Chapter 29 – Development, Growth, Aging & Genetics

Prenatal Development

• Three chronological subdivisions (conception → birth)
  • Germinal period—first 2 weeks after fertilization
    • Zygote forms primitive germ layers.
  • Embryonic period—3\text{–}8 weeks post-fertilization
    • Organ systems initially appear; developing human = embryo.
  • Fetal period—last 30 weeks (≈ day 60 → birth)
    • Organ systems grow & mature; developing human = fetus.
• Age-tracking conventions
  • Clinical age—dated from last menstrual period (LMP).
  • Post-ovulatory age—clinical age − 14 days (more precise for embryology).

Fertilization Mechanics

• Site & participants
  • Location = ampulla of uterine tube.
  • Secondary oocyte surrounded by corona radiata + zona pellucida (ZP).
  • Several 10^8 sperm deposited; only ≈ dozens reach oocyte.
• Penetration sequence
  1. Flagellar action pushes sperm through corona radiata.
  2. Sperm binds ZP3 receptor in zona pellucida → acrosomal reaction releases hyaluronidase & other enzymes.
  3. First sperm to traverse ZP binds integrin \alpha 6\beta 1 on oocyte membrane → membrane depolarization within 2\text{–}3\ \text{s} (fast block to polyspermy).
  4. Ca^{2+} surge → cortical granule exocytosis → water influx → ZP denatures/expands → ZP3 inactivated, creating perivitelline space (slow block).
  5. Oocyte completes meiosis II → second polar body + haploid female pronucleus.
  6. Male and female pronuclei fuse → diploid zygote (restores 2n chromosome number).

Early Cleavage & Blastocyst Formation

• Cleavage divisions—1 \rightarrow 2 \rightarrow 4 \rightarrow 8 cells (days 1\text{–}3).
  • Early blastomeres are totipotent—each can form an entire embryo (basis of monozygotic twins if separated).
  • Later become pluripotent—capable of many, but not all, cell fates.
• Morula—solid ball ≥ 12 cells (≈ day 5).
• Blastocyst—hollow sphere with blastocele (day 6).
  • Trophoblast (single‐cell layer) → placenta + extra-embryonic membranes.
  • Inner cell mass → embryo proper.
  • Implantation begins when blastocyst contacts endometrium.

Implantation & Placenta Development

• Trophoblast differentiation
  • Cytotrophoblast—mitotically active cells adjacent to inner cell mass; later form chorionic villi cords.
  • Syncytiotrophoblast—multinucleate invasive front; non-antigenic; erodes endometrium.
• Lacunae formation (≈ days 14\text{–}20)
  • Syncytiotrophoblast digests maternal arterioles → blood-filled cavities (lacunae) continuous with maternal circulation.
• Chorionic villi & mature placenta
  • Cytotrophoblast cords + extra-embryonic mesoderm grow into lacunae → villi containing embryonic capillaries.
  • As placenta matures, cytotrophoblast layer regresses; barrier = fetal capillary endothelium + basement membrane + thin syncytiotrophoblast—efficient exchange yet no direct blood mixing.

Formation of Extra-Embryonic Cavities & Germ Layers

• Amniotic cavity—within inner cell mass; lined by amnion; ultimately surrounds embryo in protective fluid.
• Yolk sac—forms from hypoblast lining blastocele; site of early blood formation & primordial germ cells.
• Embryonic (bilaminar) disk—epiblast + hypoblast.

Gastrulation (Primitive Streak)

• Epiblast cells migrate through primitive streak (caudal → cephalic) forming three germ layers:
  • Ectoderm (non-migrating epiblast).
  • Mesoderm (cells migrating between layers).
  • Endoderm (cells displacing hypoblast).

Neurulation

• Neural plate (≈ day 18) induced by notochord within ectoderm near cephalic end.
• Neural folds elevate → fuse midline (day 26) forming neural tube (future brain & spinal cord).
  • Failure to close → neural tube defects.
• Neural crest cells at fold crests detach; derivatives include sensory & autonomic ganglia, adrenal medulla, melanocytes, craniofacial bones, connective tissue, some head muscles.

