The prevalence of vitamin D deficiency in pregnancy is increasing and implicated in adverse consequences for the health of offspring in later life. The aim of this study was to determine whether vitamin D deficiency increases fetal exposure to glucocorticoids, which are known to alter fetal development and result in adverse adult health outcomes. Female BALB/c mice were placed on either a vitamin D control (2,195 IU/kg) or deficient (0 IU/kg) diet for five weeks prior to and during pregnancy. Maternal serum, placentas and fetal brains were collected at embryonic day (E) 14.5 or E17.5 for morphological and gene expression analysis. Vitamin D deficiency during pregnancy increased maternal corticosterone concentrations and reduced placental weight. Maternal vitamin D deficiency decreased placental expression of 11β-hydroxysteroid dehydrogenase type II (11β-HSD2) which inactivates glucocorticoids thereby protecting the fetus from inappropriate glucocorticoid exposure. There was a corresponding increase in placental and fetal expression of the highly glucocorticoid sensitive factor glucocorticoid-induced leucine zipper (GILZ). Furthermore, placental expression of the angiogenic factor vascular endothelial growth factor-A (Vegfa) was reduced in vitamin D deficient pregnancies, with a corresponding decline in fetal capillary volume within the placenta. Overall, we show that prenatal vitamin D deficiency leads to an increase in maternal corticosterone, alterations in genes indicative of increased fetal glucocorticoid exposure and impairment in placental vascular development. Thus, the long-term adverse health consequences of vitamin D deficiency during early development may not just be due to alteration in direct vitamin D-related pathways but also altered fetal glucocorticoid exposure.

Item Type:	Refereed Article
Keywords:	vitamin D, development, placenta, glucocorticoids
Research Division:	Biomedical and Clinical Sciences
Research Group:	Reproductive medicine
Research Field:	Foetal development and medicine
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Zosky, GR (Professor Graeme Zosky)
ID Code:	102267
Year Published:	2015
Funding Support:	National Health and Medical Research Council (1042235)
Web of Science® Times Cited:	31
Deposited By:	Medicine
Deposited On:	2015-08-09
Last Modified:	2017-11-06
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