Embryology — Human Development, Organogenesis and Congenital Anomalies
Quick Review
Embryology is a high-yield topic in INI CET — questions frequently test knowledge of germ layer derivatives, foetal circulation, and common congenital anomalies. Focus on the derivatives of the three germ layers, the neural tube defects, and how foetal circulation differs from adult circulation.
High-Yield Facts for INI CET:
- Ectoderm derivatives: CNS, peripheral nervous system, epidermis, hair, nails, lens of eye, anterior pituitary, enamel of teeth
- Mesoderm derivatives: Muscles, bones, cartilage, blood vessels, kidney, gonads
- Endoderm derivatives: Epithelial lining of GI tract (including liver, pancreas), respiratory tract, bladder, thyroid, thymus
- Foetal shunts: Ductus venosus (bypasses liver), foramen ovale (bypasses lungs), ductus arteriosus (bypasses lungs); all close after birth
Exam tip: Neural tube defects (spina bifida, anencephaly) are associated with folic acid deficiency. The neural tube closes by day 28 — often before a woman knows she’s pregnant. Meckel’s diverticulum is a remnant of the vitelline (omphalomesenteric) duct.
Gametogenesis and Fertilisation
Spermatogenesis
Occurs in seminiferous tubules of testes; takes ~74 days. Spermatogonia (2n) → primary spermatocytes (2n) → secondary spermatocytes (n) → spermatids (n) → spermatozoa (n). Sertoli cells support and nourish developing sperm; form blood-testis barrier. Leydig cells (interstitial cells) produce testosterone; stimulated by LH. Final product: 4 spermatids from 1 primary spermatocyte. Mature sperm has head (nucleus + acrosome containing hyaluronidase for oocyte penetration), neck (centrioles), midpiece (mitochondria), tail (flagellum). Testicular temperature is 2-3°C below body temperature (varicocele causes infertility — increased temperature impairs spermatogenesis).
Oogenesis
Oogonia multiply in fetal life → primary oocytes (arrested in prophase I) → remain dormant until puberty. One primary oocyte completes meiosis I per menstrual cycle → secondary oocyte (arrested in metaphase II) + first polar body. Secondary oocyte completes meiosis II only if fertilised → ovum (n) + second polar body. The oocyte is ovulated as a secondary oocyte surrounded by zona pellucida (glycoproteins ZP1, ZP2, ZP3) and corona radiata (granulosa cells). Follicular atresia: Most follicles degenerate; only ~400-500 ovulated in a reproductive lifetime.
Fertilisation
Occurs in the ampulla of the fallopian tube (widest part). Capacitation: Sperm gains hypermotility in the female reproductive tract (~6 hours). Acrosome reaction: Sperm penetrates corona radiata → binds zona pellucida → acrosome releases enzymes → penetrates zona. Sperm-oocyte membrane fusion → oocyte completes meiosis II → second polar body extruded → female pronucleus forms. Sperm entry triggers the cortical reaction (release of cortical granules from oocyte) → zona reaction (hardening of zona pellucida) → prevents polyspermy. Syngamy: Pronuclei fuse; zygote formed (2n); mitotic cleavage begins.
Cleavage and Implantation
- Day 1: Zygote
- Day 2: 2-cell
- Day 3: Morula (16 cells)
- Day 4: Blastocyst (fluid-filled cavity forms)
- Day 5-6: Hatching from zona pellucida → implants in endometrial wall
Inner cell mass (embryoblast) → embryo proper. Outer cell mass (trophoblast) → placenta. Implantation occurs in the posterior uterine wall with syncytiotrophoblast (secretes hCG) + cytotrophoblast. hCG is detected in maternal blood 8-10 days post-fertilisation; sustains corpus luteum → progesterone → prevents menstruation; basis of pregnancy tests.
Gastrulation and Germ Layer Formation
Gastrulation (Week 3)
Primitive streak forms on epiblast (from caudal end); Hensen’s node (primitive node) at cranial end. Epiblast cells migrate through primitive streak → replace hypoblast → mesoderm and endoderm.
