title: Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse.
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 (2,195 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.
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia.
authors.forename: Jazmin E
authors.initials: JE
authors.lastname: Hawes
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia.
authors.forename: Dijana
authors.initials: D
authors.lastname: Tesic
authors.affiliation: Telethon Kids Institute, The University of Western Australia, Perth 6009, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Whitehouse
authors.affiliation: School of Medicine, University of Tasmania, Hobart 7000, Australia.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Zosky
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Smith
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia. Electronic address: caitlin.wyrwoll@uwa.edu.au.
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: Wyrwoll
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018568:Crown-Rump Length; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006257:Head / Q000196:embryology; D007150:Immunohistochemistry; D008297:Male; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012727:Sex Characteristics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D014446:Tyrosine 3-Monooxygenase
keywords: Foxp2; Neurodevelopment; Tyrosine hydroxylase; Vitamin D