Transition to extrauterine life and the modeling of perinatal asphyxia in rats

Abstract

Generation of murine models for the study of birth-related pathologies has proven to be a complex and controversial problem. Differences in the relative timing of developmental events of both species have led some researchers to suggest that the rat is born comparatively less developed than the human. The solution proposed to this problem would consist in the delay of the experiments of perinatal asphyxia (PA), usually up to 7–10 days, allowing developmental levels to “equalize” with the human at birth. This solution generates a new set of problems. The developmental milestones in both species follow a divergent temporal pattern. Increasing the age of the rat not only can improve resemblance with humans but also will make the model miss a crucial set of milestones related to birth. During this process, there are specific mechanisms to protect the fetus from neuronal damage, especially those caused by asphyxia. These factors are not present in models where the asphyxia is delayed. In these models, there will be more false positives and more damage that would not be present in humans exposed to PA.