Teratogenesis, Teratogens and Critical Periods

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Definition

Teratogenesis is the process by which congenital malformations are produced in an embryo or fetus due to exposure to external agents during prenatal development.

• It refers specifically to abnormal development caused by environmental factors, not genetic defects.
• Usually occurs when harmful influences disrupt normal cell proliferation, differentiation, or morphogenesis.

A teratogen is any environmental agent that can cause congenital anomalies or increase their incidence when exposure occurs during pregnancy.

• Teratogens disrupt normal embryonic development, resulting in malformations, growth restriction, or functional deficits.
• Examples: drugs, alcohol, infections, radiation, maternal diseases, nutritional deficits.

Basic Conditions of Teratogenesis

Teratogenesis depends on several fundamental principles:

1. Genotype of the Conceptus & Mother

• Susceptibility is influenced by embryonic/fetal genes and maternal genes.
• Maternal metabolism and placental transport also determine how much of a teratogen reaches the embryo.

2. Developmental Stage at Time of Exposure

• The stage of development is the most critical determinant of the type of defect.
• Different organs have specific windows where they are more vulnerable.

3. Dose & Duration of Exposure

• Teratogens follow a dose-response relationship.
• Higher doses - more severe defects.
• Some have a threshold below which no effect occurs.

4. Mechanism of Action

Teratogens act via specific mechanisms, such as:

• Inducing cell death
• Disrupting cell proliferation
• Altering cell migration
• Interfering with molecular signaling pathways
• Affecting DNA or protein synthesis

5. Access to the Embryo/Fetus

• A teratogen must be able to cross the placenta or otherwise reach the embryo.
• Lipid-soluble, low-molecular-weight substances cross more easily.

6. Manifestations Are Stage-Dependent

• The same teratogen may cause different outcomes depending on timing (ex. death, malformation, growth restriction, or functional deficits).