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Maternal 25(OH)-vitamin D status in late pregnancy and mRNA expression of placental calcium transporter predict intrauterine bone mineral accrual in the offspring

Maternal 25(OH)-vitamin D status in late pregnancy and mRNA expression of placental calcium transporter predict intrauterine bone mineral accrual in the offspring
Maternal 25(OH)-vitamin D status in late pregnancy and mRNA expression of placental calcium transporter predict intrauterine bone mineral accrual in the offspring
Aims: Evidence suggests that intrauterine bone mineral accrual predicts osteoporosis risk in later life, and that maternal 25(OH)-vitamin D status in pregnancy is a determinant of neonatal bone mass. We aimed to explore the relationship between intrauterine bone mineral accrual in the offspring, and 1) maternal 25(OH)-vitamin D status during late pregnancy, and 2) expression of
calcium transporters in the placenta.

Methods: Pregnancies were recruited from the Southampton Women’s Survey, a unique, ongoing, well established cohort of women, aged 20–34 years, assessed before and during pregnancy. Maternal 25(OH)-vitamin D status was measured by radioimmunoassay in late pregnancy (34 weeks); the healthy, term, neonates underwent whole body (WB) DXA within 20 days of birth, using a Lunar DPX instrument. Placental samples, snap frozen in liquid nitrogen within 30 minutes of birth, were available for 70 of the pregnancies. A quantitative real time polymerase chain reaction was used to measure the mRNA expression of PMCA isoforms 1, 3 and 4 in the placenta, using beta-actin as a control gene.

Results: 556 (286 males) neonates were studied. Offspring of mothers who were deficient (<33nmol/l) in 25(OH)-vitamin D in late pregnancy had lower bone mass than those of replete mothers. Thus the mean WB bone area (BA) of the female offspring of 25(OH)-vitamin D deficient mothers was 110cm2 vs 119cm2 in offspring of replete mothers (p=0.04). The mean WB bone mineral content (BMC) for offspring of deficient vs replete mothers was 58g vs 63g (p=0.04), respectively. The relationships in the boys did not reach statistical significance. There was no association with maternal alkaline phosphatase. After controlling for beta-actin expression, PMCA3 mRNA expression predicted neonatal WB BA (r=0.28,p=0.02), WB BMC (r=0.25,p=0.04), placental weight (r=0.26,p=0.03), and birth weight (r=0.33,p=0.006).

Conclusions: These data are consistent with previous findings that mothers deficient in 25(OH)-vitamin D in pregnancy have children with reduced bone mass. The mechanism underlying this process may be explained, in part, by the demonstrated association between expression of the placental calcium transporter PMCA3 and neonatal whole body bone mineral content. Further elucidation of this process may allow development of novel therapeutic strategies to optimise childhood bone mineral accrual and thus reduce osteoporotic fractures in future generations.
bone, calcium, pregnancy, expression, maternal
0937-941X
S9 (OC9)
Harvey, N.C.
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Martin, R.
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Javaid, M.K
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Swaminathan, R.
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Taylor, P.
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Poole, J.R.
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Arden, N.K
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Dennison, E.M.
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Inskip, H.M.
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Godfrey, K.
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Lewis, R.M.
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Cooper, C.
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Harvey, N.C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Martin, R.
b8a7a9c2-d335-436d-8f57-ef96bb338c84
Javaid, M.K
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Swaminathan, R.
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Taylor, P.
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Poole, J.R.
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Arden, N.K
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Dennison, E.M.
ee647287-edb4-4392-8361-e59fd505b1d1
Inskip, H.M.
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Godfrey, K.
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Lewis, R.M.
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Cooper, C.
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Harvey, N.C., Martin, R., Javaid, M.K, Swaminathan, R., Taylor, P., Poole, J.R., Arden, N.K, Dennison, E.M., Inskip, H.M., Godfrey, K., Lewis, R.M. and Cooper, C. (2006) Maternal 25(OH)-vitamin D status in late pregnancy and mRNA expression of placental calcium transporter predict intrauterine bone mineral accrual in the offspring. Osteoporosis International, 17 (Supplement 2), S9 (OC9). (doi:10.1007/s00198-006-0096-z).

Record type: Article

Abstract

Aims: Evidence suggests that intrauterine bone mineral accrual predicts osteoporosis risk in later life, and that maternal 25(OH)-vitamin D status in pregnancy is a determinant of neonatal bone mass. We aimed to explore the relationship between intrauterine bone mineral accrual in the offspring, and 1) maternal 25(OH)-vitamin D status during late pregnancy, and 2) expression of
calcium transporters in the placenta.

Methods: Pregnancies were recruited from the Southampton Women’s Survey, a unique, ongoing, well established cohort of women, aged 20–34 years, assessed before and during pregnancy. Maternal 25(OH)-vitamin D status was measured by radioimmunoassay in late pregnancy (34 weeks); the healthy, term, neonates underwent whole body (WB) DXA within 20 days of birth, using a Lunar DPX instrument. Placental samples, snap frozen in liquid nitrogen within 30 minutes of birth, were available for 70 of the pregnancies. A quantitative real time polymerase chain reaction was used to measure the mRNA expression of PMCA isoforms 1, 3 and 4 in the placenta, using beta-actin as a control gene.

Results: 556 (286 males) neonates were studied. Offspring of mothers who were deficient (<33nmol/l) in 25(OH)-vitamin D in late pregnancy had lower bone mass than those of replete mothers. Thus the mean WB bone area (BA) of the female offspring of 25(OH)-vitamin D deficient mothers was 110cm2 vs 119cm2 in offspring of replete mothers (p=0.04). The mean WB bone mineral content (BMC) for offspring of deficient vs replete mothers was 58g vs 63g (p=0.04), respectively. The relationships in the boys did not reach statistical significance. There was no association with maternal alkaline phosphatase. After controlling for beta-actin expression, PMCA3 mRNA expression predicted neonatal WB BA (r=0.28,p=0.02), WB BMC (r=0.25,p=0.04), placental weight (r=0.26,p=0.03), and birth weight (r=0.33,p=0.006).

Conclusions: These data are consistent with previous findings that mothers deficient in 25(OH)-vitamin D in pregnancy have children with reduced bone mass. The mechanism underlying this process may be explained, in part, by the demonstrated association between expression of the placental calcium transporter PMCA3 and neonatal whole body bone mineral content. Further elucidation of this process may allow development of novel therapeutic strategies to optimise childhood bone mineral accrual and thus reduce osteoporotic fractures in future generations.

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More information

Published date: May 2006
Additional Information: Oral Communication Abstracts: S133
Keywords: bone, calcium, pregnancy, expression, maternal

Identifiers

Local EPrints ID: 61200
URI: http://eprints.soton.ac.uk/id/eprint/61200
ISSN: 0937-941X
PURE UUID: 8ae9f34c-d136-4d93-8c8e-c3f4572827b5
ORCID for N.C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for E.M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for H.M. Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for K. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for R.M. Lewis: ORCID iD orcid.org/0000-0003-4044-9104
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 18 Nov 2008
Last modified: 18 Mar 2024 02:58

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Contributors

Author: N.C. Harvey ORCID iD
Author: R. Martin
Author: M.K Javaid
Author: R. Swaminathan
Author: P. Taylor
Author: J.R. Poole
Author: N.K Arden
Author: E.M. Dennison ORCID iD
Author: H.M. Inskip ORCID iD
Author: K. Godfrey ORCID iD
Author: R.M. Lewis ORCID iD
Author: C. Cooper ORCID iD

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