Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes
Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes
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DOI：
10.1113/jphysiol.2006.122200
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发表时间：
2007-04-15
影响因子：
5.5
通讯作者：
Thornburg, Kent L.
中科院分区：
文献类型：
--
作者：
Louey, Samantha;Jonker, Sonnet S.;Thornburg, Kent L.
绵羊脐胎盘栓塞术（UPE）已被用于研究胎盘功能不全对胎儿发育的影响。然而，它对心脏的具体影响却很少被研究。本研究的目的是确定UPE诱导的胎盘功能不全对心肌细胞大小、成熟和增殖的影响。植入仪器的胎羊进行了10或20天的UPE。在妊娠125 +/- 1天（10天组）或136 +/- 1天（20天组）（周期与145天相似）采集心脏。在分离的心肌细胞中测定细胞大小、成熟状态（通过双核肌细胞的比例测量）和细胞周期活性（通过细胞Ki-67阳性染色测量）。UPE胎儿低氧血症，但平均动脉压与对照组没有差异。UPE胎儿体重较对照组轻（10天：-21%，P < 0.05； 20天：-27%，P < 0.01），心脏较小，但心脏重量与体重相适应。在任何年龄，对照组和UPE心肌细胞的长度和宽度都没有差异。10天的UPE没有显著改变双核肌细胞的比例或两个心室的细胞周期活性。然而，20 d的UPE使双心室细胞周期活性降低了70% (P < 0.05)；该年龄UPE胎儿的双核肌细胞比例也较低（左心室：31.1 +/- 12.0比46.0 +/- 6.6%,P < 0.05；右心室：29.4 +/- 12.3比46.3 +/- 5.3%,P < 0.05）。由此得出结论，在没有胎儿动脉高血压的情况下，胎盘功能不全通过抑制心肌细胞的增殖和成熟与心脏生长的实质性抑制有关。
Umbilicoplacental embolization (UPE) in sheep has been used to investigate the effects of placental insufficiency on fetal development. However, its specific effects on the heart have been little studied. The aim of this study was to determine the effects of placental insufficiency, induced by UPE, on cardiomyocyte size, maturation and proliferation. Instrumented fetal sheep underwent UPE for either 10 or 20 days. Hearts were collected at 125 +/- 1 days (10 day group) or 136 +/- 1 days (20 day group) of gestation (term similar to 145 days). Cell size, maturational state (as measured by the proportion of binucleated myocytes) and cell cycle activity (as measured by positive staining of cells for Ki-67) were determined in dissociated cardiomyocytes. UPE fetuses were hypoxaemic, but mean arterial pressures were not different from controls. UPE fetuses were lighter than control fetuses (10 days: -21%, P < 0.05; 20 days: -27%, P < 0.01) and had smaller hearts, but heart weight was appropriate for body weight. Neither lengths nor widths were different between control and UPE cardiomyocytes at either age. Ten days of UPE did not significantly alter the proportion of binucleated myocytes or cell cycle activity in either ventricle. However, 20 days of UPE reduced cell cycle activity in both ventricles by similar to 70% (P < 0.05); the proportion of binucleated myocytes was also lower in UPE fetuses at this age (left ventricle: 31.1 +/- 12.0 versus 46.0 +/- 6.6%, P < 0.05; right ventricle: 29.4 +/- 12.3 versus 46.3 +/- 5.3%, P < 0.05). It is concluded that in the absence of fetal arterial hypertension, placental insufficiency is associated with substantially depressed growth of the heart through suppressed proliferation and maturation of cardiomyocytes.