Hostname: page-component-7c8c6479df-xxrs7 Total loading time: 0 Render date: 2024-03-17T06:02:31.768Z Has data issue: false hasContentIssue false

Effect of vitamin D deficiency during pregnancy on offspring bone structure, composition and quality in later life

Published online by Cambridge University Press:  26 July 2012

S. A. Lanham*
Affiliation:
Bone and Joint Research Group, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton, UK
C. Roberts
Affiliation:
Bone and Joint Research Group, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton, UK
A. K. Habgood
Affiliation:
Bone and Joint Research Group, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton, UK
S. Alexander
Affiliation:
Queensland Centre for Mental Health Research, Queensland Brain Institute, University of Queensland, St Lucia, Australia
T. H. J. Burne
Affiliation:
Queensland Centre for Mental Health Research, Queensland Brain Institute, University of Queensland, St Lucia, Australia
D. W. Eyles
Affiliation:
Queensland Centre for Mental Health Research, Queensland Brain Institute, University of Queensland, St Lucia, Australia
C. N. Trueman
Affiliation:
School of Ocean and Earth Science, University of Southampton Waterfront Campus, Southampton, UK
M. Cooper
Affiliation:
School of Ocean and Earth Science, University of Southampton Waterfront Campus, Southampton, UK
J. J. McGrath
Affiliation:
Queensland Centre for Mental Health Research, Queensland Brain Institute, University of Queensland, St Lucia, Australia
R. O. C. Oreffo*
Affiliation:
Bone and Joint Research Group, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton, UK
*
*Address for correspondence: S. Lanham or R. Oreffo, Bone and Joint Research Group, MP887, Institute of Developmental Sciences, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. (Email S.A.Lanham@soton.ac.uk or roco@soton.ac.uk)
*Address for correspondence: S. Lanham or R. Oreffo, Bone and Joint Research Group, MP887, Institute of Developmental Sciences, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. (Email S.A.Lanham@soton.ac.uk or roco@soton.ac.uk)

