Department of Paediatrics, University of Cambridge, Cambridge, U.K.
Diabetes. 2010 Jan;59(1):282-6. doi: 10.2337/db09-0757. Epub 2009 Sep 30.
We have hypothesized that variation in imprinted growth-promoting fetal genes may affect maternal glucose concentrations in pregnancy. To test this hypothesis we evaluated the effects of fetal disruption of murine H19(Delta13) on maternal glucose concentrations in pregnancy.
Experimental mice were pregnant females that had inherited the disrupted H19(Delta13) from their fathers and were therefore phenotypically wild type due to imprinting; approximately half of their litters were null for H19(Delta13) through maternal inheritance of the disrupted gene. In control mice approximately half the litter paternally inherited the disrupted H19(Delta13), so the pups were either genetically wild type or phenotypically wild type due to imprinting. Blood glucose concentrations were assessed by intraperitoneal glucose tolerance tests on days 1, 16, and 18 of pregnancy.
There were no differences in the glucose concentrations of control and experimental pregnant mice at day 1. However, at day 16 mothers carrying H19(Delta13)-null pups had a significantly higher area under the glucose tolerance test curves than controls (1,845 +/- 378 vs. 1,386 +/- 107 mmol * min * l(-1) [P = 0.01]) in association with increasing pregnancy-related insulin resistance. Although this difference lessened toward term, overall, mothers of maternally inherited H19(Delta13) mutants had significantly higher glucose concentrations during the last trimester (1,602 +/- 321 [n = 17] vs. 1,359 +/- 147 [n = 18] mmol * min * l(-1) [P = 0.009]).
This study provides evidence that maternal glucose concentrations in pregnant mice can be affected by targeted disruption of fetal H19(Delta13). This implies that variable fetal IGF2 expression could affect risk for gestational diabetes.
我们假设印记的促生长胎儿基因的变异可能会影响妊娠期间的母体葡萄糖浓度。为了验证这一假说，我们评估了小鼠 H19(Delta13) 对妊娠期间母体葡萄糖浓度的影响。
实验小鼠为妊娠雌性，它们从父亲那里继承了 H19(Delta13) 的缺失，因此由于印记而表型野生型；它们的大约一半后代由于母系遗传而缺失 H19(Delta13)。在对照小鼠中，大约一半的后代从父亲那里继承了缺失的 H19(Delta13)，因此由于印记，这些幼崽要么是遗传野生型，要么是表型野生型。通过在妊娠第 1、16 和 18 天进行腹腔内葡萄糖耐量试验来评估血糖浓度。
在妊娠第 1 天，对照和实验妊娠小鼠的血糖浓度没有差异。然而，在妊娠第 16 天，携带 H19(Delta13) 缺失幼崽的母亲的葡萄糖耐量试验曲线下面积显著高于对照组（1845+/-378 对 1386+/-107mmolminl(-1)[P=0.01]），与妊娠相关的胰岛素抵抗增加有关。尽管这种差异在接近足月时有所减轻，但总体而言，母系遗传 H19(Delta13) 突变体的母亲在妊娠晚期的血糖浓度明显较高（1602+/-321[n=17]对 1359+/-147[n=18]mmolminl(-1)[P=0.009]）。
这项研究提供了证据表明，妊娠小鼠的母体葡萄糖浓度可以受到胎儿 H19(Delta13) 靶向缺失的影响。这意味着可变的胎儿 IGF2 表达可能会影响妊娠糖尿病的风险。
