The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice.
We utilized a vitamin D receptor (VDR) gene knockout model to study the effects of maternal and fetal absence of VDR on maternal fertility, fetal-placental calcium transfer, and fetal mineral homoeostasis. Vdr null mice were profoundly hypocalcemic, conceived infrequently, and had significantly fewer viable fetuses in utero that were also of lower body weight. Supplementation of a calcium-enriched diet increased the rate of conception in Vdr nulls but did not normalize the number or weight of viable fetuses. Among offspring of heterozygous (Vdr(+/-)) mothers (wild type, Vdr(+/-), and Vdr null fetuses), there was no alteration in serum Ca, P, or Mg, parathyroid hormone, placental (45)Ca transfer, Ca and Mg content of the fetal skeleton, and morphology and gene expression in the fetal growth plates. Vdr null fetuses did have threefold increased 1,25-dihydroxyvitamin D levels accompanied by increased 1alpha-hydroxylase mRNA in kidney but not placenta; a small increase was also noted in placental expression of parathyroid hormone-related protein (PTHrP). Among offspring of Vdr null mothers, Vdr(+/-) and Vdr null fetuses had normal ionized calcium levels and a skeletal ash weight that was appropriate to the lower body weight. Thus our findings indicate that VDR is not required by fetal mice to regulate placental calcium transfer, circulating mineral levels, and skeletal mineralization. Absence of maternal VDR has global effects on fetal growth that were partly dependent on maternal calcium intake, but absence of maternal VDR did not specifically affect fetal mineral homeostasis.
Kovacs
Christopher S
CS
Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Dr., St. John's, Newfoundland and Labrador, Canada. ckovacs@mun.ca
Woodland
Mandy L
ML
Fudge
Neva J
NJ
Friel
James K
JK
D000818:Animals; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D002113:Calcification, Physiologic / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008903:Minerals / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D011270:Pregnancy, Animal / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*
D008903:Minerals; D018167:Receptors, Calcitriol; D002118:Calcium