Regulatory role of m⁶A epitranscriptomic modifications in normal development and congenital malformations during...

The discovery of N6-methyladenosine (m⁶A) methylation and its role in translation has led to the emergence of a new field of research. Despite accumulating evidence suggesting that m⁶A methylation is essential for the pathogenesis of cancers and aging diseases by influencing RNA stability, localization, transformation, and translation efficiency, its role in normal and abnormal embryonic development remains unclear. An increasing number of studies are addressing the development of the nervous and gonadal systems during embryonic development, but only few are assessing that of the immune, hematopoietic, urinary, and respiratory systems. Additionally, these studies are limited by the requirement for reliable embryonic animal models and the difficulty in collecting tissue samples of fetuses during development. Multiple studies on the function of m⁶A methylation have used suitable cell lines to mimic the complex biological processes of fetal development or the early postnatal phase; hence, the research is still in the primary stage. Herein, we discuss current advances in the extensive biological functions of m⁶A methylation in the development and maldevelopment of embryos/fetuses and conclude that m⁶A modification occurs extensively during fetal development. Aberrant expression of m⁶A regulators is probably correlated with single or multiple defects in organogenesis during the intrauterine life. This comprehensive review will enhance our understanding of the pivotal role of m⁶A modifications involved in fetal development and examine future research directions in embryogenesis.