Germ Layer Derivatives:
- Ectoderm (from epiblast): CNS, epidermis, sensory organs, pituitary, adrenal medulla, peripheral nerves
- Mesoderm: Bones, muscles, cartilage, blood vessels, kidney, gonads, spleen, adrenal cortex, dermis, meninges, pleura, pericardium, peritoneum
- Endoderm (from hypoblast): Epithelial lining of GI tract and respiratory tract, liver, pancreas, thyroid, bladder, urethra, vagina, middle ear
Neurulation
Neural plate (ectoderm thickens) → neural folds → neural tube (closes at day 28 — cranial and caudal neuropores close). Neural tube → CNS (brain and spinal cord); neural crest → PNS (dorsal root ganglia, autonomic ganglia, adrenal medulla, melanocytes, meninges, craniofacial cartilage).
Neural Tube Defects:
- Anencephaly: Cranial neuropore fails to close → forebrain and calvaria absent; incompatible with life
- Spina bifida occulta: Vertebral arch fails to close; skin covers; usually lumbar; minimal symptoms
- Myelomeningocele: Vertebral arch + meninges + spinal cord herniate; causes lower limb paralysis, bladder/bowel dysfunction; associated with Arnold-Chiari II malformation
- Meningocele: Meninges herniate but spinal cord is normal
- Folic acid supplementation (400 mcg/day) before conception and during first trimester reduces neural tube defect risk by 50-70%
Pharyngeal Arches and Derivatives
Six pairs of pharyngeal (branchial) arches; each has artery, cartilage, muscle, nerve.
| Arch | Cartilage | Muscles | Nerve |
|---|---|---|---|
| 1 (Mandibular) | Malleus, incus, mandible | Muscles of mastication, mylohyoid, anterior digastric, tensor tympani, tensor veli palatini | V3 |
| 2 (Hyoid) | Stapes, styloid process, lesser horn of hyoid | Stapedius, stylohyoid, posterior digastric, muscles of facial expression | VII |
| 3 | Greater horn of hyoid, lower body of hyoid | Stylopharyngeus | IX |
| 4 | Thyroid cartilage, epiglottic cartilage | Cricothyroid, pharyngeal constrictors | X (superior laryngeal) |
| 5 | Rudimentary; disappears | — | — |
| 6 | Laryngeal cartilages (cricoid, arytenoid, corniculate, cuneiform) | Intrinsic laryngeal (except cricothyroid) | X (recurrent laryngeal) |
Pharyngeal Pouch Derivatives
- 1st pouch → middle ear cavity, Eustachian tube, mastoid air cells
- 2nd pouch → palatine tonsils (lymphoid)
- 3rd pouch → inferior parathyroids + thymus (migrate caudally)
- 4th pouch → superior parathyroids
DiGeorge syndrome: 22q11.2 deletion; failure of 3rd and 4th pouch development → thymic and parathyroid aplasia → hypocalcaemia (tetany), cardiac defects (conotruncal), T-cell deficiency (recurrent infections).
Face Development
Frontonasal process (midline) → nasal placodes (form around nasal pits) → lateral and medial nasal processes. Medial nasal processes → intermaxillary segment → philtrum of upper lip, primary palate, four incisor teeth. Lateral nasal processes → alae of nose. Maxillary processes (from arch 1) → lateral upper lip, secondary palate.
Cleft lip: Failure of fusion between medial nasal process and maxillary process (unilateral or bilateral).
Cleft palate: Failure of fusion of palatine shelves (midline); can be anterior (primary palate) or posterior (secondary palate).
Gastrointestinal Tract Development
Foregut (Coeliac Trunk)
Oesophagus → stomach (rotates 90° clockwise) → duodenum (first part + proximal second part). Liver, gallbladder, pancreas (ventral and dorsal buds). Respiratory system (laryngotracheal diverticulum — outpouching from foregut).
Midgut (SMA)
Distal duodenum → jejunum → ileum → ascending colon → proximal 2/3 of transverse colon. Rotation: 270° counterclockwise around SMA axis. Vitelline (omphalomesenteric) duct connects yolk sac to midgut; if patent → Meckel’s diverticulum (2ft from ileocaecal valve; contains ectopic gastric/pancreatic tissue; follows rule of 2s — 2% of population, 2ft from ileocaecal valve, 2 inches long, presents before age 2, may cause melaena, intussusception, obstruction).
Hindgut (IMA)
Distal 1/3 transverse colon → descending colon → sigmoid → rectum → upper anal canal (above pectinate line). Lower anal canal (below pectinate line): Derived from proctodeum (endodermal invagination).
