Anatomy and Physiology of the Developing Mouse and Placenta

Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 Figure 9 Figure 12 Figure 14 Figure 16 Figure 17

The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.

The placenta of eutherian mammals is a remarkable biological structure. It is composed of both zygote-derived and maternal cells, and mediates the complex interactions between the mother and the fetus that are necessary for fetal growth and survival. While the genetic basis of human placental development and function is largely unknown, its understanding is of immense clinical importance because placentopathies of unknown genetic aetiology are thought to be the cause of many types of pregnancy complications including unexplained miscarriage and intrauterine growth retardation. The mouse is the best-studied mammalian experimental genetic model system and research is not restricted by the inherent ethical and practical limitations associated with the human. As a result, knowledge about the genetic control of mouse placental development has expanded greatly in recent years. In order for this to be of benefit to medical practice, extrapolations from murine to human placentation have to be made. However, comprehensive comparisons of the placentae of these two species are rare. This review therefore compares the developmental anatomy of the placenta between humans and mice with emphasis on structures and cell types that might be analogous between the two species. This could be of particular benefit to mouse developmental geneticists who study placental development and have an interest in the possible clinical implications of their work. Copyright 2002 Harcourt Publishers Ltd.