Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.
ECOGENE-21 Biocluster, Chicoutimi, QC, Canada.
J Dev Orig Health Dis. 2020 Aug;11(4):369-378. doi: 10.1017/S204017441900076X. Epub 2019 Nov 22.
Placental lipids transfer is essential for optimal fetal development, and alterations of these mechanisms could lead to a higher risk of adverse birth outcomes. Low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), and scavenger receptor class B type 1 (SCARB1) genes are encoding lipoprotein receptors expressed in the placenta where they participate in cholesterol exchange from maternal to fetal circulation. The aim of this study was thus to investigate the association between maternal lipid changes occurring in pregnancy, placental DNA methylation (DNAm) variations at LDLR, LRP1, and SCARB1 gene loci, and newborn's anthropometric profile at birth. Sixty-nine normoglycemic women were followed from the first trimester of pregnancy until delivery. Placental DNAm was quantified at 43 Cytosine-phosphate-Guanines (CpGs) at LDLR, LRP1, and SCARB1 gene loci using pyrosequencing: 4 CpGs were retained for further analysis. Maternal clinical data were collected at each trimester of pregnancy. Newborns' data were collected from medical records. Statistical models included minimally newborn sex and gestational and maternal age. Maternal total cholesterol changes during pregnancy (ΔT3-T1) were correlated with DNAm variations at LDLR (r = -0.32, p = 0.01) and LRP1 (r = 0.34, p = 0.007). DNAm at these loci was also correlated with newborns' cord blood triglyceride and leptin levels. Mediation analysis supports a causal relationship between maternal cholesterol changes, DNAm levels at LRP1 locus, and cord blood leptin concentration (pmediation = 0.02). These results suggest that LRP1 DNAm link maternal blood cholesterol changes in pregnancy and offspring adiposity at birth, which provide support for a better follow-up of blood lipids in pregnancy.
胎盘脂质转运对于胎儿的最佳发育至关重要，而这些机制的改变可能会增加不良出生结局的风险。低密度脂蛋白受体（LDLR）、低密度脂蛋白受体相关蛋白 1（LRP1）和清道夫受体 B 类 1 型（SCARB1）基因编码在胎盘表达的脂蛋白受体，它们参与胆固醇从母体向胎儿循环的交换。因此，本研究旨在探讨妊娠期间母体脂质变化与 LDLR、LRP1 和 SCARB1 基因座胎盘 DNA 甲基化（DNAm）变化以及新生儿出生时人体测量特征之间的关系。69 名血糖正常的孕妇从妊娠早期开始一直随访到分娩。使用焦磷酸测序技术在 LDLR、LRP1 和 SCARB1 基因座定量分析了 43 个胞嘧啶磷酸鸟嘌呤（CpG）的胎盘 DNAm：保留了 4 个 CpG 进行进一步分析。在每个妊娠阶段收集了母体临床数据。从病历中收集了新生儿的数据。统计模型包括新生儿性别、胎龄和母亲年龄的最小二乘。妊娠期间总胆固醇的变化（ΔT3-T1）与 LDLR（r = -0.32，p = 0.01）和 LRP1（r = 0.34，p = 0.007）的 DNAm 变化相关。这些基因座的 DNAm 也与新生儿脐带血甘油三酯和瘦素水平相关。中介分析支持母体胆固醇变化、LRP1 基因座的 DNAm 水平与脐带血瘦素浓度之间的因果关系（p 中介= 0.02）。这些结果表明，LRP1 DNAm 将妊娠期间母体血液胆固醇变化与出生时后代的肥胖联系起来，为更好地监测妊娠期间的血脂提供了支持。
