Ghaffari Neda, Parry Samuel, Elovitz Michal A, Durnwald Celeste P
Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, Maternal and Child Health Research Program, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania.
AJP Rep. 2016 Oct;6(4):e430-e435. doi: 10.1055/s-0036-1597652.
The epigenetic mechanisms underlying fetal metabolic programming are poorly understood. We studied whether obesity is associated with alterations in placental miRNA expression. A cross-sectional study was performed, including (1) normal-weight women (BMI 20-24.9 kg/m) and normal-birth-weight (BW) infants (2,700-3,500 g) ( = 20), (2) normal-weight and macrosomic infants (BW ≥ 4,000 g) ( = 10), (3) obese (BMI ≥ 35 kg/m) and normal BW infants ( = 16), and (4) obese and macrosomic infants ( = 10). All had term deliveries (37-41 weeks) and normal glucose tolerance (1 hour GCT < 7.2 mmol/L [130 mg/dL]). The expression of 5,639 placental miRNAs was assessed using miRNA microarray. Differential miRNA expression was determined using two-way ANOVA and pairwise contrasts, with the Benjamini-Hochberg (BH) correction. MiRNAs with Z-scores ≥ 2 and false discovery rate (FDR) < 20% were considered significant. Principal components analysis demonstrated similar global miRNA expression profiles among groups. Of 5,639 miRNAs, only 5 were significantly different between obese and controls, which were not validated by quantitative polymerase reaction. There was no difference in placental miRNA expression associated with obesity or overgrowth. Aberrant placental miRNA expression is an unlikely mechanism underlying fetal metabolic programming related to maternal obesity.
胎儿代谢编程背后的表观遗传机制目前仍知之甚少。我们研究了肥胖是否与胎盘微小RNA（miRNA）表达的改变有关。
我们进行了一项横断面研究，研究对象包括：（1）体重正常的女性（体重指数[BMI]为20 - 24.9 kg/m²）及出生体重正常（BW）的婴儿（2700 - 3500 g）（n = 20）；（2）体重正常但婴儿为巨大儿（BW≥4000 g）（n = 10）；（3）肥胖（BMI≥35 kg/m²）且婴儿出生体重正常（n = 16）；以及（4）肥胖且婴儿为巨大儿（n = 10）。所有研究对象均为足月分娩（37 - 41周）且葡萄糖耐量正常（1小时血糖筛查试验[GCT] < 7.2 mmol/L [130 mg/dL]）。使用miRNA微阵列评估了5639种胎盘miRNA的表达。采用双向方差分析和两两对比法确定miRNA的差异表达，并进行Benjamini - Hochberg（BH）校正。Z分数≥2且错误发现率（FDR）< 20%的miRNA被认为具有显著性差异。
主成分分析表明，各组之间的整体miRNA表达谱相似。在5639种miRNA中，肥胖组与对照组之间仅有5种存在显著差异，但未通过定量聚合酶反应验证。
与肥胖或胎儿过度生长相关的胎盘miRNA表达没有差异。胎盘miRNA表达异常不太可能是与母体肥胖相关的胎儿代谢编程的潜在机制。
