Search:
Computing and Library Services - delivering an inspiring information environment

Increased maternofetal calcium flux in parathyroid hormone-related protein-null mice

Bond, Helen, Dilworth, M.R., Baker, B., Cowley, E., Jimenez, A. Requena, Boyd, R.D.H., Husain, S.M., Ward, B.S., Sibley, Colin P. and Glazier, J.D. (2008) Increased maternofetal calcium flux in parathyroid hormone-related protein-null mice. The Journal of Physiology, 586 (7). pp. 2015-2025. ISSN 00223751

[img] PDF - Published Version
Restricted to Repository staff only

Download (526kB)

    Abstract

    The role of parathyroid hormone-related protein (PTHrP) in fetal calcium homeostasis and placental calcium transport was examined in mice homozygous for the deletion of the PTHrP gene (PTHrP−/− null; NL) compared to PTHrP+/+ (wild-type; WT) and PTHrP+/− (heterozygous; HZ) littermates. Fetal blood ionized calcium was significantly reduced in NL fetuses compared to WT and HZ groups at 18 days of pregnancy (dp) with abolition of the fetomaternal calcium gradient. In situ placental perfusion of the umbilical circulation at 18 dp was used to measure unidirectional clearance of 45Ca across the placenta in maternofetal (CaKmf) and fetoplacental (CaKfp) directions; CaKfp was < 5% of CaKmf for all genotypes. At 18 dp, CaKmf across perfused placenta and intact placenta (CaKmf(intact)) were similar and concordant with net calcium accretion rates in vivo. CaKmf was significantly raised in NL fetuses compared to WT and HZ littermates. Calcium accretion was significantly elevated in NL fetuses by 19 dp. Placental calbindin-D9K expression in NL fetuses was marginally enhanced (P < 0.07) but expression of TRPV6/ECaC2 and plasma membrane Ca2+-ATPase (PMCA) isoforms 1 and 4 were unaltered. We conclude that PTHrP is an important regulator of fetal calcium homeostasis with its predominant effect being on unidirectional maternofetal transfer, probably mediated by modifying placental calbindin-D9K expression. In situ perfusion of mouse placenta is a robust methodology for allowing detailed dissection of placental transfer mechanisms in genetically modified mice.

    Item Type: Article
    Subjects: Q Science > QH Natural history > QH301 Biology
    Schools: School of Applied Sciences
    Related URLs:
    Depositing User: Graham Stone
    Date Deposited: 01 Jul 2009 16:46
    Last Modified: 07 Sep 2011 09:11
    URI: http://eprints.hud.ac.uk/id/eprint/4906

    Document Downloads

    Downloader Countries

    More statistics for this item...

    Item control for Repository Staff only:

    View Item

    University of Huddersfield, Queensgate, Huddersfield, HD1 3DH Copyright and Disclaimer All rights reserved ©