Abstract

During foetal development, calcium requirements are met as a consequence of maternal adaptations independent of vitamin D status. In contrast, after birth, dependency on vitamin D appears necessary for calcium metabolism and skeletal health. We used a rodent model (Sprague-Dawley rats), to determine if maternal vitamin D deficiency during pregnancy had a deleterious effect on bone structure at birth. Vitamin D deplete females were maintained under deplete conditions until birth of the pups, whereupon all dams were fed a vitamin D replete diet. Offspring were harvested at birth, and 140 days of age. Bones were analyzed using micro-computed tomography and strength tested to study differences in bone structure, density and strength and subjected to elemental analysis using plasma mass spectrometry to determine strontium, barium and calcium contents. Offspring from deplete mothers displayed altered trabecular parameters in the femur at birth and 140 days of age. In addition, at 140 days of age there was evidence of premature mineralization of the secondary ossification centre of the femoral head. Elemental analysis showed increased strontium uptake in the femur of the developmentally vitamin D-deficient offspring. Vitamin D depletion during development in the offspring may have a long-lasting effect, despite repletion of vitamin D from birth. This may have consequences for human health given the low vitamin D levels seen during pregnancy and current lifestyle of sun avoidance due to the risk of skin cancer.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Ralston, SH. Do genetic markers aid in risk assessment? Osteoporos Int. 1998; 8(Suppl. 1), S37S42.Google Scholar
2.Cooper, C, Cawley, M, Bhalla, A, et al. Childhood growth, physical activity, and peak bone mass in women. J Bone Miner Res. 1995; 10, 940947.Google Scholar
3.Cooper, C, Fall, C, Egger, P, et al. Growth in infancy and bone mass in later life. Ann Rheum Dis. 1997; 56, 1721.CrossRefGoogle ScholarPubMed
4.Cooper, C, Javaid, MK, Taylor, P, et al. The fetal origins of osteoporotic fracture. Calcif Tissue Int. 2002; 70, 391394.Google Scholar
5.Fall, C, Hindmarsh, P, Dennison, EM, et al. Programming of growth hormone secretion and bone mineral density in elderly men: a hypothesis. J Clin Endocrinol Metab. 1998; 83, 135139.Google Scholar
6.Godfrey, KM, Barker, DJP. Fetal nutrition and adult disease. Am J Clin Nutr. 2000; 71(Suppl 5), 1344S1352S.Google Scholar
7.Barker, DJP. The fetal origins of diseases of old age. Eur J Clin Nutr. 1992; 46(Suppl. 3), S3S9.Google Scholar
8.Kovacs, CS. Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. Am J Clin Nutr. 2008; 88(Suppl), 520S552S.CrossRefGoogle ScholarPubMed
9.Miller, S, Halloran, B, DeLuca, H, Jee, W. Studies on the role of vitamin D in early skeletal development, mineralization, and growth in rats. Calcif Tissue Int. 1983; 35, 455460.CrossRefGoogle ScholarPubMed
10.Li, YC, Amling, M, Pirro, AE, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology. 1998; 139, 43914396.Google Scholar
11.Javaid, MK, Crozier, SR, Harvey, NC, et al. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet. 2006; 367, 3643.Google Scholar
12.Rummens, K, van Bree, RE, Van Herck, E, et al. Vitamin D deficiency in guinea pigs: exacerbation of bone phenotype during pregnancy and disturbed fetal mineralization, with recovery by 1,25(OH)(2)D-3 infusion or dietary calcium-phosphate supplementation. Calcif Tissue Int. 2002; 71, 364375.Google Scholar
13.McGrath, JJ, Barnett, AG, Eyles, DW. The association between birth weight, season of birth and latitude. Ann Hum Biol. 2005; 32, 547559.Google Scholar
14.Namgung, R, Tsang, RC, Lee, C, et al. Low total body bone mineral content and high bone resorption in Korean winter-born versus summer-born newborn infants. J Pediatr. 1998; 132, 421425.Google Scholar
15.Eyles, DW, Brown, J, kay-Sim, A, McGrath, JJ, Feron, F. Vitamin D3 and brain development. Neuroscience. 2003; 118, 641653.Google Scholar
16.Burne, THJ, O'Loan, J, Splatt, K, et al. Developmental vitamin D (DVD) deficiency alters pup-retrieval but not isolation-induced pup ultrasonic vocalizations in the rat. Physiol Behav. 2011; 102, 201204.Google Scholar
17.Horton, JA, Bariteau, JT, Loomis, RM, Strauss, JA, Damron, TA. Ontogeny of skeletal maturation in the juvenile rat. Anat Rec. 2008; 291, 283292.Google Scholar
18.Lanham, SA, Bertram, C, Cooper, C, Oreffo, RO. Animal models of maternal nutrition and altered offspring bone structure – bone development across the lifecourse. Eur Cell Mater. 2011; 22, 321332.Google Scholar
19.O'Loan, J, Eyles, DW, Kesby, J, et al. Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology. 2007; 32, 227234.Google Scholar
20.Clements, MR, Fraser, DR. Vitamin-D supply to the rat fetus and neonate. J Clin Invest. 1988; 81, 17681773.Google Scholar
21.Morris, HA, Anderson, PH. Autocrine and paracrine actions of vitamin D. Clin Biochem Rev. 2010; 31, 129138.Google Scholar
22.Gombart, AF, Borregaard, N, Koeffler, HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005; 19, 10671077.Google Scholar
23.Thoma-Uszynski, S, Stenger, S, Takeuchi, O, et al. Induction of direct antimicrobial activity through mammalian toll-like receptors. Science. 2001; 291, 15441547.Google Scholar
24.Kovacs, CS, Woodland, ML, Fudge, NJ, Friel, JK. The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice. Am J Physiol Endocrinol Metab. 2005; 289, E133E144.CrossRefGoogle ScholarPubMed
25.Finch, SL, Rauch, F, Weiler, HA. Postnatal vitamin D supplementation following maternal dietary vitamin D deficiency does not affect bone mass in weanling guinea pigs. J Nutr. 2010; 140, 15741581.Google Scholar
26.Dawodu, A, Wagner, CL. Mother–child vitamin D deficiency: an international perspective. Arch Dis Child. 2007; 92, 737740.Google Scholar
27.Morley, R, Carlin, JB, Pasco, JA, Wark, JD. Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J Clin Endocrinol Metab. 2006; 91, 906912.Google Scholar
28.Mahon, P, Harvey, N, Crozier, S, et al. Low maternal vitamin D status and fetal bone development: cohort study. J Bone Miner Res. 2010; 25, 1419.Google Scholar
29.Williams, AF. Vitamin D in pregnancy: an old problem still to be solved? Arch Dis Child. 2007; 92, 740741.Google Scholar