Developmental Toxicology Background
For those with visual impairments click for audio:
|
|
![Picture](/uploads/4/6/9/9/46993675/2635988.jpg?315)
Developmental toxicology is defined as the study of the effects of tetragens on the developing embryo. A teratogen is defined as any agent that can lead to a congenital anomaly or give rise to the incidence of an anomaly in a population. Although the developing embryo is protected by the uterus, maternal exposure to these agents can lead to developmental disruptions. Approximately 7-10% of congenital anomalies are caused by environmental factors like drugs and infections. Unfortunately, the exact mechanisms by which these factors disrupt embryonic development and induce anomalies remains unknown. Progress in molecular biology, however, is providing more information regarding the genetics of pattern formation and development and therefore more information of the molecular targets of teratogens.
Development is most important when processes such as cell division, differentiation and morphogenesis are at their peak. Any disturbances in the surrounding environment during the first two weeks of development can interfere with cleavage of the zygote or implantation of the blastocyst. This results in either early death or spontaneous abortion. Toxins that act during this period either kill the embryo or their disruptive effects are compensated by powerful regulatory properties.
Stages of development:
The embryonic period occurs during weeks 3 - 8 and this is this time when the tissues and organs are forming. Thus, this organogenesis period, is a vulnerable time in development and if toxins are introduced, they may induce major congenital anomalies. Each of the tissues and organs have a critical period during which development can be disrupted.
Weeks 3-16 are the most critical in terms of brain development. However, the brain continues to grow and differentiate from birth and throughout the first two years at least and so development can still be disrupted by tetragens after the 16 weeks.
Disruption to embryonic development during the fetal period, weeks 9-38, can result in minor morphological anomalies, physiological defects and functional disturbances such a mental retardation.
Wilsons' Principle's
Based on Wilsons principles, the susceptibility to teratogens will depend on the genotype of the conceptus and the way in which this interacts with other environmental factors. Susceptibility itself will vary depending on the stage of development at the time of exposure to the teratogen. Toxic agents act in different ways to induce abnormal embryogenesis depending on the cells and tissues involved. The four manifestation of abnormal development are death, malformations, growth retardation and functional disorders. Manifestations of deviant development will increase in severity as dosage of the teratogen also increases from the no effect to the lethal level.
Based on Wilsons principles, the susceptibility to teratogens will depend on the genotype of the conceptus and the way in which this interacts with other environmental factors. Susceptibility itself will vary depending on the stage of development at the time of exposure to the teratogen. Toxic agents act in different ways to induce abnormal embryogenesis depending on the cells and tissues involved. The four manifestation of abnormal development are death, malformations, growth retardation and functional disorders. Manifestations of deviant development will increase in severity as dosage of the teratogen also increases from the no effect to the lethal level.