mn 3

Lesson 3.1 — Scope & Objectives

• Define every key word supplied in the lesson (genes, chromosomes, gametogenesis, fertilization, implantation, embryo, fetus, placenta, amnion, chorion, yolk sac, viability, teratogen, etc.)
• Describe human gametogenesis (oogenesis & spermatogenesis), fertilization, implantation, and both embryonic & fetal development until birth.

Cellular Basis of Human Development

DNA, Genes & Chromosomes

• Human body cells carry genetic instructions in the nucleus; DNA directs all cellular activities.
• Karyotype: (46) total chromosomes ⇒ (22) pairs of autosomes + (1) pair of sex chromosomes (XX or XY).
• External factors (teratogens, drugs, smoking, under-nutrition, pH) can modify gene expression → congenital anomalies or lifelong disorders.

Two Mechanisms of Cell Division

• Mitosis
– Occurs in somatic (body) cells.
– Single division → 2 identical diploid ( 2n ) daughter cells.
– Enables growth, repair, and general maintenance of tissues.
• Meiosis
– Produces gametes (ova & sperm).
– Two sequential divisions → 4 non-identical haploid ( n ) cells.
– Creates genetic diversity by recombination & independent assortment.

Gametogenesis, Fertilization, & Early Zygotic Changes

Gametogenesis Quick Recap

• Oogenesis: Begins prenatally, pauses at prophase I, resumes with each menstrual cycle, completes only if fertilization occurs.
• Spermatogenesis: Continuous from puberty onwards; millions of sperm/day.

Fertilization

• Definition: Union of one sperm with one ovum → zygote.
• Location: Lateral (outer ⅓) segment of the fallopian tube near the ovary.
• Immediately after penetration: ovum membrane undergoes a chemical block to polyspermy.

Sex Determination

• Ova always carry X chromosome; sperm carry X or Y.
• XX \rightarrow female, XY \rightarrow male.
• The male gamete therefore determines genetic sex.
• pH & mucus viscosity of the female tract affect X-bearing (slower, more resilient) vs Y-bearing (faster, more fragile) sperm survival and motility.

Tubal Transport & Cleavage

• Zygote migrates toward uterus via cilia & peristalsis.
• Rapid mitotic divisions without growth = cleavage.
– 2 → 4 → 8 → 16 cells etc.
– Forms a solid ball of smaller blastomeres called a morula (≈ day 3).
• Fluid entry converts morula into a blastocyst with an inner cell mass (embryoblast) & outer trophoblast.

Implantation

• Typical site: Upper posterior uterine wall.
• Trophoblast enzymes burrow into the receptive endometrium.
• Once implantation occurs, the endometrium is renamed the decidua.
– Area beneath embryo = decidua basalis → maternal side of placenta.

Extra-Embryonic Membranes & Cavities

Chorion

• Outermost fetal membrane; villi extend into decidua basalis.
• Contributes to placental formation.

Amnion & Amniotic Fluid

• Amnion = thin, tough, innermost membrane.
• Amniotic fluid (≈ 500–1000\,mL at term) functions:
– Thermoregulation (even 37\,^{\circ}\mathrm{C} environment).
– Prevents adherence of fetal skin to membranes.
– Permits symmetrical growth & musculoskeletal movement (buoyancy).
– Cushions fetus & umbilical cord from external trauma.
– Reservoir of oral fluid for fetal swallowing → GI maturation.

Yolk Sac

• Appears day 9; transitory.
• First site of hematopoiesis until fetal liver assumes RBC production (~6 weeks).
• Drawn into umbilical cord then degenerates.

Placenta

Development

• Begins with trophoblastic invasion at implantation; anatomically complete 10\text{–}12 weeks.
• Disc-shaped, ~15\text{–}20\,cm diameter, 2\text{–}3\,cm thick, weight ≈ 500–600\,g at term.

Functions

• Respiratory: Diffusion of O2 to fetus; CO2 to mother.
• Nutrition: Glucose (primary fetal fuel), amino acids, fatty acids, vitamins, electrolytes.
• Excretion: Urea, creatinine, bilirubin to maternal blood.
• Endocrine:
– Progesterone: Maintains decidua, decreases uterine contractility, prepares breasts.
– Estrogen (estriol): Stimulates uterine growth & blood flow.
– hCG: Sustains corpus luteum → progesterone until placenta takes over.
– hPL (human placental lactogen): Alters maternal metabolism, promotes breast growth, insulin antagonism.
• Immunologic: Limits fetal exposure to many microbes; provides passive IgG.

