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Since the advent of technologies to produce genetic knockout and transgenic mice, the number of mouse strains suggested to be useful as models for pregnancy-related complications in the human has risen substantially. Some of these share features in common with fetal growth restriction (FGR) and preeclampsia (PE) and could be useful for investigating aetiologies and for testing potential therapeutics to improve outcome in these diseases. However, since placental pathology is a major underlying factor in both FGR and PE, it is important to understand the similarities and differences in structure and function of the placenta between mice and women. The main aim of this review is to directly compare placental exchange physiology between human and mouse. The review will compare human and mouse in both normal and pathological circumstances, to attempt to answer the question of whether placental studies in the mouse can be translated to the human. The review includes descriptions of placental structure between the species, comparisons of nutrient transport, including amino acids, glucose and calcium, and evidence of how these transport systems are altered in both human FGR and mouse models of this disease. Finally, our review will conclude by examining studies in which mouse models of FGR/PE have been treated with drugs of potential therapeutic value in women and consider whether data obtained in mice can be a prelude for clinical trials in human., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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 (45)Ca across the placenta in maternofetal ((Ca)K(mf)) and fetoplacental ((Ca)K(fp)) directions; (Ca)K(fp) was < 5% of (Ca)K(mf) for all genotypes. At 18 dp, (Ca)K(mf) across perfused placenta and intact placenta ((Ca)K(mf(intact))) were similar and concordant with net calcium accretion rates in vivo. (Ca)K(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.