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This Article Full Text Full Text (PDF) All Versions of this Article: 586/7/2015    most recent jphysiol.2007.149104v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bond, H. Articles by Glazier, J. D. Search for Related Content PubMed PubMed Citation Articles by Bond, H. Articles by Glazier, J. D. Related Collections Integrative

¹ Maternal and Fetal Health Research Group, School of Clinical and Laboratory Sciences, University of Manchester, St Mary's Hospital, Manchester, UK
² Paediatrics Centre, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary College, Homerton Hospital, London, UK

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 (^CaK_mf) and fetoplacental (^CaK_fp) directions; ^CaK_fp was < 5% of ^CaK_mf for all genotypes. At 18 dp, ^CaK_mf across perfused placenta and intact placenta (^CaK_mf(intact)) were similar and concordant with net calcium accretion rates in vivo. ^CaK_mf 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-D_9K 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-D_9K expression. In situ perfusion of mouse placenta is a robust methodology for allowing detailed dissection of placental transfer mechanisms in genetically modified mice.

(Received 29 November 2007; accepted after revision 1 February 2008; first published online 7 February 2008)
Corresponding author J. D. Glazier: Maternal and Fetal Heath Research Group, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK.  Email: j.glazier{at}manchester.ac.uk