Investigating the Upstream and Downstream Hemodynamic Boundary Conditions of Healthy and Growth-Restricted Rat Feto-Placental Arterial Networks.

The placenta uniquely develops to orchestrate maternal adaptations and support fetal growth and development. The expansion of the feto-placental vascular network, in part, underpins function. However it is unclear how vascular development is synergistically influenced by hemodynamics and how impairment may lead to fetal growth restriction (FGR). Here, we present a robust framework consisting of ex vivo placental casting, imaging and computational fluid dynamics of rat feto-placental networks where we investigate inlet (steady and transient) and outlet (zero-pressure, Murray's Law, asymmetric fractal trees and porous blocks) boundary conditions in a model of growth-restriction. We show that the Murray's Law flow-split boundary condition is not always appropriate and that mean steady-state inlet conditions produce comparable results to transient flow. However, we conclude that transient simulations should be adopted as they provide a larger amount of valuable data, a necessity to bridge the current knowledge gap in placental biomechanics. We also show preliminary data on changes in flow, shear stress, and flow deceleration between control and growth-restricted feto-placental networks. Our proposed framework provides a standardized approach for structural and hemodynamic analysis of feto-placental vasculature and has the potential to enhance our understanding of placental function.

Advances in imaging feto-placental vasculature: new tools to elucidate the early life origins of health and disease.

Optimal placental function is critical for fetal development, and therefore a crucial consideration for understanding the developmental origins of health and disease (DOHaD). The structure of the fetal side of the placental vasculature is an important determinant of fetal growth and cardiovascular development. There are several imaging modalities for assessing feto-placental structure including stereology, electron microscopy, confocal microscopy, micro-computed tomography, light-sheet microscopy, ultrasonography and magnetic resonance imaging. In this review, we present current methodologies for imaging feto-placental vasculature morphology ex vivo and in vivo in human and experimental models, their advantages and limitations and how these provide insight into placental function and fetal outcomes. These imaging approaches add important perspective to our understanding of placental biology and have potential to be new tools to elucidate a deeper understanding of DOHaD.

Quantitative characterization of rodent feto-placental vasculature morphology in micro-computed tomography images.

BACKGROUND AND OBJECTIVE: Optimal development of placental vasculature is critical for fetal growth and health outcomes. Many studies characterizing the vascular structure of the fetal side of the placenta have utilized a range of two-dimensional and three-dimensional (3D) imaging techniques including X-ray micro-computed tomography (micro-CT) following perfusion of the vasculature with a radio-opaque compound. The CT approach has been used to study feto-placental vasculature in rodents and humans. Its inherent advantage is that it reveals the 3D structure in high resolution without destroying the sample. This permits both multiple scanning of the sample and follow-up histological investigations in the same sample. Nevertheless, the applicability of the approach is hampered both by the challenging segmentation of the vasculature and a lack of straightforward methodology to quantitate the feto-placental vascular network. This paper addresses these challenges. METHODS: An end-to-end methodology is presented for automatically segmenting the vasculature; obtaining a Strahler-ordered rooted-tree representation and extracting quantitative features from its nodes, segments and branches (including volume, length, tortuosity and branching angles). The methodology is demonstrated for rat and mouse placentas at the end of gestation (day 22 and day 18, respectively), perfused with Microfil® and imaged using two different micro-CT scanners. RESULTS: The 3D visualizations of the resulting vascular trees clearly demonstrate differences between the branching complexity, tree span and tree depth of the mouse and rat placentas. The quantitative characterizations of these trees include not only the fundamental features that have been utilized in other studies of feto-placental vasculature but also several additional features. Boxplots of several of these-tortuosity, number of side branches, number of offspring per branch and branch volume-computed at each Strahler order are presented and interpreted. Differences and similarities between the mouse and rat casts are readily detected. CONCLUSION: The proposed end-to-end methodology, and the implementation presented using a combination of Amira and Matlab, offers researchers in the field of placental vasculature characterization a straightforward and objective approach for quantifying micro-CT vascular datasets.

Renal microvascular changes in streptozotocin-induced, long-termed diabetic rat.

OBJECTIVE: To investigate the renal microvascular changes in streptozotocin (STZ)-induced, long-termed diabetic rat. MATERIAL AND METHOD: Twelve male Sprague-Dawley rats were used. Each diabetic rat (n = 8) was induced by an intraperitoneal injection of STZ (60 mg/kg) in citrate buffer (pH 4.5). Control rats (n = 4) were injected intraperitoneally with the same amount of the buffer. The animals were sacrificed at 20 weeks after the injections. The kidneys were processed for conventional light microscopy (LM) and vascular corrosion cast technique with scanning electron microscopy (SEM). RESULTS: Under LM, it was found that the glomerular sizes intensively decreased in the long-termed diabetic rat. The thickening of Bowman's basement membrane was demonstrated. Additionally, there were macrophages and capsular drop lesions in renal corpuscles of long-termed diabetes. The sizes of proximal and distal tubules were markedly destroyed, when compared to the control. Moreover, the epithelial necrosis of vacuolated renal tubules was observed. By using vascular corrosion cast with SEM, the glomerular microvascular sizes in the long-termed diabetes were significantly decreased that corresponded to the result under LM. Furthermore, the size of peritubular capillaries decreased. Concerning to vasa recta in the long-termed diabetes, these vessels ran tortuously and decreased in size. CONCLUSION: Renal microvascular changes, observed in STZ-induced diabetic rats, mimic human diabetic nephropathy (DN). Additionally, the pathological changes of the renal tubules were investigated. Therefore, the present study provides an important basic knowledge for understanding the processes in developing DN, as well as for further study of the therapeutic treatment.