title: Expansion of the fetoplacental vasculature in late gestation is strain dependent in mice.
abstract: How the fetoplacental arterial tree grows and expands during late gestational development is largely unknown. In this study, we quantified changes in arterial branching in the fetal exchange region of the mouse placenta during late gestation, when capillarization increases rapidly. We studied two commonly used mouse strains, CD1 and C57Bl/6 (B6), at embryonic days (E)13.5, 15.5, and 17.5. B6 mice differ from CD1 mice by exhibiting a blunted fetal weight gain in late gestation. We found that B6 capillarization and interhemal membrane thinning were reduced and placental hypoxia-inducible factor-1α and VEGF-A expression were higher than CD1 near term. Automated vascular segmentation of microcomputed tomography data sets revealed that the number of arterial vessels ≥50 μm remained constant during late gestation in both strains, despite large increases in downstream capillary volume quantified by stereology (+65% in B6 mice and +200% in CD1 mice). Arterial diameters expanded in both strains from E13.5 to E15.5; however, diameters continued to expand to E17.5 in B6 mice only. The diameter scaling coefficient at branch sites was near optimal (-3.0) and remained constant in CD1 mice, whereas it decreased, becoming abnormal, in B6 mice at term (-3.5 ± 0.2). Based on arterial tree geometry, resistance remained constant throughout late gestation (∼0.45 mmHg·s·μl(-1)) in CD1 mice, whereas it decreased by 50% in late gestation in B6 mice. Quantification of the fetoplacental vasculature revealed significant strain-dependent differences in arterial and capillary expansion in late gestation. In both strains, enlargement of the fetoplacental arterial tree occurred primarily by increased arterial diameters with no change in segment numbers in late gestation.
authors.affiliation: Mouse Imaging Centre, Toronto Centre for Phenogenomics, Hospital for Sick Children, Canada.
authors.forename: Monique Y
authors.initials: MY
authors.lastname: Rennie
authors.forename: Jacqui
authors.initials: J
authors.lastname: Detmar
authors.forename: Kathie J
authors.initials: KJ
authors.lastname: Whiteley
authors.forename: Andrea
authors.initials: A
authors.lastname: Jurisicova
authors.forename: S Lee
authors.initials: SL
authors.lastname: Adamson
authors.forename: John G
authors.initials: JG
authors.lastname: Sled
mesh_terms: D000818:Animals; D001158:Arteries / Q000196:embryology; D015153:Blotting, Western; D002196:Capillaries / Q000000981:diagnostic imaging / Q000196:embryology* / Q000648:ultrastructure; D005260:Female; D020567:Fetal Weight; D005333:Fetus / Q000098:blood supply*; D005838:Genotype; D005865:Gestational Age; D006439:Hemodynamics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D008098:Litter Size; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000235:genetics; D010641:Phenotype; D010920:Placenta / Q000098:blood supply*; D021041:Placental Circulation; D011247:Pregnancy; D013045:Species Specificity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse