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Two proteins may affect 1 in 10 miscarriages
As one in 10 miscarriages is believed to be caused by failure of the heart to form, identifying the precise timing of development of the four chambers increases our ability to monitor heart development in utero. According to new research, major structures of an neonatal heart form within a four day period. Lead investigator, Eleftheria Pervolaraki PhD, hopes her findings will assist doctors in identifying and eventually intervening when heart development is found failing.
"We have identified a critical time of development of the human heart in pregnancy and now have a map we can use to interpret problems in development, and look at ways of trying to resolve those problems."
Researchers imaged 23 fetal hearts between gestational ages 95 and 143 days, to reveal how the heart developes. Using MRI technology and algorithms written specifically for the procedure in conjunction with 3D computer software, researchers were able to watch the heart grow in a precise four day period at 124 days of pregnancy. Within this 4 day period, patterns of cardiac fibre direction are laid down forming the helix shape of the heart and its four chambers.
Dr Pervolaraki found a remarkable consistency in development between the 16 and 17 week point of pregnancy. The research team, which included collaborators at the Universities of Durham and Edinburgh, also identified increased levels of two proteins: connexin 40 and connexin 43 during the same period.
"The expression of connexin 40 and connexin 43 helps cells in the heart to communicate with each other. As the amount of these proteins increases, cells can 'speak' to each other more effectively."
The scientists acknowledge that currently a developmental timeline of the human heart remains an elusive tool for most physicans. Current available medical office technology can only effectively monitor a baby's heart after 20 weeks of pregnancy when developmental problems are difficult to resolve. However, researchers believe their specialist imaging techniques can be adapted for use in hospital clinics, allowing clinicians the ability to spot if a baby's heart is failing to form.
The study is published in the journal Nature Scientific Reports.
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 × 10-3mm2/sec to ~0.4 × 10-3mm2/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.
All authors: Eleftheria Pervolaraki, James Dachtler, Richard A. Anderson and Arun V. Holden
The research was funded by the Medical Research Council in the UK and the Lush Prize, a fund set up to promote non-animal research.
University of Leeds
The University of Leeds is one of the largest higher education institutions in the UK, with more than 33,000 students from more than 150 different countries, and a member of the Russell Group of research-intensive universities.
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The fetal heart at the end of the 4 day period when cardiac tissue becomes organised into a helix shape.
Image Credit: Dr Eleftheria Pervolaraki.