title: Vessel tortuousity and reduced vascularization in the fetoplacental arterial tree after maternal exposure to polycyclic aromatic hydrocarbons.
abstract: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and the main toxicants found in cigarettes. Women are often exposed to PAHs before pregnancy, typically via prepregnancy smoking. To determine how prepregnancy exposure affects the fetoplacental vasculature of the placenta, we exposed female mice to PAHs before conception, perfused the fetoplacental arterial trees with X-ray contrast agent, and imaged the vasculature ex vivo by microcomputed tomography (micro-CT) at embryonic day 15.5. Automated vascular segmentation and flow calculations revealed that in control trees, <40 chorionic plate vessels (diameter>180 μm) gave rise to ∼1,300 intraplacental arteries (50-180 μm), predicting an arterial vascular resistance of 0.37±0.04 mmHg·s·μl(-1). PAH exposure increased vessel curvature of chorionic plate vessels and significantly increased the tortuousity ratio of the tree. Intraplacental arteries were reduced by 17%, primarily due to a 27% decrease in the number of arteriole-sized (50-100 μm) vessels. There were no changes in the number of chorionic vessels, the depth or span of the tree, the diameter scaling coefficient, or the segment length-to-diameter ratio. PAH exposure resulted in a tree with a similar size and dichotomous branching structure, but one that was comparatively sparse so that arterial vascular resistance was increased by 30%. Assuming the same pressure gradient, blood flow would be 19% lower. Low flow may contribute to the 23% reduction observed in fetal weight. New insights into the specific effects of PAH exposure on a developing arterial tree were achieved using micro-CT imaging and automated vascular segmentation analysis.
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, and Department of Medical Biophysics, Institute of Medical Studies, University of Toronto, 25 Orde St., Toronto, ON, Canada M5T 3H7.
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: Jian
authors.initials: J
authors.lastname: Yang
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 / Q000187:drug effects* / Q000473:pathology; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002823:Chorion / Q000098:blood supply; D003287:Contrast Media; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D008953:Models, Anatomic; D009389:Neovascularization, Pathologic; D010641:Phenotype; D010920:Placenta / Q000187:drug effects; D021041:Placental Circulation / Q000187:drug effects*; D010929:Placentation; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012907:Smoking / Q000473:pathology; D014057:Tomography, X-Ray Computed; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D003287:Contrast Media; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon