NAD deficiency due to environmental factors or gene–environment interactions causes congenital malformations and miscarriage in mice
Hartmut Cuny, Melissa Rapadas, Jessica M. Gereis, Ella MMA Martin, Rosemary B. Kirk, Hongjun Shi, Sally L. Dunwoodie
Abstract
, which alone does not cause NAD deficiency or malformations, the incidence of embryo loss and malformations was significantly higher, suggesting a gene-environment interaction. Maternal and embryonic NAD levels were deficient. Mild hypoxia as an additional factor exacerbated the embryo outcome. Our data show that NAD deficiency as a cause of embryo loss and congenital malformation is not restricted to the rare cases of biallelic mutations in NAD synthesis pathway genes. Instead, monoallelic genetic variants and environmental factors can result in similar outcomes. The results expand our understanding of the causes of congenital malformations and the importance of sufficient NAD precursor consumption during pregnancy.