is altered by maternal metabolic status and could contribute to fetal programming. The objective of this study was thus to assess whether placental LPL DNA methylation is associated with GDM and both maternal and newborn lipid profiles. Placenta biopsies were sampled at delivery from 126 women including 27 women with GDM diagnosed following a post 75 g-oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. Placental LPL DNA methylation and expression levels were determined using bisulfite pyrosequencing and quantitative real-time PCR, respectively. DNA methylation levels within LPL proximal promoter region (CpG1) and intron 1 CpG island (CpGs 2 and 3) were lower in placenta of women with GDM. DNA methylation levels at LPL-CpG1 and CpG3 were also negatively correlated with maternal glucose (2-h post OGTT; r=-0.22; P=0.02) and HDL-cholesterol levels (third trimester of pregnancy; r=-0.20; p=0.03), respectively. Moreover, we report correlation between LPL-CpG2 DNA methylation and cord blood lipid profile. DNA methylation levels within intron 1 CpG island explained up to 26% (r⩽-0.51; P<0.001) of placental LPL mRNA expression variance. Overall, we showed that maternal metabolic profile is associated with placental LPL DNA methylation dysregulation. Our results suggest that site-specific LPL epipolymorphisms in the placenta are possibly functional and could potentially be involved in determining the future metabolic health of the newborn.
胎盘脂蛋白脂肪酶（LPL）对胎盘脂质转运至关重要。据报道，在合并妊娠期糖尿病（GDM）和宫内生长受限的妊娠中，LPL基因表达和活性受损。我们推测胎盘LPL DNA甲基化会因母体代谢状态而改变，并可能导致胎儿编程。因此，本研究的目的是评估胎盘LPL DNA甲基化是否与GDM以及母体和新生儿脂质谱相关。在分娩时从126名妇女中采集胎盘活检样本，其中包括27名在妊娠24至28周期间进行75 g口服葡萄糖耐量试验（OGTT）后被诊断为GDM的妇女。分别使用亚硫酸氢盐焦磷酸测序和定量实时PCR测定胎盘LPL DNA甲基化和表达水平。GDM妇女胎盘中LPL近端启动子区域（CpG1）和内含子1 CpG岛（CpGs 2和3）内的DNA甲基化水平较低。LPL-CpG1和CpG3处DNA甲基化水平也分别与母体葡萄糖（OGTT后2小时；r = -0.22；P = 0.02）和高密度脂蛋白胆固醇水平（妊娠晚期；r = -0.20；p = 0.03）呈负相关。此外，我们报告了LPL-CpG2 DNA甲基化与脐血脂质谱之间的相关性。内含子1 CpG岛内的DNA甲基化水平解释了胎盘LPL mRNA表达变异的高达26%（r⩽-0.51；P < 0.001）。总体而言，我们表明母体代谢谱与胎盘LPL DNA甲基化失调相关。我们的结果表明，胎盘中位点特异性LPL表观多态性可能具有功能，并可能潜在地参与决定新生儿未来的代谢健康。
