Vitamin D deficiency during mouse development increases placental and fetal glucocorticoid exposure and alters fetal neural genes. — ASN Events
  1. Schedule
  2. Poster Session 1 - Neuroendocrinology of Stress I
  3. Vitamin D deficiency during mouse development increases placental and fetal glucocorticoid exposure and alters fetal neural genes.

Vitamin D deficiency during mouse development increases placental and fetal glucocorticoid exposure and alters fetal neural genes. (#245)

Jazmin Hawes 1 , Dijana Tesic 1 , Graeme Zosky 2 , Jeremy Smith 1 , Caitlin Wyrwoll 1
  1. The University of Western Australia, Nedlands, WA, Australia
  2. Telethon Kids, Perth, WA, Australia

Low levels of vitamin D during early life can alter brain development and increase the risk of later neuropsychiatric outcomes. The underlying mechanisms are unclear; one possiblity is alteration in fetal glucocorticoid exposure as inappropriate early exposure to glucocorticoids has implications for future mental health. Normally the fetus is protected from circulating glucocorticoids due to the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) which forms a barrier to glucocorticoids within the placenta. This experiment aimed to determine whether developmental vitamin D deficiency (DVD) was accompanied by alterations in placental and fetal glucocorticoid exposure and changes in fetal neural gene expression. Placentas and fetuses were obtained from vitamin D-replete (control) and –deficient BALB/c mice at E14.5 and E17.5. Quantitative RT-PCR was conducted in fetal brain and placental samples. Placental weight in DVD pregnancies was reduced at both E14.5 and E17.5 (P<0.01) and this was accompanied by a decrease in fetal weight at E17.5 (P<0.05) in DVD pregnancies in comparison to controls. The protective placental glucocorticoid barrier was dampened in DVD pregnancies, with placental 11β-HSD2 expression significantly decreased at E14.5 in comparison to control pregnancies (P<0.05). This downregulation of 11β-HSD2 presumably exposes the placenta and fetus to higher levels of glucocorticoids. Indeed, expression levels of glucocorticoid-induced leucine zipper (GILZ; which is upregulated by glucocorticoids binding to the glucocorticoid receptor) at E14.5 were increased in both placentas and fetal brains from DVD pregnancies in comparison to controls (P<0.05). Accompanying this were changes in fetal neural FOXP2 and tyrosine hydroxylase, with both decreased in DVD fetal brains in comparison to controls (P<0.05). This work reveals that DVD is accompanied by increased exposure of fetal and placental tissues to glucocorticoids. This raises the possibility that fetal neurodevelopmental changes consequent of DVD may be driven by inappropriate exposure to glucocorticoids.