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Dietary calcium and phosphate restriction in guinea-pigs during pregnancy: fetal mineralization induces maternal hypocalcaemia despite increased 1α,25-dihydroxycholecalciferol concentrations

Published online by Cambridge University Press:  09 March 2007

Katrien Rummens ,
Erik Van Herck ,
Rita van Bree ,
Roger Bouillon ,
F. André Van Assche  and
Johan Verhaeghe
Katrien Rummens*
Affiliation:
Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Erik Van Herck
Affiliation:
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Rita van Bree
Affiliation:
Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Roger Bouillon
Affiliation:
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
F. André Van Assche
Affiliation:
Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Johan Verhaeghe
Affiliation:
Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
*
*Corresponding author: Dr Katrien Rummens, fax +32 16 344205, email katrien.rummens@uz.kuleuven.ac.be
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Abstract

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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 1α,25-dihydroxycholecalciferol (1,25(OH)2D3), strongly suggesting an additive stimulation of 1α-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.

Keywords

PregnancyDietary calcium restrictionGuinea-pig
Type
Research Article
Information
British Journal of Nutrition , Volume 84 , Issue 4 , October 2000 , pp. 495 - 504
Copyright
Copyright © The Nutrition Society 2000

References

Bodansky, M and Duff, VB (1941) Dependence of fetal growth and storage of calcium and phosphorus on the parathyroid function and diet of pregnant rats. Journal of Nutrition 22, 25–41.CrossRefGoogle Scholar
Bolt, MJG, Jensen, WE and Sitrin, MD (1992) Metabolism of 25-hydroxyvitamin D3 in rats: low-calcium diet. vs. calcitriol infusion. American Journal of Physiology 262, E359–E367.Google ScholarPubMed
Bouillon, R, Van Assche, FA, Van Baelen, H, Heyns, W and De Moor, P (1981) Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. Journal of Clinical Investigation 67, 589–596.CrossRefGoogle ScholarPubMed
Bouillon, R, Van Herck, E, Jans, I, Tan, BK, Van Baelen, H and De Moor, P (1984) Two direct (nonchromatographic) assays for 25-hydroxyvitamin D. Clinical Chemistry 30, 1731–1736.CrossRefGoogle ScholarPubMed
Bronner, F (1992) Current concepts of calcium absorption: an overview. Journal of Nutrition 122, 641–643.CrossRefGoogle ScholarPubMed
Chiang, M, Russell, SM and Nicoll, CS (1990) Growth-promoting properties of the internal milieu of pregnant and lactating rats. American Journal of Physiology 258, E98–E102.Google ScholarPubMed
Cross, NA, Hillman, LS, Allen, SH, Krause, GF and Vieira, NE (1995) Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study. American Journal of Clinical Nutrition 61, 514–523.CrossRefGoogle ScholarPubMed
Engle, WA and Lemons, JA (1986) Composition of the fetal and maternal guinea pig throughout gestation. Pediatric Research 20, 1156–1160.CrossRefGoogle ScholarPubMed
Fenton, E and Britton, HG (1980) 25-Hydroxycholecalciferol 1α-hydroxylase activity in the kidney of the fetal, neonatal and adult guinea pig. Biology of the Neonate 37, 254–256.CrossRefGoogle Scholar
Fox, J, Bunker, JE, Kamimura, M and Wong, PF (1990) Low-calcium diets increase both production and clearance of 1,25-dihydroxyvitamin D3 in rats. American Journal of Physiology 258, E282–E287.Google ScholarPubMed
Instiute of Medicine (1998) Dietary Reference Intakes. Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press.Google Scholar
Iob, V and Swanson, WW (1934) Mineral growth of the human fetus. American Journal of Diseases in Childhood 47, 302–306.Google Scholar
Jones, G, Couper, D, Riley, M, Goff, C and Dwyer, T (1997) Determinants of bone mass in prepubertal children: antenatal, neonatal and current influences. Journal of Bone and Mineral Research 12 (Suppl. 1), S145.Google Scholar
Knox, G and Morley, D (1960) Twinning in Yoruba women. Journal of Obstetrics and Gynaecology of the British Empire 67, 981–984.CrossRefGoogle ScholarPubMed
Lees, CJ and Jerome, CP (1998) Effects of pregnancy and lactation on bone in cynomolgus macaques: histomorphometric analysis of iliac biopsies. Bone 22, 545–549.CrossRefGoogle Scholar
Marie, PJ, Cancela, L, Le Boulch, N and Miravet, L (1986) Bone changes due to pregnancy and lactation: influence of vitamin D status. American Journal of Physiology 251, E400–E406.Google ScholarPubMed
Oginni, LM, Worsfold, M, Oyelami, OA, Sharp, CA, Powell, DE and Davie, MWJ (1996) Etiology of rickets in Nigerian children. Journal of Pediatrics 128, 692–694.CrossRefGoogle ScholarPubMed
