User:Fishratthings/Teratology

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This is a personal working draft/sandbox for edits towards the Teratology article my group is working on. These will be moved later to my group's sandbox page for the article or into the actual article itself.

Teratogenesis

Principles of teratogenesis

In 1959 and in his 1973 monograph Environment and Birth Defects, embryologist James Wilson put forth six principles of teratogenesis to guide the study and understanding of teratogenic agents and their effects on developing organisms. These principles were derived from and expanded on by those laid forth by zoologist Camille Dareste in the late 1800s:

1. Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with adverse environmental factors.
2. 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.
3. Teratogenic agents act in specific ways on developing cells and tissues to initiate sequences of abnormal developmental events.
4. 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.
5. There are four manifestations of deviant development (Death, Malformation, Growth Retardation and Functional Defect).
6. 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).

Causes

Common causes of teratogenesis include:

• Genetic disorders and chromosomal abnormalities
• Maternal health factors
  • Nutrition during pregnancy (e.g., spina bifida resulting from folate deficiency)
  • Metabolic disorders such as diabetes, malnutrition, and thyroid disorders
  • Stress

• Chemical agents
  • Prescription and recreational drugs (e.g., alcohol, thalidomide)
  • Environmental toxins and contaminants (e.g., heavy metals such as mercury and lead, endocrine disruptors, polychlorinated biphenyls (PCBs))
• Vertically transmitted infections (e.g., rubella, syphllis)
• Ionizing radiation (e.g., X-rays)
• Environmental conditions (e.g., temperature)

Insect larval development

Herbicides containing glyphosate have been noted to disrupt normal larval development in insects.

Examples in other animals

Chick embryo limb development

Thalidomide is a teratogen known to be significantly detrimental to organ and limb development during embryogenesis. It has been observed in chick embryos that exposure to thalidomide can induce limb outgrowth deformities, due to increased oxidative stress interfering with the Wnt signaling pathway, increasing apoptosis, and damaging immature blood vessels in developing limb buds.