Bozon, Kayleigh and Cuny, Hartmut and Sheng, Delicia Z. and Sipka, Alena and Shand, Antonia W. and Nassar, Natasha and Dunwoodie, Sally L. (2025) Maternal Circulatory NAD Precursor Levels and the Yolk Sac Determine NAD Deficiency‐Driven Congenital Malformation Risk. The FASEB Journal, 39 (14). ISSN 0892-6638
Full text not available from this repository.Abstract
ABSTRACT
Nicotinamide adenine dinucleotide (NAD) is an essential cofactor in hundreds of cellular processes. Genetic disruption of NAD de novo synthesis causes congenital NAD deficiency disorder (CNDD), characterized by multiple congenital malformations or death in utero. Patient outcomes are highly variable, likely due to differences in the availability of maternal NAD precursors vitamin B3 and tryptophan to the embryo and its extraembryonic tissues. Here, maternal plasma and yolk sac NAD metabolomes, embryonic NAD levels, and pregnancy outcomes were quantified in a CNDD mouse model to determine how maternal circulatory NAD precursor provision affects pregnancy outcome and to identify metabolic markers of CNDD risk. Maternal levels of nicotinamide positively correlated with embryonic NAD levels, highlighting its central role for embryonic NAD metabolism. Levels of nicotinamide‐derived excretion metabolites were the best predictors of adverse pregnancy outcome. NAD metabolomic analysis of pregnant women confirmed the relationship between dietary NAD precursor intake and circulatory nicotinamide and derived excretion product levels seen in mice, as women taking vitamin B3 supplements had elevated levels. Furthermore, mouse embryos with genetic disruption of NAD de novo synthesis ( Haao −/− ) were more susceptible to CNDD when maternal circulatory nicotinamide was limited, as their yolk sacs cannot generate NAD de novo from tryptophan. Metabolites originating from Haao −/− embryos were detectable in maternal plasma, showing that embryonic NAD metabolism also affects maternal circulation. Together, our findings elucidate the complex interplay between NAD metabolism of mother and conceptus and identify metabolic markers in maternal circulation that predict risk of NAD deficiency‐related adverse pregnancy outcomes.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 31 Oct 2025 04:31 |
| Last Modified: | 31 Oct 2025 04:31 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1706 |
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