Embryonic Folding & Digestive Tract

• Lateral & cephalocaudal folding converts flat embryo into tubular form (days 20\text{–}30).
  • Foregut & hindgut form at cephalic/caudal ends; still connected via yolk stalk (midgut).
  • Oropharyngeal membrane → mouth; cloacal membrane → anus & urethral opening.

Germ Layer Derivatives (selected highlights)

• Ectoderm: epidermis, tooth enamel, lens/cornea, anterior pituitary; neuroectoderm → CNS; neural crest → PNS, adrenal medulla, facial bones, dentin.
• Mesoderm: dermis, muscle, bones (axial/appendicular), cardiovascular & lymphatic systems, kidneys.
• Endoderm: epithelial lining of digestive & respiratory tracts, liver ducts, pancreas ducts, bladder, thymus, thyroid, parathyroids, tonsils.

Organogenesis Timeline (weeks 3\text{–}8)

• Week 3 (days 16\text{–}20)
  • Somites, blood islands, two-tubed heart, thyroid primordium, neural plate.
• Week 4 (days 21\text{–}25)
  • Neural tube closure, eye/ear rudiments, beating single-tubed heart, diaphragm begins.
• Week 5 (days 26\text{–}30)
  • Limb buds, melanocyte migration, lens induction, parathyroid/pancreas buds, interatrial septum, lung buds, liver & pancreas enlargement, mesonephros kidneys, genital tubercle.

Fetal Period (day 60 → birth)

• Rapid growth in size & mass.
• Continued maturation of organ systems established during embryonic phase.

Parturition (Labor & Delivery)

• Hormonal cascade
  1. Late pregnancy: high progesterone keeps uterus quiescent.
  2. Estrogen levels rise sharply → override progesterone inhibition.
  3. Fetal stress (crowding, hypoxia) → hypothalamic CRH → fetal pituitary ACTH → fetal adrenal glucocorticoids.
  4. Glucocorticoids act on placenta: ↓ progesterone, ↑ estrogen + prostaglandins → uterine excitability.
• Positive feedback loop
  • Cervical stretch → maternal posterior pituitary releases oxytocin → stronger uterine contractions → more stretch, until birth.
• Stages of labor
  • First stage: regular contractions → cervix dilation to fetal head diameter; rupture of amniotic sac possible.
  • Second stage: maximal dilation → expulsion of fetus.
  • Third stage: delivery of placenta.

Neonatal Cardiopulmonary Adjustments

• Shunt closures (within 1\text{–}2 days)
  • Ductus arteriosus → ligamentum arteriosum (local O_2, pressure changes).
  • Foramen ovale → fossa ovalis (left-atrial pressure ↑ after lung expansion).
  • Ductus venosus → ligamentum venosum; umbilical vein → round ligament (ligamentum teres); umbilical arteries → fibrous cords.
• Result: separation of pulmonary & systemic circuits; liver perfusion established.

Lactation Physiology

• Breast changes during pregnancy
  • Duct proliferation + adipose deposition; alveolar epithelial cells differentiate under estrogen, progesterone, prolactin, hPL.
• Milk production (prolactin) vs. milk ejection (oxytocin).
  • Suckling → afferent signals to hypothalamus.
  • Hypothalamus: ↓ dopamine (prolactin-inhibiting hormone) & ↑ stimulation of posterior pituitary.
  • Anterior pituitary releases prolactin → alveolar cells synthesize milk.
  • Posterior pituitary releases oxytocin → myoepithelial contraction → milk letdown; can be triggered by infant cry (conditioned reflex).
• Colostrum—first 2\text{–}3 days postpartum; protein-rich, antibody-rich, low fat; primes neonatal gut & immunity.

Ethical & Clinical Connections

• Assisted reproductive technologies manipulate totipotent/pluripotent stages; raises considerations about embryo status.
• Teratogen vulnerability highest during organogenesis (weeks 3\text{–}8); pharmacologic & environmental exposures must be minimized.
• Failure of neural tube closure underscores importance of maternal folate supplementation.
• Patent ductus arteriosus (PDA) requires pharmacologic (indomethacin) or surgical closure to prevent pulmonary hypertension.

Summary Equations & Values

• Time conversions: 1\ \text{week}=7\ \text{days}.
• Post-ovulatory age = clinical age − 14\ \text{days}.
• Gestational term ≈ 40 clinical weeks (≈ 38 post-ovulatory weeks).