Maternal vitamin D deficiency impairs heart formation in mouse offspring

Cardiac heart diseases are the most common congenital diseases. The origins of these diseases are still largely unknown. Environmental factors including nutrition of mothers are now emerging as major causes of these developmental pathologies.Vitamin D deficiency has become a public health burden all over the word. Since maternal 25-hydroxyvitamin D (25(OH)D) determined fetal and neonatal 25(OH)D status, we reasoned that foetuses exposed to insufficient levels of vitamin D, may feature developmental defects. We thus investigated in mice the impact of vitamin D deficiency of the mothers on embryonic cardiac development of the offsprings. Using whole genome transcriptomic, ChIP-seq, ChIP-loop and echocardiography, we found that that E16.5 embryos of mother deficient in vitamin D featured hypertrophic heart revealed by a thicker left ventricular wall and septum. The hypertrophy develops in the adult and even in the second generation of mice. We further uncovered that a change in 3D genome landscape was responsible for embryonic heart defects and likely for a transgenerational continuity of the disease.