The geometry of an organ’s vascular system determines the blood flow distribution to tissues for exchange of gas and nutrients by determining its vascular resistance. The importance of vascular geometry is evident in the placenta, where insufficient fetoplacental vascularity elevates vascular resistance thereby impairing perfusion, leading to one of the most common and severe pregnancy complications, intrauterine growth restriction (IUGR). The mouse is becoming a widely used model for human placental development due to the increasing availability of mouse models thought to have a placental defect. Vascular geometry can now be imaged and quantified using
micro-computed tomography (micro-CT) and results used to estimate resistance to blood flow. This thesis first describes the implementation of contrast agent perfusion and micro-CT imaging of the mouse fetoplacental vasculature throughout late gestation. Application of a vascular segmentation technique is then described and evaluated for quantification of the arterial
fetoplacental tree. Normal fetoplacental vascular development in late gestation is described for two common mouse strains, CD1 and C57Bl6 (B6). In B6 placentas, both late gestational capillary growth and thinning of the interhaemal membrane were blunted relative to CD1. Analysis of CD1 and B6 tree geometry revealed a constant number of arterial segments throughout late gestation in both strains but expansion of arterial diameters in B6 only, resulting in decreased B6 arterial resistance and shear stress in late gestation. Strain dependence shows
the importance of genetics in fetoplacental vascular development. Quantification of the arterial tree in a mouse model of maternal pre-pregnancy exposure to chemicals commonly found in cigarettes revealed an increase in vascular tortuousity and a reduced number of arteriole sized vessels. This led to an increase in vascular resistance and a predicted decrease in blood flow, which could contribute to the observed reduction in fetal weights. In future studies, the methods described herein can be used in phenotyping numerous mouse models which currently are suspected to have a placental vascular defect.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/31916 |
| Date | 11 January 2012 |
| Creators | Rennie, Monique Yvonne |
| Contributors | Sled, John G. |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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