Myocyte enlargement, differentiation, and proliferation kinetics in the fetal sheep heart
Myocyte enlargement, differentiation, and proliferation kinetics in the fetal sheep heart
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DOI：
10.1152/japplphysiol.00937.2006
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发表时间：
2007-03-01
影响因子：
3.3
通讯作者：
Faber, J. Job
中科院分区：
文献类型：
--
作者：
Jonker, Sonnet S.;Zhang, Lubo;Faber, J. Job
新的心肌细胞的产生是子宫内心脏生长的一个重要过程。大多数或全部心肌细胞在围产期通过终末分化过程丧失增殖能力。越来越多的研究集中在实验干预如何影响胎羊心肌细胞的生长。然而，关于胎儿心脏正常生长的基本问题仍然没有答案。在这项研究中，我们确定，在妊娠的最后三分之一胎羊的心脏主要是通过四个过程。1)心肌细胞增殖对每日心肌质量增加有很大贡献，心肌细胞数量持续增加至足月。2)从近似115天胎龄（dGA）到足月（145 dGA），与单核细胞向双核细胞转变（终末分化）相关的肌细胞大小增加对心脏生长的贡献（迄今未被认识）变得相当大。由于在类似于115 dGA之后，双核化成为肌细胞细胞周期活动的更常见结果，因此双核肌细胞的数量以单核肌细胞的数量为代价增加。在同一时期，心肌细胞核分裂之间的间隔和细胞周期活动的持续时间大幅减少。最后，心脏的生长部分是由于单核和双核肌细胞的增大，在妊娠的最后三分之一，它们的横截面直径增加，但长度没有增加。这些关于正常心脏生长的数据可能使我们能够更详细地了解产前实验和病理干预的后果。
The generation of new myocytes is an essential process of in utero heart growth. Most, or all, cardiac myocytes lose their capacity for proliferation during the perinatal period through the process of terminal differentiation. An increasing number of studies focus on how experimental interventions affect cardiac myocyte growth in the fetal sheep. Nevertheless, fundamental questions about normal growth of the fetal heart remain unanswered. In this study, we determined that during the last third of gestation the hearts of fetal sheep grew primarily by four processes. 1) Myocyte proliferation contributed substantially to daily cardiac mass gain, and the number of cardiac myocytes continued to increase to term. 2) The (hitherto unrecognized) contribution to cardiac growth by the increase in myocyte size associated with the transition from mononucleation to binucleation (terminal differentiation) became considerable from similar to 115 days of gestational age (dGA) until term (145dGA). Because binucleation became the more frequent outcome of myocyte cell cycle activity after similar to 115dGA, the number of binucleated myocytes increased at the expense of the number of mononucleated myocytes. Both the interval between nuclear divisions and the duration of cell cycle activity in myocytes decreased substantially during this same period. Finally, cardiac growth was in part due to enlargement of 3) mononucleated and 4) binucleated myocytes, which grew in cross-sectional diameter but not length during the last third of gestation. These data on normal cardiac growth may enable a more detailed understanding of the consequences of experimental and pathological interventions in prenatal life.