Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart
Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart
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DOI：
10.1113/jp275806
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发表时间：
2018-06-15
影响因子：
5.5
通讯作者：
Morrison, Janna L.
中科院分区：
文献类型：
--
作者：
Darby, Jack R. T.;McMillen, I. Caroline;Morrison, Janna L.
胎儿暴露于一系列环境压力因素（包括母亲营养不良）与成年后死于心血管疾病的风险增加有关。本研究旨在确定妊娠晚期母体营养限制对调节胎儿心脏生长和发育的分子机制的影响。母亲营养不良导致妊娠晚期胎儿葡萄糖浓度下降，而对照组和妊娠晚期营养不良 (LGUN) 组的胎儿动脉 PO2 保持不变。有证据表明 LGUN 组胎儿右心室中 IGF2/IGF2R 信号通过 CAMKII 通路上调，表明肥大信号增加。 LGUN 还导致胎儿心脏右心室中 COL1A、TIMP1 和 TIMP3 mRNA 表达增加。此外，胎儿葡萄糖浓度与COL1A表达之间存在反比关系。通过对右心室天狼星红染色切片的定量，证实了 LGUN 组心脏存在间质纤维化。因此，我们发现，妊娠晚期母亲营养不良可能会促进胎儿右心室心肌重塑的发生，从而对以后生活中的右心室功能和心脏健康产生负面影响。
Exposure of the fetus to a range of environmental stressors, including maternal undernutrition, is associated with an increased risk of death from cardiovascular disease in adult life. This study aimed to determine the effect of maternal nutrient restriction in late gestation on the molecular mechanisms that regulate cardiac growth and development of the fetal heart. Maternal undernutrition resulted in a decrease in fetal glucose concentrations across late gestation, whilst fetal arterial PO2 remained unchanged between the control and late gestation undernutrition (LGUN) groups. There was evidence of an up-regulation of IGF2/IGF2R signalling through the CAMKII pathway in the fetal right ventricle in the LGUN group, suggesting an increase in hypertrophic signalling. LGUN also resulted in an increased mRNA expression of COL1A, TIMP1 and TIMP3 in the right ventricle of the fetal heart. In addition, there was an inverse relationship between fetal glucose concentrations and COL1A expression. The presence of interstitial fibrosis in the heart of the LGUN group was confirmed through the quantification of picrosirius red-stained sections of the right ventricle. We have therefore shown that maternal undernutrition in late gestation may drive the onset of myocardial remodelling in the fetal right ventricle and thus has negative implications for right ventricle function and cardiac health in later life.