Department of Anatomy and Developmental Biology, Monash University, Clayton Campus, Bldg. 76, Victoria 3800 Australia.
Am J Physiol Heart Circ Physiol. 2011 Feb;300(2):H645-51. doi: 10.1152/ajpheart.00689.2010. Epub 2010 Nov 12.
Prenatal exposure to high levels of ethanol is associated with cardiac malformations, but the effects of lower levels of exposure on the heart are unclear. Our aim was to investigate the effects of daily exposure to ethanol during late gestation, when cardiomyocytes are undergoing maturation, on the developing myocardium. Pregnant ewes were infused with either ethanol (0.75 g/kg) or saline for 1 h each day from gestational days 95 to 133 (term ∼145 days); tissues were collected at 134 days. In sheep, cardiomyocytes mature during late gestation as in humans. Within the left ventricle (LV), cardiomyocyte number was determined using unbiased stereology and cardiomyocyte size and nuclearity determined using confocal microscopy. Collagen deposition was quantified using image analysis. Genes relating to cardiomyocyte proliferation and apoptosis were examined using quantitative real-time PCR. Fetal plasma ethanol concentration reached 0.11 g/dL after EtOH infusions. Ethanol exposure induced significant increases in relative heart weight, relative LV wall volume, and cardiomyocyte cross-sectional area. Ethanol exposure advanced LV maturation in that the proportion of binucleated cardiomyocytes increased by 12%, and the number of mononucleated cardiomyocytes was decreased by a similar amount. Apoptotic gene expression increased in the ethanol-exposed hearts, although there were no significant differences between groups in total cardiomyocyte number or interstitial collagen. Daily exposure to a moderate dose of ethanol in late gestation accelerates the maturation of cardiomyocytes and increases cardiomyocyte and LV tissue volume in the fetal heart. These effects on cardiomyocyte growth may program for long-term cardiac vulnerability.
产前暴露于高水平的乙醇与心脏畸形有关，但低水平暴露对心脏的影响尚不清楚。我们的目的是研究在妊娠晚期（当心肌细胞正在成熟时）每天暴露于乙醇对发育中的心肌的影响。妊娠母羊每天接受 0.75 克/公斤乙醇或生理盐水输注 1 小时，从妊娠第 95 天到 133 天（足月约 145 天）；在 134 天时收集组织。在绵羊中，心肌细胞在妊娠晚期像在人类中一样成熟。在左心室（LV）内，使用无偏立体学确定心肌细胞数量，并使用共聚焦显微镜确定心肌细胞大小和核数。使用图像分析定量胶原沉积。使用定量实时 PCR 检查与心肌细胞增殖和凋亡相关的基因。在 EtOH 输注后，胎儿血浆乙醇浓度达到 0.11 克/分升。乙醇暴露导致相对心脏重量、相对 LV 壁体积和心肌细胞横截面积显著增加。乙醇暴露加速 LV 成熟，双核心肌细胞的比例增加了 12%，单核心肌细胞的数量减少了相似的数量。尽管在总心肌细胞数量或间质胶原方面，各组之间没有显著差异，但乙醇暴露的心脏中凋亡基因的表达增加。妊娠晚期每日暴露于中等剂量的乙醇加速了心肌细胞的成熟，并增加了胎儿心脏中的心肌细胞和 LV 组织体积。这些对心肌细胞生长的影响可能会导致长期的心脏脆弱性。
