Skip to main content Accessibility help
×
Home

Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey

  • J. K. Cleal (a1), P. E. Day (a1), C. L. Simner (a1), S. J. Barton (a2), P. A. Mahon (a2), H. M. Inskip (a2), K. M. Godfrey (a1) (a2) (a3), M. A. Hanson (a1) (a3), C. Cooper (a2) (a3) (a4), R. M. Lewis (a1), N. C. Harvey (a2) (a3) and the SWS Study Group (a2)...

Abstract

Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Women's Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey
      Available formats
      ×

Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

* Corresponding author: Dr J. K. Cleal, email jkc1@soton.ac.uk

References

Hide All
1 Harvey, NC, Javaid, MK, Poole, JR, et al. (2008) Paternal skeletal size predicts intrauterine bone mineral accrual. J Clin Endocrinol Metab 93, 16761681.
2 Javaid, MK, Crozier, SR, Harvey, NC, et al. (2006) Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet 367, 3643.
3 Holick, MF, Binkley, NC, Bischoff-Ferrari, HA, et al. (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96, 19111930.
4 Mahon, P, Harvey, N, Crozier, S, et al. (2010) Low maternal vitamin D status and fetal bone development: cohort study. J Bone Miner Res 25, 1419.
5 Crozier, SR, Harvey, NC, Inskip, HM, et al. (2012) Maternal vitamin D status in pregnancy is associated with adiposity in the offspring: findings from the Southampton Women's Survey. Am J Clin Nutr 96, 5763.
6 Harvey, NC, Moon, RJ, Sayer, AA, et al. (2014) Maternal antenatal vitamin D status and offspring muscle development: findings from the Southampton Women's Survey. J Clin Endocrinol Metab 99, 330337.
7 Lewis, RM, Cleal, JK, Ntani, G, et al. (2012) Relationship between placental expression of the imprinted PHLDA2 gene, intrauterine skeletal growth and childhood bone mass. Bone 50, 337342.
8 Martin, R, Harvey, NC, Crozier, SR, et al. (2007) Placental calcium transporter (PMCA3) gene expression predicts intrauterine bone mineral accrual. Bone 40, 12031208.
9 Cetin, I (2003) Placental transport of amino acids in normal and growth-restricted pregnancies. Eur J Obstet Gynecol Reprod Biol 110, S50S54.
10 Jansson, N, Pettersson, J, Haafiz, A, et al. (2006) Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 576, 935946.
11 Cleal, JK & Lewis, RM (2008) The mechanisms and regulation of placental amino acid transport to the human foetus. J Neuroendocrinol 20, 419426.
12 Day, PE, Cleal, JK, Lofthouse, EM, et al. (2013) Partitioning of glutamine synthesised by the isolated perfused human placenta between the maternal and fetal circulations. Placenta 34, 12231231.
13 Ericsson, A, Hamark, B, Jansson, N, et al. (2005) Hormonal regulation of glucose and system A amino acid transport in first trimester placental villous fragments. Am J Physiol Regul Integr Comp Physiol 288, R656R662.
14 Jansson, N, Greenwood, SL, Johansson, BR, et al. (2003) Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments. J Clin Endocrinol Metab 88, 12051211.
15 Shibata, E, Powers, RW, Rajakumar, A, et al. (2006) Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation. Am J Physiol Endocrinol Metab 291, E1009E1016.
16 Cleal, JK, Brownbill, P, Godfrey, KM, et al. (2007) Modification of fetal plasma amino acid composition by placental amino acid exchangers in vitro . J Physiol 582, 871882.
17 Lewis, RM, Glazier, J, Greenwood, SL, et al. (2007) l-Serine uptake by human placental microvillous membrane vesicles. Placenta 28, 445452.
18 Cleal, JK, Glazier, JD, Ntani, G, et al. (2011) Facilitated transporters mediate net efflux of amino acids to the fetus across the basal membrane of the placental syncytiotrophoblast. J Physiol 589, 987997.
19 MacDonald, PN, Haussler, CA, Terpening, CM, et al. (1991) Baculovirus-mediated expression of the human vitamin D receptor. Functional characterization, vitamin D response element interactions, and evidence for a receptor auxiliary factor. J Biol Chem 266, 1880818813.
20 Terpening, CM, Haussler, CA, Jurutka, PW, et al. (1991) The vitamin D-responsive element in the rat bone Gla protein gene is an imperfect direct repeat that cooperates with other cis-elements in 1,25-dihydroxyvitamin D3-mediated transcriptional activation. Mol Endocrinol 5, 373385.
21 Inskip, HM, Godfrey, KM, Robinson, SM, et al. (2006) Cohort profile: The Southampton Women's Survey. Int J Epidemiol 35, 4248.
22 Harrison, G, Buskirk, E, Carter, J, et al. (1988) Skinfold thicknesses and measurement technique. In Anthropometric Standardization Reference Manual, pp. 5570. Champaign, IL: Human Kinetics Books.
23 Cleal, JK, Day, P, Hanson, MA, et al. (2009) Measurement of housekeeping genes in human placenta. Placenta 30, 10021003.
24 Cleal, JK, Day, PL, Hanson, MA, et al. (2010) Sex differences in the mRNA levels of housekeeping genes in human placenta. Placenta 31, 556557.
25 Schulz, KF & Grimes, DA (2005) Multiplicity in randomised trials I: endpoints and treatments. Lancet 365, 15911595.
26 Wang, TT, Tavera-Mendoza, LE, Laperriere, D, et al. (2005) Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol 19, 26852695.
27 Yuan, W, Pan, W, Kong, J, et al. (2007) 1,25-Dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem 282, 2982129830.
28 Ogura, M, Taniura, H, Nakamichi, N, et al. (2007) Upregulation of the glutamine transporter through transactivation mediated by cAMP/protein kinase A signals toward exacerbation of vulnerability to oxidative stress in rat neocortical astrocytes. J Cell Physiol 212, 375385.
29 Karlic, H & Varga, F (2011) Impact of vitamin D metabolism on clinical epigenetics. Clin Epigenetics 2, 5561.
30 Vimaleswaran, KS, Berry, DJ, Lu, C, et al. (2013) Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med 10, e1001383.
31 Lewis, RM, Greenwood, SL, Cleal, JK, et al. (2010) Maternal muscle mass may influence system A activity in human placenta. Placenta 31, 418422.
32 Nykjaer, A, Dragun, D, Walther, D, et al. (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3 . Cell 96, 507515.
33 Brunton, JA, Weiler, HA & Atkinson, SA (1997) Improvement in the accuracy of dual-energy X-ray absorptiometry for whole body and regional analysis of body composition: validation using piglets and methodologic considerations in infants. Pediatr Res 41, 590596.

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed