Roland Marie Cecilie Paasche, Godang Kristin, Aukrust Pål, Henriksen Tore, Lekva Tove
National Advisory Unit for Women's Health, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Department of Obstetrics, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Sci Rep. 2021 Mar 18;11(1):6213. doi: 10.1038/s41598-021-85777-3.
Cholesteryl ester transfer protein (CETP) regulates high density lipoproteins (HDL)-cholesterol (C) and HDL-C is essential for fetal development. We hypothesized that women giving birth to large-for-gestational-age (LGA) and small-for-gestational age (SGA) infants differed in longitudinal changes in lipoproteins, CETP activity and HDL-C and that placentas from women with higher or lower circulating HDL-C displayed differential expression of mRNAs involved in cholesterol/nutrient transport, insulin signaling, inflammation/ extracellular matrix (ECM) remodeling. Circulating lipids and CETP activity was measured during pregnancy, NMR lipidomics in late pregnancy, and associations with LGA and SGA infants investigated. RNA sequencing was performed in 28 placentas according to higher and lower maternal HDL-C levels. Lipidomics revealed high triglycerides in large VLDL and lipids/cholesterol/cholesteryl esters in small HDL in women giving birth to SGA infants. Placentas from women with higher HDL-C had decreased levels of CETP expression which was associated with mRNAs involved in cholesterol/nutrient transport, insulin signaling and inflammation/ECM remodeling. Both placental and circulating CETP levels were associated with growth of the fetus. Low circulating CETP activity at 36-38 weeks was associated with giving birth to SGA infants. Our findings suggest a link between increased maternal HDL-C levels, low CETP levels both in circulation and placenta, and SGA infants.
胆固醇酯转运蛋白（CETP）调节高密度脂蛋白（HDL）胆固醇（C），而HDL-C对胎儿发育至关重要。我们假设，分娩适于胎龄儿（LGA）和小于胎龄儿（SGA）的女性在脂蛋白、CETP活性和HDL-C的纵向变化方面存在差异，并且循环HDL-C水平较高或较低的女性的胎盘在参与胆固醇/营养物质转运、胰岛素信号传导、炎症/细胞外基质（ECM）重塑的mRNA表达上存在差异。在孕期测量循环脂质和CETP活性，在妊娠晚期进行核磁共振脂质组学分析，并研究其与LGA和SGA婴儿的关联。根据母亲HDL-C水平的高低，对28个胎盘进行RNA测序。脂质组学显示，分娩SGA婴儿的女性中，大极低密度脂蛋白（VLDL）中的甘油三酯含量高，小HDL中的脂质/胆固醇/胆固醇酯含量高。HDL-C水平较高的女性的胎盘，其CETP表达水平降低，这与参与胆固醇/营养物质转运、胰岛素信号传导和炎症/ECM重塑的mRNA有关。胎盘和循环中的CETP水平均与胎儿生长有关。妊娠36 - 38周时循环中CETP活性低与分娩SGA婴儿有关。我们的研究结果表明，母亲HDL-C水平升高、循环和胎盘中CETP水平降低与SGA婴儿之间存在联系。
