School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Department of Psychology, Durham University, Durham, DH1 3LE, UK.
Sci Rep. 2017 Sep 25;7(1):12272. doi: 10.1038/s41598-017-11129-9.
The developmental timeline of the human heart remains elusive. The heart takes on its characteristic four chambered appearance by ~56 days gestational age (DGA). However, owing to the complexities (both technical and logistical) of exploring development in utero, we understand little of how the ventricular walls develop. To address this, we employed diffusion tensor magnetic resonance imaging to explore the architecture and tissue organization of the developing heart aged 95-143 DGA. We show that fractional anisotropy increases (from ~0.1 to ~0.5), diffusion coefficients decrease (from ~1 × 10mm/sec to ~0.4 × 10mm/sec), and fiber paths, extracted by tractography, increase linearly with gestation, indicative of the increasing organization of the ventricular myocytes. By 143 DGA, the developing heart has the classical helical organization observed in mature mammalian tissue. This was accompanied by an increase in connexin 43 and connexin 40 expression levels, suggesting their role in the development of the ventricular conduction system and that electrical propagation across the heart is facilitated in later gestation. Our findings highlight a key developmental window for the structural organization of the fetal heart.
人类心脏的发育时间表仍然难以捉摸。心脏在大约 56 天的孕龄（DGA）时呈现出其特有的四腔外观。然而，由于在子宫内探索发育的复杂性（包括技术和后勤方面），我们对心室壁如何发育知之甚少。为了解决这个问题，我们采用弥散张量磁共振成像来探索 95-143 DGA 发育中的心脏的结构和组织。我们发现各向异性分数增加（从约 0.1 增加到约 0.5），扩散系数降低（从约 1×10mm/sec 降低到约 0.4×10mm/sec），并且通过追踪纤维路径提取的纤维路径呈线性增加，这表明心室肌细胞的组织不断增加。到 143 DGA 时，发育中的心脏具有在成熟哺乳动物组织中观察到的经典螺旋组织。这伴随着连接蛋白 43 和连接蛋白 40 表达水平的增加，表明它们在心室传导系统的发育中的作用，以及在妊娠后期心脏的电传播得到促进。我们的研究结果突出了胎儿心脏结构组织的关键发育窗口。
