Embryology and Fetal Development
Early Development Timeline
| Stage | Timing | Key Events | |-------|--------|------------| | Fertilisation | Day 0 | Occurs in ampulla of fallopian tube; restores diploid number (46 chromosomes) | | Cleavage | Days 1-3 | Zygote divides without overall growth; morula by day 3 (16 cells) | | Blastocyst | Days 4-5 | Fluid-filled cavity; inner cell mass (embryo) + trophoblast (placenta) | | Implantation | Days 6-10 | Blastocyst implants in posterior upper uterine wall; trophoblast invades endometrium | | Bilaminar disc | Week 2 | Epiblast + hypoblast; "the week of twos" (2 cavities, 2 germ layers) | | Gastrulation | Week 3 | Primitive streak forms; epiblast → 3 germ layers (ectoderm, mesoderm, endoderm); "week of threes" | | Organogenesis | Weeks 3-8 | All major organ systems established; MOST SENSITIVE period for teratogenesis | | Fetal period | Week 9 - birth | Growth and maturation of established organ systems |
Three Germ Layers and Derivatives
- Ectoderm: skin, CNS, neural crest cells, lens, teeth enamel, anterior pituitary (Rathke's pouch)
- Mesoderm: muscle, bone, connective tissue, cardiovascular system, kidneys (mesonephros, metanephros), gonads, adrenal cortex, blood cells
- Endoderm: GI tract lining, liver, pancreas, thyroid, parathyroid, lungs, bladder lining
Development of the Reproductive System
Mullerian (Paramesonephric) Ducts
- Female reproductive tract develops from Mullerian ducts (in absence of AMH)
- Form: fallopian tubes (unfused lateral portions), uterus and upper vagina (fused medial portions)
- Fusion occurs in a caudal-to-cranial direction; resorption of septum creates single uterine cavity
- Lower vagina develops from urogenital sinus (sinovaginal bulbs)
Mesonephric (Wolffian) Ducts
- Male reproductive tract: epididymis, vas deferens, seminal vesicles, ejaculatory ducts
- Wolffian duct remnants in females: epoophoron, paroophoron, Gartner's duct (cyst along anterolateral vaginal wall)
Mullerian Anomalies (ESHRE/ESGE Classification)
| Type | Anomaly | Clinical Features | |------|---------|-------------------| | U0 | Normal | Normal uterus | | U1 | Dysmorphic | T-shaped (DES exposure), infantile | | U2 | Septate | Most common anomaly; associated with recurrent miscarriage; treatable by hysteroscopic septum resection | | U3 | Bicornuate | Two horns with single cervix (partial) or two cervices (complete); associated with preterm labour, malpresentation | | U4 | Hemi-uterus (unicornuate) | One horn developed; may have rudimentary non-communicating horn (risk of ectopic pregnancy) | | U5 | Aplastic/hypoplastic | Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: absent uterus and upper vagina; 46,XX; normal secondary sexual characteristics; normal ovaries | | U6 | Unclassified | |
Sexual Differentiation
Genetic Sex
- Determined at fertilisation: 46,XX (female) or 46,XY (male)
- SRY gene (sex-determining region of Y chromosome): encodes testis-determining factor
- SRY → Sertoli cell differentiation → production of AMH (Anti-Mullerian Hormone)
Gonadal Sex
- Bipotential gonad develops on genital ridge (week 5)
- With SRY: → testis (Sertoli cells + Leydig cells) by week 7
- Without SRY: → ovary (follicular development from week 12)
Phenotypic Sex
- Male: testosterone (from Leydig cells) → Wolffian duct development; DHT (from testosterone via 5-alpha reductase) → external male genitalia; AMH (from Sertoli cells) → Mullerian duct regression
- Female (default pathway in absence of androgens): Mullerian ducts develop; Wolffian ducts regress; external female genitalia develop
Disorders of Sexual Development (DSD)
- Androgen insensitivity syndrome (AIS): 46,XY; complete AIS → female external genitalia, absent uterus (Mullerian ducts regressed by AMH), testes (intra-abdominal or inguinal); raised in female gender; present with primary amenorrhoea and absent uterus
- 5-alpha reductase deficiency: 46,XY; female external genitalia at birth; virilisation at puberty (testosterone effect without DHT); ambiguous genitalia
- CAH (21-hydroxylase deficiency): 46,XX; virilised female external genitalia (ambiguous); normal ovaries and uterus
Gametogenesis
Oogenesis
- Oogonia → primary oocytes: enter meiosis I during fetal life; ARRESTED in prophase I (dictyotene stage) until ovulation
- Meiosis I completed at ovulation → secondary oocyte + first polar body
- Meiosis II completed at fertilisation → ovum + second polar body
- Peak oocyte number: ~7 million at 20 weeks gestation; ~1-2 million at birth; ~300,000-400,000 at puberty; ~400 ovulated in reproductive lifetime
Spermatogenesis
- Begins at puberty; continuous process (64-74 days per cycle)
- Spermatogonia → primary spermatocytes → meiosis I → secondary spermatocytes → meiosis II → spermatids → spermatozoa (maturation in epididymis)
- ~200-300 million sperm produced daily; temperature-sensitive (testes 2-3C below body temperature)
Important Facts for MRCOG
- Organogenesis weeks 3-8: most vulnerable to teratogenesis
- Septate uterus: most common Mullerian anomaly; associated with recurrent miscarriage; surgically correctable
- MRKH: 46,XX, absent uterus/upper vagina, normal ovaries
- SRY gene → testis → AMH (Mullerian regression) + testosterone (Wolffian development) + DHT (external male genitalia)
- AIS: 46,XY, female phenotype, absent uterus, inguinal/abdominal testes
- Oocytes arrested in prophase I from fetal life; complete meiosis I at ovulation
- Peak oocyte count: 7 million at 20 weeks gestation; declines thereafter
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