Morrison J L, Botting K J, Dyer J L, Williams S J, Thornburg K L, McMillen I C
Center for the Early Origins of Adult Health, Discipline of Physiology, University of Adelaide, Adelaide, SA, Australia.
Am J Physiol Regul Integr Comp Physiol. 2007 Jul;293(1):R306-13. doi: 10.1152/ajpregu.00798.2006. Epub 2007 Apr 11.
Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause of intrauterine growth restriction (IUGR) and increased neonatal morbidity. Fetal adaptations to placental restriction maintain the growth of key organs, including the heart, but the impact of these adaptations on individual cardiomyocytes is unknown. Placental and hence fetal growth restriction was induced in fetal sheep by removing the majority of caruncles in the ewe before mating (placental restriction, PR). Vascular surgery was performed on 13 control and 11 PR fetuses at 110-125 days of gestation (term: 150 +/- 3 days). PR fetuses with a mean gestational Po(2) < 17 mmHg were defined as hypoxic. At postmortem (<135 or >135 days), fetal hearts were collected, and cardiomyocytes were isolated and fixed. Proliferating cardiomyocytes were counted by immunohistochemistry of Ki67 protein. Cardiomyocytes were stained with methylene blue to visualize the nuclei, and the proportion of mononucleated cells and length and width of cardiomyocytes were measured. PR resulted in chronic fetal hypoxia, IUGR, and elevated plasma cortisol concentrations. Although there was no difference in relative heart weights between control and PR fetuses, there was an increase in the proportion of mononucleated cardiomyocytes in PR fetuses. Whereas mononucleated and binucleated cardiomyocytes were smaller, the relative size of cardiomyocytes when expressed relative to heart weight was larger in PR compared with control fetuses. The increase in the relative proportion of mononucleated cardiomyocytes and the relative sparing of the growth of individual cardiomyocytes in the growth-restricted fetus are adaptations that may have long-term consequences for heart development in postnatal life.
胎盘功能不全导致胎儿底物供应受限，是宫内生长受限（IUGR）及新生儿发病率增加的主要原因。胎儿对胎盘受限的适应性变化维持了包括心脏在内的关键器官的生长，但这些适应性变化对单个心肌细胞的影响尚不清楚。在母羊交配前切除大部分肉阜，诱导胎羊发生胎盘及胎儿生长受限（胎盘受限，PR）。在妊娠110 - 125天（足月：150±3天）对13只对照胎儿和11只PR胎儿进行血管手术。平均妊娠Po(2) < 17 mmHg的PR胎儿被定义为缺氧。在死后（<135天或>135天），收集胎儿心脏，分离并固定心肌细胞。通过Ki67蛋白免疫组化计数增殖心肌细胞。用亚甲蓝对心肌细胞染色以观察细胞核，测量单核细胞比例、心肌细胞长度和宽度。PR导致慢性胎儿缺氧、IUGR及血浆皮质醇浓度升高。虽然对照胎儿和PR胎儿的相对心脏重量无差异，但PR胎儿单核心肌细胞比例增加。虽然单核和双核心肌细胞较小，但与对照胎儿相比，PR胎儿中心肌细胞相对于心脏重量的相对大小更大。生长受限胎儿中单核心肌细胞相对比例增加以及单个心肌细胞生长相对保留，这些适应性变化可能对出生后心脏发育产生长期影响。
