Telomere Dynamics in Congenital Heart Defects: Hidden Architects of Cardiogenesis?

Congenital heart defects (CHDs) represent a significant global health burden, particularly in India, and are among the leading causes of childhood mortality. Despite growing insights into their multifactorial etiology, the molecular mechanisms linking maternal health to embryonic heart development remain elusive. Telomeres, the repetitive DNA-protein structures that cap chromosome ends, are recognized as markers of cellular aging and also as regulators of early embryogenesis. This review examines emerging evidence connecting telomere biology with the risk of CHD in offspring.

This review is aimed at mapping the existing evidence on telomere dynamics in the context of cardiogenesis and CHD. It encompasses studies involving human subjects and experimental models, focusing on telomere length (TL), telomerase activity, and telomere dysfunction in cardiac development and CHD pathogenesis.

We highlight the influence of environmental stressors on telomere dynamics and chromosomal stability in gametes and early embryos. Current evidence suggests that altered telomere dynamics may influence cardiomyocyte proliferation, cellular senescence, and genomic integrity, thereby contributing to aberrant cardiac development. Studies indicate potential associations between telomere shortening, impaired telomerase activity, and increased susceptibility to CHD; however, findings remain heterogeneous and fragmented.

This review highlights the need to explore impaired parental telomere maintenance as a novel risk factor for improper chromosomal segregation and abnormal heart development. Understanding the role of telomere dynamics in cardiogenesis may provide novel insights into the molecular mechanisms underlying CHD. This could aid in identifying potential biomarkers for early risk assessment and open avenues for targeted therapeutic strategies aimed at modulating telomere function.

Telomere biology represents a promising yet underexplored area in CHD research. This study is among the first to conceptualize impaired parental and embryonic telomere dynamics as a unifying mechanistic link in CHD pathogenesis. This review highlights the need for comprehensive and integrative studies to elucidate potential mechanistic links in order to translate these findings into clinical applications. Understanding this telomere-CHD axis may open a new frontier for periconceptional intervention and targeted maternal care to improve overall birth outcomes.