Research: Low maternal vitamin A intake increases the incidence of teratogen induced congenital diaphragmatic hernia in mice

Pediatr Res

. 2021 Mar 2. doi: 10.1038/s41390-021-01409-6. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/33654278/

Low maternal vitamin A intake increases the incidence of teratogen induced congenital diaphragmatic hernia in mice

Ayanna W Rocke 1 2Tianna G Clarke 1 2Timothy R A Dalmer 1 2Sydney A McCluskey 1Juan F Garcia Rivas 1Robin D Clugston 3 4Affiliations expand

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Abstract

Background: Congenital diaphragmatic hernia (CDH) is a severe birth defect associated with high perinatal mortality and long-term morbidity. The etiology of CDH is poorly understood although abnormal retinoid signaling has been proposed to contribute to abnormal diaphragm development. Existing epidemiological data suggest that inadequate dietary vitamin A intake is a risk factor for developing CDH.

Methods: Using a mouse model of teratogen-induced CDH, the objective of this study was to test the hypothesis that low maternal vitamin A intake contributes to abnormal diaphragm development. To test this hypothesis, we optimized a model of altered maternal dietary vitamin A intake and a teratogenic model of CDH in mice that recapitulates the hallmark features of posterolateral diaphragmatic hernia in humans.

Results: Our data uniquely show that low maternal dietary vitamin A intake and marginal vitamin A status increases the incidence of teratogen-induced CDH in mice.

Conclusion: Low dietary vitamin A intake and marginal vitamin A status lead to an increased incidence of teratogen-induced CDH in mice, highlighting the importance of adequate dietary vitamin A intake and CDH risk.

Impact: This study describes and validates a mouse model of altered maternal and fetal vitamin A status. This study links existing epidemiological data with a mouse model of teratogen-induced congenital diaphragmatic hernia, highlighting the importance of low maternal vitamin A intake as a risk factor for the development of congenital diaphragmatic hernia. This study supports the Retinoid Hypothesis, which posits that the etiology of congenital diaphragmatic hernia is linked to abnormal retinoid signaling in the developing diaphragm.

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