Dietary calcium and phosphate restriction in guinea-pigs during pregnancy: fetal mineralization induces maternal hypocalcaemia despite increased 1 alpha,25-dihydroxycholecalciferol concentrations.
Guinea-pig fetuses at term are mineralized to a degree comparable with human fetuses, which makes the guinea-pig an attractive animal model to study maternal-fetal interactions with regard to Ca and phosphate (P) homeostasis. We studied non-pregnant and pregnant (day 57) vitamin D-replete guinea-pigs, fed either a normal guinea-pig chow with 9.6 g Ca/kg and 4.9 g P/kg or a study diet with 2 g Ca/kg and 1 g P/kg (low-Ca-P diet) for 7-8 weeks. Both pregnancy and the low-Ca-P diet decreased plasma concentrations of 25-hydroxycholecalciferol (25(OH)D3), but increased total and free 1 alpha,25-dihydroxycholecalciferol (1,25(OH)2D3), strongly suggesting an additive stimulation of 1 alpha-hydroxylase activity. Maternal and fetal 25(OH)D3 and 1,25(OH)2D3 levels were highly correlated (r 0.82 and 0.92 respectively, P < 0.001). Dual-energy absorption X-ray absorptiometry (DXA) showed that both pregnancy and the low-Ca-P diet decreased bone mineral density (BMD) of the maternal femur, particularly at the distal metaphysis. Despite higher 1,25(OH)2D3 concentrations and lower BMD, pregnant animals on the low-Ca-P diet were hypocalcaemic; blood Ca2+ levels were inversely correlated with the number of fetuses in this group (r -0.93, P < 0.001). Fetal growth as well as mineralization (assessed by whole-body and femoral DXA, bone histomorphometry and plasma-bone osteocalcin measurements) were unaltered in the low-Ca-P group. In conclusion, fetal mineralization proceeds normally but induces maternal hypocalcaemia in guinea-pigs with dietary restriction of Ca and P.
Rummens
K
K
Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, Belgium. katrien.rummens@uz.kuleuven.ac.be
Van Herck
E
E
van Bree
R
R
Bouillon
R
R
Van Assche
F A
FA
Verhaeghe
J
J
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000502:physiology; D002112:Calcifediol / Q000097:blood; D002113:Calcification, Physiologic / Q000502:physiology*; D002117:Calcitriol / Q000097:blood*; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D005269:Femur / Q000502:physiology; D005312:Fetal Blood / Q000737:chemistry; D006168:Guinea Pigs; D006996:Hypocalcemia / Q000209:etiology*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D023421:Models, Animal; D010710:Phosphates / Q000008:administration & dosage / Q000378:metabolism*; D011247:Pregnancy
D002136:Calcium, Dietary; D010710:Phosphates; D002117:Calcitriol; D002112:Calcifediol