SN1
SHORT NOTE
5M
★ High-yield
Define teratogen. Describe the critical periods of development and give important teratogens with their effects.
Definition
A teratogen is any agent that can cause a structural or functional abnormality in the developing embryo or fetus.
- About 3% of newborns have a major congenital anomaly; the cause is unknown in half
- Genetic causes account for about 25%, environmental for about 10%, and the rest are multifactorial
Principles of Teratology
- Susceptibility depends on the genotype of the conceptus and of the mother
- Susceptibility depends on the stage at exposure — the single most important principle
- Teratogens act by specific mechanisms on developing cells
Critical Periods
| Period | Timing | Effect of an insult |
|---|---|---|
| Pre-embryonic | Weeks 1–2 | "all OR none" — the conceptus either dies or recovers completely, because the cells are still totipotent |
| Embryonic | Weeks 3–8 | The period OF greatest sensitivity — organogenesis; major structural malformations |
| Fetal | Week 9 to birth | Growth restriction and functional defects, chiefly of the brain; major malformations are unusual |
| Organ | Most sensitive period |
|---|---|
| Central nervous system | Weeks 3–6 (and it remains vulnerable throughout) |
| Heart | Weeks 3–6 |
| Limbs | Weeks 4–7 |
| Eye | Weeks 4–8 |
| Palate | Weeks 6–9 |
| External genitalia | Weeks 7–12 |
Important Teratogens
| Agent | Effect |
|---|---|
| Thalidomide | Phocomelia (limb reduction) — the case that established the science of teratology |
| Alcohol | Fetal alcohol syndrome — growth restriction, microcephaly, short palpebral fissures, smooth philtrum, mental retardation; the commonest preventable cause of mental retardation |
| Phenytoin | Fetal hydantoin syndrome; cleft lip and palate |
| Sodium valproate | Neural tube defects |
| Warfarin | Nasal hypoplasia, stippled epiphyses; replaced by heparin, which does not cross |
| ACE inhibitors | Renal failure, oligohydramnios |
| Tetracycline | Stained teeth and impaired bone growth |
| Isotretinoin | Craniofacial, cardiac and CNS defects; strict contraception required |
| Rubella | Cataract, deafness, cardiac defects (PDA) — the "classic triad" |
| Cytomegalovirus, Toxoplasma | Microcephaly, intracranial calcification, chorioretinitis |
| Maternal diabetes | Caudal regression, cardiac defects, macrosomia |
| Ionising radiation | Microcephaly, growth restriction |
Applied Aspects
- Prescribe in pregnancy only when the benefit outweighs the risk, and prefer drugs with a long safety record
All questions in General Embryology
- Q1Describe gametogenesis. Compare spermatogenesis with oogenesis and add a note on the significance of meiosis. ★
- Q2Describe fertilisation, cleavage and implantation. Add a note on the decidua and ectopic pregnancy. ★
- Q3Describe the events of the second and third weeks of development. Explain gastrulation, the notochord and neurulation. ★
- Q4Describe the derivatives of the three germ layers. Explain the folding of the embryo and add a note on the fetal membranes. ★
- Q5Describe the development, structure and functions of the placenta. Add a note on amniotic fluid. ★
- SN1Define teratogen. Describe the critical periods of development and give important teratogens with their effects. ★
- SN2Describe the types of twinning and their fetal membranes. Add a note on the complications. ★
- SN3Describe the neural tube defects with their causes, diagnosis and prevention. ★
- SN4Describe the development, structure and contents of the umbilical cord. ★
- SN5Describe the chromosomal abnormalities with their mechanisms and clinical features. ★
- SN6Describe the amnion and amniotic fluid with their functions and disorders of volume. ★
- SN7Describe the periods of prenatal development with their milestones. Add a note on the estimation of gestational age.