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Saturday, December 20, 2014

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The Six Principles of Teratology

These principles of teratology were put forth by Jim Wilson in 1959 and in his monograph Environment and Birth Defects. These principles guide the study and understanding of teratogenic agents and their effects on developing organisms:

  • Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with adverse environmental factors.
  • Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence. There are critical periods of susceptibility to agents and organ systems affected by these agents.
  • Teratogenic agents act in specific ways on developing cells and tissues to initiate sequences of abnormal developmental events.
  • The access of adverse influences to developing tissues depends on the nature of the influence. Several factors affect the ability of a teratogen to contact a developing conceptus, such as the nature of the agent itself, route and degree of maternal exposure, rate of placental transfer and systemic absorption, and composition of the maternal and embryonic/fetal genotypes.
  • There are four manifestations of deviant development (Death, Malformation, Growth Retardation and Functional Defect).
  • Manifestations of deviant development increase in frequency and degree as dosage increases from the No Observable Adverse Effect Level (NOAEL) to a dose producing 100% Lethality (LD100).


Studies designed to test the teratogenic potential of environmental agents use animal model systems (e.g., rat, mouse, rabbit, dog, and monkey). Early teratologists exposed pregnant animals to environmental agents and observed the fetuses for gross visceral and skeletal abnormalities.

While this is still part of the teratological evaluation procedures today, the field of Teratology is moving to a more molecular level, seeking the mechanism(s) of action by which these agents act. Genetically modified mice are commonly used for this purpose. In addition, pregnancy registries are large, prospective studies that monitor exposures women receive during their pregnancies and record the outcome of their births. These studies provide information about possible risks of medications or other exposures in human pregnancies.

Understanding how a teratogen causes its effect is not only important in preventing congenital abnormalities but also has the potential for developing new therapeutic drugs safe for use with pregnant women.

Teratology

 

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