Ott, SM, Lipkin, EW and Newell-Morris, L (1999) Bone physiology during pregnancy and lactation in young macaques. Journal of Bone and Mineral Research 14, 1779–1788.CrossRefGoogle ScholarPubMed
Parfitt, AM, Drezner, MK, Glorieux, FH, Kanis, JA, Malluche, H, Meunier, PJ, Ott, SM and Recker, RR (1987) Bone histomorphometry: standardization of nomenclature, symbols and units. Journal of Bone and Mineral Research 6, 595–610.CrossRefGoogle Scholar
Paulson, SK, Ford, KK and Langman, CB (1990) Pregnancy does not alter the metabolic clearance of 1,25-dihydroxyvitamin D in rats. American Journal of Physiology 258, E158–E162.Google Scholar
Prentice, A, Laskey, MA, Shaw, J, Hudson, GJ, Day, KC, Jarjou, LMA, Dibba, B and Paul, AA (1993) The calcium and phosphorus intakes of rural Gambian women during pregnancy and lactation. British Journal of Nutrition 69, 885–896.CrossRefGoogle ScholarPubMed
Ritchie, LD, Fung, EB, Halloran, BP, Turnlund, JR, Van Loan, MD, Cann, CE and King, JC (1998) A longitudinal study of calcium homeostasis during human pregnancy and lactation and after resumption of menses. American Journal of Clinical Nutrition 67, 693–701.CrossRefGoogle ScholarPubMed
Ron, M, Levitz, M, Chuba, J and Dancis, J (1984) Transfer of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 across the perfused human placenta. American Journal of Obstetrics and Gynecology 148, 370–374.CrossRefGoogle ScholarPubMed
Symonds, HW, Bubar, RH, Crackel, W and Twardock, AR (1978) The effect of litter size on placental blood flow and placental calcium transfer in the multifoetate guinea-pig. British Journal of Nutrition 39, 347–356.CrossRefGoogle ScholarPubMed
Tojo, Y, Kurabayashi, T, Honda, A, Yamamoto, Y, Yahata, T, Takakuwa, K and Tanaka, K (1998) Bone structural and metabolic changes at the end of pregnancy and lactation in rats. American Journal of Obstetrics and Gynecology 178, 180–185.CrossRefGoogle ScholarPubMed
Twardock, AR (1967) Placental transfer of calcium and strontium in the guinea pig. American Journal of Physiology 213, 837–842.CrossRefGoogle ScholarPubMed
Vanderschueren, D, Van Herck, E, Suiker, AMH, Allewaert, K, Visser, WJ, Geusens, P and Bouillon, R (1992) Bone and mineral metabolism in the adult guinea pig: long-term effects of estrogen and androgen deficiency. Journal of Bone and Mineral Research 7, 1407–1415.CrossRefGoogle ScholarPubMed
Verhaeghe, J, Allewaert, K, Van Herck, E, Van Bree, R, Van Assche, FA and Bouillon, R (1994) 1,25-Dihydroxyvitamin D3 and osteocalcin in maternal and fetal guinea pigs. Bone and Mineral 26, 261–273.CrossRefGoogle ScholarPubMed
Verhaeghe, J and Bouillon, R (1992) Calciotropic hormones during reproduction. Journal of Steroid Biochemistry and Molecular Biology 41, 469–477.CrossRefGoogle ScholarPubMed
Verhaeghe, J, Bouillon, R, Lissens, W, Visser, WJ and Van Assche, FA (1988) Diabetic and low Ca–P diets have opposite effects on adult and fetal bone and mineral metabolism. American Journal of Physiology 254, E496–E504.Google Scholar
Verhaeghe, J, Oloumi, G, Van Herck, E, van Bree, R, Dequeker, J, Einhorn, TA and Bouillon, R (1997) Effects of long-term diabetes and/or high-dose 17β-estradiol on bone formation, bone mineral density, and strength in ovariectomized rats. Bone 20, 421–428.CrossRefGoogle ScholarPubMed
Verhaeghe, J, Thomasset, M, Bréhier A, Van Assche, FA and Bouillon, R (1988) 1,25(OH)2D3 and Ca-binding protein in fetal rats: relationship to the maternal vitamin D status. American Journal of Physiology 254, E505–E512.Google Scholar
Verhaeghe, J, Thomasset, M, Van Assche, FA and Bouillon, R (1990) Osteocalcin is vitamin D-dependent during the perinatal period in the rat. Journal of Developmental Physiology 14, 311–317.Google ScholarPubMed
Verhaeghe, J, Van Herck, E and Bouillon, R (1995) Umbilical cord osteocalcin in normal pregnancies and pregnancies complicated by fetal growth retardation or diabetes mellitus. Biology of the Neonate 68, 377–383.CrossRefGoogle ScholarPubMed
Verhaeghe, J, Van Herck, E, van Bree, R, Moermans, K and Bouillon, R (1997) Decreased osteoblast activity in spontaneously diabetic rats. In vivo studies on the pathogenesis. Endocrine 7, 165–175.CrossRefGoogle ScholarPubMed
Verhaeghe, J, Van Herck, E, Van Bree, R, Van Assche, FA and Bouillon, R (1989) Osteocalcin during the reproductive cycle in normal and diabetic rats. Journal of Endocrinology 120, 143–151.CrossRefGoogle ScholarPubMed
Walling, MW (1977) Intestinal Ca and phosphate transport: differential responses to vitamin D3 metabolites. American Journal of Physiology 233, E488–E494.Google ScholarPubMed
Widdowson, EM (1950) Chemical composition of newly born mammals. Nature 166, 626–628.CrossRefGoogle ScholarPubMed