title: Vitamin D Deficiency in BALB/c Mouse Pregnancy Increases Placental Transfer of Glucocorticoids.
abstract: 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 (2195 IU/kg) or deficient (0 IU/kg) diet for 5 weeks before and during pregnancy. Maternal serum, placentas and fetal brains were collected at embryonic day 14.5 or 17.5 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, 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. Furthermore, placental expression of the angiogenic factor vascular endothelial growth factor-A 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.
authors.affiliation: School of Anatomy, Physiology and Human Biology (D.T., J.E.H., C.S.W.), The University of Western Australia, Perth 6009, Australia; and School of Medicine (G.R.Z.), University of Tasmania, Hobart 7000, Australia.
authors.forename: Dijana
authors.initials: D
authors.lastname: Tesic
authors.affiliation: School of Anatomy, Physiology and Human Biology (D.T., J.E.H., C.S.W.), The University of Western Australia, Perth 6009, Australia; and School of Medicine (G.R.Z.), University of Tasmania, Hobart 7000, Australia.
authors.forename: Jazmin E
authors.initials: JE
authors.lastname: Hawes
authors.affiliation: School of Anatomy, Physiology and Human Biology (D.T., J.E.H., C.S.W.), The University of Western Australia, Perth 6009, Australia; and School of Medicine (G.R.Z.), 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 (D.T., J.E.H., C.S.W.), The University of Western Australia, Perth 6009, Australia; and School of Medicine (G.R.Z.), University of Tasmania, Hobart 7000, Australia.
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: Wyrwoll
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D007150:Immunohistochemistry; D008431:Maternal-Fetal Exchange; D008807:Mice, Inbred BALB C; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000097:blood / Q000503:physiopathology*
chemical_list: C498608:Dsip1 protein, mouse; D005938:Glucocorticoids; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003345:Corticosterone