Placental Transfer Rule – “AVA”

• Two umbilical Arteries carry deoxygenated fetal blood to placenta.
• One umbilical Vein returns oxygen-rich blood.
• Fetal & maternal blood normally do not mix (micro-villus membrane separates).

Post-Delivery

• Expelled as “afterbirth.”
• Pathological variants (previa, abruption, accreta) threaten mother & fetus.
• Donated placental tissue → bio-dressings for burns & ulcers.

Umbilical Cord

• Forms from connecting stalk during weeks 3–7.
• Composition: 2 arteries + 1 vein embedded in Wharton jelly (mucopolysaccharide matrix) & covered by amnion.
• Average length 55\,cm (range 30\text{–}100) → allows fetal movement; too short/long = complications.
• Functions: Venous flow \rightarrow fetus (oxygen & nutrients); arterial flow \leftarrow fetus (wastes).
• Clamped & cut postpartum; stump falls off within ~2 weeks.

Fetal Circulation vs Postnatal Circulation

• Three shunts let blood bypass lungs & partially liver:

1. Ductus venosus: Umbilical vein → inferior vena cava, bypassing liver.

2. Foramen ovale: Right atrium → left atrium (inter-atrial opening) → systemic circulation.

3. Ductus arteriosus: Pulmonary artery → descending aorta.
   • After birth: Cord clamping increases systemic pressure; first breaths drop pulmonary resistance.
   – Ductus venosus closes → ligamentum venosum.
   – Foramen ovale functionally closes (↑ left-atrial pressure).
   – Ductus arteriosus constricts (↑ PaO₂) → ligamentum arteriosum.

Chronologic Milestones of Fetal Development

• Age of viability: 20 weeks w/ intensive NICU; survival ↑ markedly ≥ 24 weeks (surfactant present).

3–4 Weeks

• Primitive heart tube beats; neural tube forms brain & spinal cord.

7–8 Weeks

• Eyes migrating anteriorly; eyelids appear; palate & tongue begin.
• External genital ridges visible; fetus “human-looking.”

10 Weeks

• Fully formed digits/ears; eyelids fuse; flexion (can make fist) & thumb-sucking begin.

11–14 Weeks

• Nails develop; face well-proportioned; urine produced → amniotic fluid.

15–18 Weeks

• Skin translucent; scalp hair pattern; lanugo forms; “quickening” (maternal perception of movement).

19–21 Weeks

• Functional auditory system; fetus swallows amniotic fluid; more vigorous movement.

22 Weeks

• Lanugo covers body; meconium accumulates in bowel.

26–30 Weeks

• Rapid brain growth; rhythmic breathing motions; eyes reopen ~28 wks.

30–32 Weeks

• CNS gains better temperature & cardio-respiratory control; subcutaneous fat deposition.

Impaired Prenatal Development & Later Disease

• In-utero under-nutrition or hypoxia can "program" permanent changes in organ size, nephron number, pancreatic β-cells, etc.
• Associated adult disorders: hypertension, CAD, type 2 diabetes, obesity (Barker Hypothesis).
• Public health emphasis: Optimize maternal nutrition, avoid teratogens, manage chronic illness to protect next generation.

Multifetal Pregnancy & Types of Twins

• Incidence: Twins ≈ 1 in 90 spontaneous pregnancies; ↑ with ovulation-induction drugs & IVF.
• Monozygotic (Identical)
– One zygote splits → genetically identical; always same sex.
– Timing of split determines chorion/amnion configuration (di-di, mono-di, mono-mono).
• Dizygotic (Fraternal)
– Two separate ova fertilized by two sperm.
– Genetically siblings; may be same or opposite sex; each with its own placenta & membranes.
• Higher-order multiples (triplets, etc.) often involve combo of zygotic types.

Ethical, Clinical & Real-World Connections

• Assisted reproductive technologies raise twin rates → obstetric/fetal risks (preterm, growth restriction).
• Placental insufficiency or abnormal cord insertion calls for Doppler surveillance.
• Stem cells from cord blood & Wharton jelly under research for regenerative medicine.
• Environmental justice: Disparities in exposure to teratogens (e.g., lead, food deserts) translate to inter-generational health gaps.