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Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse.

Prenatal exposure to vitamin D is thought to be critical for optimal fetal neurodevelopment, yet vitamin D deficiency is apparent in a growing proportion of...

Authors:
Hawes JE, Tesic D, Whitehouse AJ, Zosky GR, Smith JT, Wyrwoll CS.

Authors notes:
Behav Brain Res. 2015;286:192-200.

Keywords:
Foxp2, Neurodevelopment, Tyrosine hydroxylase, Vitamin D

Abstract:
Prenatal exposure to vitamin D is thought to be critical for optimal fetal neurodevelopment, yet vitamin D deficiency is apparent in a growing proportion of pregnant women.

The aim of this study was to determine whether a mouse model of vitamin D-deficiency alters fetal neurodevelopment.

Female BALB/c mice were placed on either a vitamin D control (2195. IU/kg) or deficient (0. IU/kg) diet for 5 weeks prior to and during pregnancy.

Fetal brains were collected at embryonic day (E) 14.5 or E17.5 for morphological and gene expression analysis. Vitamin D deficiency during pregnancy reduced fetal crown-rump length and head size.

Moreover, lateral ventricle volume was reduced in vitamin D-deficient foetuses.

Expression of neurotrophin genes brain-derived neurotrophic factor (Bdnf) and transforming growth factor-β1 (Tgf-β1) was altered, with Bdnf reduced at E14.5 and increased at E17.5 following vitamin D deficiency.

Brain expression of forkhead box protein P2 (Foxp2), a gene known to be important in human speech and language, was also altered.

Importantly, Foxp2 immunoreactive cells in the developing cortex were reduced in vitamin D-deficient female foetuses.

At E17.5, brain tyrosine hydroxylase (TH) gene expression was reduced in females, as was TH protein localization (to identify dopamine neurons) in the substantia nigra of vitamin D-deficient female foetuses.

Overall, we show that prenatal vitamin D-deficiency leads to alterations in fetal mouse brain morphology and genes related to neuronal survival, speech and language development, and dopamine synthesis.

Vitamin D appears to play an important role in mouse neurodevelopment.