Perinatal Development: Misunderstood Biology That Can Lead Hazard Assessment Astray

Gestation periods of rodents and humans differ dramatically. Due to their brief time in utero, rodent offspring develop faster than humans, but at birth they are considerably less developmentally mature than human neonates. Because fetuses are harvested near-term in embryo-fetal development studies, some fetuses which lag others in developmental schedules may be characterized as malformed. However, if allowed to continue, many deficits in developmental timing would be eliminated quickly during the early lactational period. Consequently, it is important to appreciate the perinatal development of test species to inform interpretation of test results.

This paper reviews the comparative timing as well as pre and postnatal development of exemplar organs for the purpose of providing context in interpreting rodent data and extrapolating them to human hazard assessment. The selected organs and developmental processes include ossification of the skeleton; septation of the cardiac atria and ventricles; surfactant synthesis in the lung; establishment of the intestinal lining and maturation of gastrointestinal absorption; myelination of the brain and establishment of the blood-brain barrier.

Comparative perinatal biology should be used in interpreting rodent test data to avoid mis-classifying substances. Due to the compressed development schedule of rodents compared with humans, delays in rodent development may be misinterpreted as malformations. Delays in lung maturation may explain some cases of early deaths in normally appearing rat pups. Invoking perinatal biology does not obviate study findings, but it can provide context that informs interpretation.