Division of Neonatology, Augusta University, Augusta, GA, Georgia.
Department of Pathology, Augusta University, Augusta, GA, Georgia.
Pediatr Res. 2018 Oct;84(4):537-544. doi: 10.1038/s41390-018-0069-x. Epub 2018 Jun 2.
Maternal nutrient restriction (MNR) is a widespread cause of fetal growth restriction (FGR), an independent predictor of heart disease and cardiovascular mortality. Our objective was to examine the developmental and long-term impact of MNR-induced FGR on cardiac structure in a model that closely mimics human development.
A reduction in total caloric intake spanning pregestation through to lactation in guinea pig sows was used to induce FGR. Proliferation, differentiation, and apoptosis of cardiomyocytes were assessed in late-gestation fetal, neonatal, and adult guinea pig hearts. Proteomic analysis and pathway enrichment were performed on fetal hearts.
Cardiomyocyte proliferation and the number of mononucleated cells were enhanced in the MNR-FGR fetal and neonatal heart, suggesting a delay in cardiomyocyte differentiation. In fetal hearts of MNR-FGR animals, apoptosis was markedly elevated and the total number of cardiomyocytes reduced, the latter remaining so throughout neonatal and into adult life. A reduction in total cardiomyocyte number in adult MNR-FGR hearts was accompanied by exaggerated hypertrophy and a disorganized architecture. Pathway analysis identified genes related to cell proliferation, differentiation, and survival.
FGR influences cardiomyocyte development during critical windows of development, leading to a permanent deficiency in cardiomyocyte number and compensatory hypertrophy in a rodent model that recapitulates human development.
母体营养限制（MNR）是胎儿生长受限（FGR）的一个广泛原因，FGR 是心脏病和心血管死亡率的独立预测因子。我们的目的是在一个紧密模拟人类发育的模型中，研究 MNR 诱导的 FGR 对心脏结构的发育和长期影响。
通过减少受孕前至哺乳期的总热量摄入，来诱导豚鼠母猪的 FGR。评估晚期胎儿、新生儿和成年豚鼠心脏中的心肌细胞增殖、分化和凋亡。对胎儿心脏进行蛋白质组学分析和通路富集。
MNR-FGR 胎儿和新生儿心脏中的心肌细胞增殖和单核细胞数量增加，表明心肌细胞分化延迟。在 MNR-FGR 动物的胎儿心脏中，凋亡明显增加，总心肌细胞数量减少，这种情况一直持续到新生儿期和成年期。成年 MNR-FGR 心脏中心肌细胞总数减少伴随着心肌肥厚和组织结构紊乱。通路分析确定了与细胞增殖、分化和存活相关的基因。
FGR 在发育的关键窗口期影响心肌细胞的发育，导致啮齿动物模型中心肌细胞数量永久性不足和代偿性肥厚，该模型模拟了人类的发育。