Urogenital System Development
Kidney Development (Three Successive)
- Pronephros: Non-functional; degenerates
- Mesonephros: Functions temporarily; in males → efferent ductules (connect to testis); in females → degenerates
- Metanephros (permanent): Metanephric mesoderm (forms nephron) + ureteric bud (forms collecting system); ascends from pelvis to lumbar position
Ureteric bud: From mesonephric duct → ureter, renal pelvis, calyces, collecting ducts; causes renal dysplasia if maldevelopment.
Bladder Development
Absorbed from urogenital sinus + mesonephric ducts (trigone from mesonephric ducts). Allantois → urachus → median umbilical ligament.
Sexual Differentiation
- Y chromosome (SRY gene) → testes determining factor → Sertoli cells produce MIS (Anti-Müllerian Hormone) → regresses paramesonephric ducts; Leydig cells produce testosterone → Wolffian duct differentiates; testosterone → DHT → external genitalia male
- No SRY → female development; no MIS → paramesonephric ducts develop; no testosterone → Wolffian regresses; oestrogen → female external genitalia
Paramesonephric (Müllerian) ducts: Female; develop into fallopian tubes, uterus, upper 2/3 of vagina.
Mesonephric (Wolffian) ducts: Male; develop into efferent ductules, epididymis, vas deferens, seminal vesicles, ejaculatory duct.
Congenital Anomalies
- Hypospadias: Urethral opening on ventral penis; due to failure of urethral folds to close (most common anterior); associated with chordee
- Epispadias: Urethral opening on dorsal penis; associated with bladder exstrophy
- Cryptorchidism: Undescended testis; common in premature males; testis should descend by 3 months; increased risk of testicular cancer; corrected with orchidopexy
- Bicornuate uterus: Failure of fusion of paramesonephric ducts → two-horned uterus; associated with recurrent pregnancy loss
- Horseshoe kidney: Lower poles of kidneys fuse across midline; usually asymptomatic; associated with Turner syndrome, trisomy 18
Placenta
Structure
Chorionic villi (branching) — maternal blood in intervillous space (from spiral arteries — high pressure, low resistance); fetal blood in villous capillaries. Placental barrier: Syncytiotrophoblast, cytotrophoblast, basement membrane, CT, fetal capillary endothelium — progressively thins as pregnancy progresses. Chorion frondosum (fetal) + decidua basalis (maternal) = placenta.
Functions
- Exchange: O₂, CO₂, nutrients, waste (by diffusion, facilitated transport, active transport)
- Endocrine: hCG (sustains corpus luteum until 8-10 weeks, then placenta takes over), human placental lactogen (hPL), oestrogen, progesterone
- Immune: IgG crosses placenta (provides passive immunity to fetus)
Umbilical Cord
2 arteries (deoxygenated fetal blood), 1 vein (oxygenated fetal blood to fetus), Wharton’s jelly; inserts into placenta; normal length 40-60cm; may be single umbilical artery (associated with renal anomalies).
Foetal Circulation
Key Differences from Adult
- Ductus venosus: Shunts oxygenated blood from umbilical vein past liver → IVC; bypasses hepatic portal circulation; closes after birth → ligamentum venosum
- Foramen ovale: Hole in atrial septum → shunts blood from right to left atrium → bypasses lungs; closes after birth → fossa ovalis
- Ductus arteriosus: Connects pulmonary artery to aorta → shunts blood from right heart to systemic circulation → bypasses lungs; closes after birth → ligamentum arteriosum
At Birth
- Lungs expand → pulmonary vascular resistance drops → pulmonary blood flow increases
- Left atrial pressure > right atrial pressure → foramen ovale closes (functional closure)
- Increased O₂ → ductus arteriosus constricts → functional closure within 24-48h
- Umbilical vessels constrict → ductus venosus closes
- All foetal shunts become ligaments: Ligamentum venosum, fossa ovalis, ligamentum arteriosum
Twins
- Monozygotic (identical): Single fertilised ovum splits; share same genotype; can be dichorionic/diamniotic, monochorionic/diamniotic, or monochorionic/monoamniotic (late split — high risk)
- Dizygotic (fraternal): Two ova fertilised by two sperm; different genotypes; always dichorionic/diamniotic
- Vanishing twin: One embryo reabsorbs; more common with ART; may cause bleeding in first trimester