High-resolution contrast-enhanced microCT reveals the true three-dimensional morphology of the murine placenta

Abstract

Genetic engineering of the mouse genome identified many genes that are essential for embryogenesis. Remarkably, the prevalence of concomitant placental defects in embryonic lethal mutants is highly underestimated and indicates the importance of detailed placental analysis when phenotyping new individual gene knockouts. Here we introduce high-resolution contrast-enhanced microfocus computed tomography (CE-CT) as a nondestructive, high-throughput technique to evaluate the 3D placental morphology. Using a contrast agent, zirconium-substituted Keggin polyoxometalate (Zr-POM), the soft tissue of the placenta (i.e., different layers and cell types and its vasculature) was imaged with a resolution of 3.5 µm voxel size. This approach allowed us to visualize and study early and late stages of placental development. Moreover, CE-CT provides a method to precisely quantify placental parameters (i.e., volumes, volume fraction, ratio of different placental layers, and volumes of specific cell populations) that are crucial for statistical comparison studies. The CE-CT assessment of the 3D morphology of the placentas was validated (i) by comparison with standard histological studies; (ii) by evaluating placentas from 2 different mouse strains, 129S6 and C57BL/6J mice; and (iii) by confirming the placental phenotype of mice lacking phosphoinositol 3-kinase (PI3K)-p110α. Finally, the Zr-POM–based CE-CT allowed for inspection of the vasculature structure in the entire placenta, as well as detecting placental defects in pathologies characterized by embryonic resorption and placental fusion. Taken together, Zr-POM–based CE-CT offers a quantitative 3D methodology to investigate placental development or pathologies.

Effect of Maternal Obesity in Mice on IL-6 Levels and Placental Endothelial Cell Homeostasis

“…Fetus position within the uterine horn in rodent animal models has been described as an important factor in feto-placental development [34] and the variation in fetal weight per conceptus in our mouse model further supports the rational that each fetus with its respective placenta is biologically distinct. Additionally, it has recently been suggested that dimorphisms, e.g., placental and fetal sex, exist which have an impact on placental development and fetal growth [35,36]. Furthermore, when collecting physiological data from embryos in utero or investigating feto-placental units in genetically modified dams, differences between each feto-placental unit can be observed regarding heart rate [37] or normal fetal development independent of fetal genotype [38], respectively, suggesting that analyzing multiple placentas per dam could be appropriate.…”

3D virtual pathohistology of lung tissue from Covid-19 patients based on phase contrast X-ray tomography

“…, 1200 projections of exposure time with a flat panel CMOS detector with Gadox-scintillator, PerkinElmer, USA) (Bartels et al, 2013). Metal-staining (here UA) of the lung tissue helped to achieve sufficient contrast, similar to previous CT-studies of other biological tissues (Müller et al, 2017;Busse et al, 2018;De Clercq et al, 2019). The resulting overview scans could also be correlated well with histological sections.…”

Skp2 contributes to cell cycle progression in trophoblast stem cells and to placental development

“…Although the mechanism by which the phenotype of the Skp2 −/− mouse placenta is influenced by genetic background is unclear, one possibility is that mice on the C57BL/6 background are more susceptible to the development of placental defects. Placental morphology differs between the C57BL/6‐ and 129/SvJ‐inbred strains (De Clercq et al., 2019; Tunster, Pette, & John, 2012). Placental volume of C57BL/6 mice is larger than that of 129/SvJ mice, although fetal weight is similar in the two strains.…”