Poster Presentation 6th Australian Health and Medical Research Congress 2012

Effect of dietary calcium on vitamin D related genes in mouse kidney and placenta (#353)

Jessica A Laurence 1 2 , Paul H Anderson 3 , Tina Bianco-Miotto 1 2 , Claire T Roberts 1 2
  1. Robinson Institute, Adelaide, SA, Australia
  2. Department of Obstetrics & Gynaecology, The University of Adelaide, Adelaide, SA, Australia
  3. School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA, Australia

Gestational vitamin D (vitD) deficiency has been linked to pregnancy complications such as preeclampsia. While the primary source of circulating active 1,25-dihydroxyvitamin D (1,25D) occurs by the action of renal 25-hydroxyvitamin D 25-hydroxylase (CYP27B1) enzyme, the placenta has been shown to convert 25-hydroxyvitamin D (25D) to 1,25D by CYP27B1. Little is understood, however, regarding the contribution of placental 1,25D synthesis to function and whether it is impacted by vitD deficiency. To understand renal and placental vitD metabolism during pregnancy, expression of genes required for vitD metabolism and activity in both mouse kidney and placenta were examined. 3 week female C57BL6 mice were fed defined diets containing either 0 or 1000IU/kg vitD with either 0.1% (low) or 1% (high) calcium (Ca). At 12 weeks, mice (n=60) were mated, then killed at day 18.5 post-coitum and placenta and kidneys collected for gene expression of Cyp27b1, 25-hydroxyvitamin-D 24-hydroxylase (Cyp24a1) and vitamin D receptor (Vdr). Serum Ca levels were normal and unchanged between all groups. In low Ca fed mothers, renal Cyp27b1 mRNA levels were markedly higher, irrespective of dietary vitD, compared to high dietary calcium fed mice (P=0.003) and indicative of increased circulating 1,25D levels. Consistent with this, placental Cyp24a1 (P=0.001) and Vdr (P=0.035) were both increased suggesting that circulating 1,25D levels regulate these vitamin D responsive genes. While low dietary Ca did not increase placental Cyp27b1 mRNA levels, mice fed a vitD-deficient diet containing high dietary Ca resulted in markedly increased placental Cyp27b1 mRNA levels, suggesting that under conditions where circulating 25D and 1,25D levels are low, increased local synthesis of 1,25D in the placenta may compensate for impaired 1,25D supply. Further analysis of vitamin D responsive genes and placental morphology will establish the association between vitD activity and placental function.