Page 2 of 3

AN76.1-2 | Introduction to embryology — Self-Directed Learning

Embryology: Definitions and Subdivisions

Embryology (Greek: embryon = to swell; logos = study) is the science of the development of an organism from fertilisation to birth.

Key subdivisions
- Descriptive embryology: describes the sequence of developmental events
- Comparative embryology: compares development across species (evolutionary insights)
- Experimental embryology: manipulates embryos to understand developmental mechanisms
- Chemical/Molecular embryology: studies genes, signalling molecules, and their roles
- Teratology: study of developmental abnormalities (Greek: teras = monster)
- Clinical embryology: direct application to medicine — ART, prenatal diagnosis, foetal surgery

Periods of Human Development

Period	Duration	Key Events
Pre-embryonic	Weeks 1–2	Fertilisation → cleavage → morula → blastocyst → implantation → bilaminar disc
Embryonic	Weeks 3–8	Gastrulation → neurulation → organogenesis; all major organ systems established
Foetal	Week 9 – birth	Growth, differentiation, maturation of established systems

Why the Embryonic Period (Weeks 3–8) is Critical
Organogenesis — the formation of all major organ systems — occurs during weeks 3–8. This is the period of maximum vulnerability to teratogens. Exposure before implantation (week 1–2) tends to cause an all-or-nothing effect (embryo dies or survives unaffected). After week 8, teratogens mainly affect growth and CNS maturation.

Gestational Age vs Fertilisation Age
- Fertilisation (developmental) age: counted from day of fertilisation — accurate but impractical
- Gestational (menstrual) age: counted from first day of last menstrual period (LMP) — used clinically
- Gestational age = Fertilisation age + 2 weeks (assumes 28-day cycle, ovulation at day 14)
- Full-term pregnancy: 40 weeks gestational age = 38 weeks developmental age

Teratology: Critical Periods and Causes

Teratogen: any agent that can disturb the development of an embryo or foetus, causing structural abnormality, growth restriction, or intellectual disability.

Wilson's Six Principles of Teratology (1959)
1. Susceptibility depends on genotype of embryo
2. Susceptibility varies with developmental stage at time of exposure
3. Teratogens act by specific mechanisms on developing cells
4. Final manifestations are death, malformation, growth retardation, or functional deficit
5. Access to developing tissues depends on nature of teratogen
6. Dose-response relationship exists

Critical Periods by System
- Heart: weeks 3–7 (most sensitive: weeks 4–6)
- Brain/neural tube: weeks 3–6
- Upper limb: weeks 5–6 (hand plates appear week 6)
- Lower limb: weeks 5–7
- Eyes: weeks 4–8
- External genitalia: weeks 7–12 (still sensitive to androgens until birth)
- Palate: weeks 7–12

Classification of Teratogens

Drugs:
- Thalidomide: phocomelia (limb reduction defects) — peak sensitivity weeks 4–6
- Isotretinoin (Vitamin A derivatives): craniofacial, cardiac, CNS defects
- Valproate: neural tube defects, craniofacial anomalies
- Warfarin (weeks 6–9): nasal hypoplasia, stippled epiphyses
- Alcohol: foetal alcohol spectrum disorder (FASD) — MOST COMMON preventable cause of intellectual disability worldwide
- ACE inhibitors (2nd/3rd trimester): renal dysgenesis, oligohydramnios
- Misoprostol (if MTP fails): Möbius syndrome, limb defects

Infections (TORCH):
- Toxoplasma, Rubella (weeks 5–16 → cataracts, deafness, cardiac), CMV (most common congenital viral infection), HSV, Syphilis, Zika (microcephaly)

Radiation: >100 mGy → microcephaly, intellectual disability; diagnostic X-rays rarely reach this dose

Maternal Conditions: Poorly controlled diabetes → caudal regression syndrome, cardiac defects; hypothyroidism → cretinism

Mechanical: Amniotic bands → limb amputations, facial clefts