Placental Histopathology in the Townes Humanized Mouse Model of Sickle Cell Disease

The Townes mouse model has long served as the gold standard for preclinical investigations of pathologies related to sickle cell disease (SCD) such as acute chest syndrome, chronic kidney disease, and stroke. However, there remain limited reports of their use in investigations of obstetric complications. This is notable given the persistently high risk of adverse pregnancy outcomes in women with SCD, despite improved care. We have previously demonstrated the ability of the Townes model to recapitulate poor pregnancy outcomes analogous to those observed in humans including, reduced embryo growth, placental vascular malperfusion, and increases in fetal and maternal mortality. We now examine placental contributions to these outcomes through histopathological analysis. As such we have identified pathology consistent with ischemic end organ damage in SCD (red cell congestion, vaso-occlusion, vascular fibrosis, etc.), as well as those particularly indicative of adverse pregnancy outcomes (persistence of uterine natural killer cells, hemorrhage, calcium deposition, glycogen and spongiotrophoblast dysregulation, etc.). These findings closely resemble those reported in human studies, further establishing the utility of the Townes model while also emphasizing the significance of placental contributions to adverse pregnancy outcomes.