PMID- 25753408 OWN - NLM STAT- MEDLINE DCOM- 20160104 LR - 20150408 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 286 DP - 2015 Jun 1 TI - Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse. PG - 192-200 LID - S0166-4328(15)00152-7 [pii] LID - 10.1016/j.bbr.2015.03.008 [doi] AB - 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-beta1 (Tgf-beta1) 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. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Hawes, Jazmin E AU - Hawes JE AD - School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia. FAU - Tesic, Dijana AU - Tesic D AD - School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia. FAU - Whitehouse, Andrew J AU - Whitehouse AJ AD - Telethon Kids Institute, The University of Western Australia, Perth 6009, Australia. FAU - Zosky, Graeme R AU - Zosky GR AD - School of Medicine, University of Tasmania, Hobart 7000, Australia. FAU - Smith, Jeremy T AU - Smith JT AD - School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia. FAU - Wyrwoll, Caitlin S AU - Wyrwoll CS AD - School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia. Electronic address: caitlin.wyrwoll@uwa.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150307 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp2 protein, mouse) RN - 0 (RNA, Messenger) RN - 0 (Repressor Proteins) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Transforming Growth Factor beta1) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Animals MH - Body Weight MH - Brain/*embryology/*metabolism/pathology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Crown-Rump Length MH - Disease Models, Animal MH - Dopaminergic Neurons/metabolism/pathology MH - Female MH - Forkhead Transcription Factors/metabolism MH - Head/embryology MH - Immunohistochemistry MH - Male MH - Mice, Inbred BALB C MH - Pregnancy MH - Pregnancy Complications/*metabolism MH - RNA, Messenger/metabolism MH - Repressor Proteins/metabolism MH - Sex Characteristics MH - Transforming Growth Factor beta1/metabolism MH - Tyrosine 3-Monooxygenase/metabolism MH - Vitamin D Deficiency/*metabolism OTO - NOTNLM OT - Foxp2 OT - Neurodevelopment OT - Tyrosine hydroxylase OT - Vitamin D EDAT- 2015/03/11 06:00 MHDA- 2016/01/05 06:00 CRDT- 2015/03/11 06:00 PHST- 2015/01/28 00:00 [received] PHST- 2015/03/02 00:00 [revised] PHST- 2015/03/02 00:00 [accepted] PHST- 2015/03/11 06:00 [entrez] PHST- 2015/03/11 06:00 [pubmed] PHST- 2016/01/05 06:00 [medline] AID - S0166-4328(15)00152-7 [pii] AID - 10.1016/j.bbr.2015.03.008 [doi] PST - ppublish SO - Behav Brain Res. 2015 Jun 1;286:192-200. doi: 10.1016/j.bbr.2015.03.008. Epub 2015 Mar 7.