Pathology of Genetically Engineered and Other Mutant Mice. Группа авторов
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GD = gestational day (where GD0 is the vaginal plug‐positive day).
Figure 5.22 Schematic representation of structurally distinct lesion patterns whereby placental labyrinth dysfunction leads to intrauterine growth restriction (IUGR) or embryonic lethality. In a normal placenta (a), the labyrinth (long black vertical bar) is the largest zone permitting exchange of gases and nutrients between the embryonic blood spaces (EBS) and maternal blood spaces (MBS). Reduced labyrinth volume (b, small red vertical bar) or reduced vascular complexity (c) typically indicate decreased numbers and/or altered organization of EBS and/or MBS, thus decreasing the vascular surface area available for exchange. Interhemal barrier defects (d) generally reflect abnormal density and/or function of one or more embryonic trophoblast layers, thereby increasing the tissue thickness across which nutrients and gases must be transported. Tissue or vascular disruption (e), such as local or multifocal fibrosis or necrosis and/or intravascular thrombosis, may both block blood flow and destroy vascular surface area needed for gas and nutrient exchange. Multinucleated trophoblast giant cell (mTGC) formation (f) results from a trophoblast differentiation defect in which improper cell fusion disturbs labyrinth organization.
Source: Woods et al. [95]. License under a Creative Commons 4.0 International License.
Figure 5.23 Common lesions in the placental labyrinth of mouse embryos may affect specific cell lineages or all cell populations in a region. Panel (a): Trophoblast hyperplasia appears as coalescing aggregates of plump basophilic cells, some of which contain mitotic figures. Panel (b): Virus‐induced endothelial cell necrosis in embryonic blood spaces (EBS) presents as abundant cell debris in vascular channels that also contain a few large‐diameter, nucleated erythrocytes. Panel (c): The EBS are packed with long, linear plugs of necrotic debris, which represent emboli of degenerating cells arising from the dying embryo. Panel (d): Widespread necrosis, hemorrhage, and fibrin deposition blurs the labyrinth structure and effaces many EBS. Stain: H&E.
Summary
Developmental phenotypes in embryonic and neonatal mice may be evaluated readily by comparative pathologists using routine macroscopic (gross observations and measurements of whole‐animal or organ dimensions, volumes, or weights) and microscopic (light microscopy) techniques. If available, interpretation of such conventional endpoints is aided substantially by integration with other classes of data such as digital files acquired by noninvasive imaging or molecular expression profiles obtained from homogenized tissue samples or specially stained tissue sections. Lesions in embryos (and/or placentas) and neonates exhibit different patterns depending on when during development damage occurs in the conceptus. Genetic mutations, infectious agents, and toxicants all can adversely impact developing tissues, and can elicit comparable patterns of cell and tissue damage. The rapid anatomic and biochemical evolution in both space and time that takes place throughout the course of development ensures that the analysis of a potential lethal phenotype usually will be a complicated endeavor, requiring both patience and skill in designing the analytical strategy. Successful projects require an initial determination of the time of death followed by identification and detailed characterization of anatomic changes, functional abnormalities, and their molecular bases. Investigators should be prepared to acknowledge that a certain number of projects ultimately may fail to determine a cause for the developmental lethality.
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