Human Reproduction, Development and Ageing - Lecture 1 Notes

Contemporary Research Highlights (illustrating real-world relevance)

• Uterus Transplantation:
  • Australia’s first uterus-transplant recipient pregnant weeks post-surgery.
  • Global data: $\approx 80$ transplants ⇒ $\approx 40$ live births.

• Anti-Ageing Gene Editing:
  • Naked-mole-rat hyaluronic-acid gene prolongs mouse lifespan, slows ageing, reduces cancer.

• Synthetic Embryos & Early Gene Activation:
  • Stem-cell-derived human embryo-like structures advanced to $\sim$ $14$-day stage.
  • Genes switch on immediately post-fertilisation; mechanism may mediate inheritance of acquired traits (e.g. obesity).

• IVF & Embryo Selection:
  • Nature Cell Biology study: embryos labelled “abnormal” by standard genetic test still self-correct & yield healthy births; calls test “obsolete”.

• STI Trends:
  • Syphilis cases ↑ $32\%$ from $2020$→$2021$ (highest in $70$ yrs); Australia faces similar surge, esp. Northern/Central/Western regions.

Cellular Fundamentals

• Human cell components: microvilli, cytoskeleton, centrioles (centrosome), cilia, ribosomes, mitochondria, ER, Golgi, lysosomes, peroxisomes, proteasomes, nucleus (envelope, pores, chromatin, nucleolus).

• Organelles grouped:
  • Non-membranous: cytoskeleton, microvilli, centrioles, cilia, ribosomes.
  • Membranous: mitochondria, ER (rough & smooth), Golgi, lysosomes.

• Interphase nucleus: DNA = uncoiled “chromatin”.

Human Chromosome Numbers & Terminology

• Somatic cells: $46$ chromosomes (diploid = $2n$) arranged as $23$ homologous pairs (one paternal, one maternal).

• Gametes: $23$ single chromosomes (haploid = $n$).

• Fertilisation: $n + n \to 2n$ restores diploid number.

• Chromosome anatomy:
  • Each duplicated chromosome = $2$ sister chromatids joined at a centromere.
  • Arms designated short (p) & long (q).

Mitosis (Growth & Repair)

• Purpose: create $2$ genetically identical daughter cells. Cells that DON’T divide mitotically: neurons, mature gametes.

• Phases (continuous process; mnemonic “PMAT”):

  1. Prophase
     • DNA coils/condenses; $92$ chromatids visible (still $46$ chromosomes).
     • Nuclear envelope & nucleolus fragment.
     • Centrosomes migrate to poles; spindle begins forming.

  2. Metaphase
     • Nuclear envelope gone.
     • Spindle microtubules attach to each centromere via kinetochores.
     • Chromosomes align on equatorial “metaphase plate”.

  3. Anaphase
     • Centromeres split—sister chromatids now independent chromosomes (disjunction).
     • Spindle shortens, pulling chromosomes to opposite poles.

  4. Telophase
     • Chromosomes reach poles; nuclear envelopes re-form.
     • Spindle disassembles; cytokinesis cleaves cytoplasm, producing $2$ identical diploid cells.

Meiosis (Reductional Division)

• Ensures gametes are haploid so fertilisation restores diploid number; occurs in spermatocytes & oocytes.

• Two successive divisions: Meiosis I (reductional) & Meiosis II (equational). DNA replication only before Meiosis I.

Meiosis I Detailed

1. Interphase I: DNA replication.

2. Prophase I (most complex):
   • Homologous chromosomes pair (synapsis) → bivalents/tetrads ($4$ chromatids).
   • Crossing-over at chiasmata between non-sister chromatids → genetic recombination.
   • Centrioles migrate; spindle forms; nuclear envelope breaks down.

3. Metaphase I: bivalents align on equatorial plane with centromeres facing opposite poles; independent assortment ( 2^{23} > 8 million possible orientations).

4. Anaphase I: homologous centromeres separate; each pole receives $23$ duplicated chromosomes (disjunction).

5. Telophase I / Cytokinesis: cells become haploid ($n = 23$), chromosomes uncoil slightly; cleavage yields $2$ cells.
   • Males: equal cytoplasm.
   • Females: unequal → secondary oocyte + first polar body.

Interphase II

• Brief “interkinesis”; NO DNA replication.

Meiosis II (resembles mitosis)

1. Prophase II: chromatids condense; spindle reforms.

2. Metaphase II: chromosomes line up singly on metaphase plate.

3. Anaphase II: centromeres split; sister chromatids (now chromosomes) pulled apart.

4. Telophase II / Cytokinesis: nuclei re-form, chromosomes uncoil → total products: $4$ haploid cells.

Gametogenesis Differences

• Males (Spermatogenesis):
  • Spermatogonium → primary spermatocyte ($46$) → $2$ secondary spermatocytes ($23$) → $4$ spermatids ($23$) → $4$ mature spermatozoa.
  • Products: $2$ with X, $2$ with Y chromosome.

• Females (Oogenesis):
  • Oogonia proliferate during fetal life; by birth $1$–$2$ million primary oocytes (in primordial follicles).
  • Childhood: many undergo atresia; $\approx$ $40,000$ remain at puberty.
  • Primary oocyte (arrested Prophase I) completes Meiosis I just before ovulation → secondary oocyte (arrested Metaphase II) + first polar body.
  • Meiosis II completed only if sperm penetration occurs, yielding mature ovum + second polar body.

• Cytoplasmic allocation: females give virtually all cytoplasm to the single ovum; polar bodies tiny & degenerate.

• Lifetime ovulations: $\approx 400$–$500$ secondary oocytes released; few reach full maturity.

Follicle Development Terms

• Primordial → primary → growing (multiple granulosa layers) … Graafian (vesicular) follicle.

• Zona pellucida = glycoprotein layer around oocyte; corona radiata = granulosa cells adherent to zona.

Karyotypes & Non-Disjunction Syndromes

• Karyotype: visual chromosome set; normal = $46$,XX (female) or $46$,XY (male). Classification by size & centromere position.

• Non-disjunction: failure of homologous chromosomes (Anaphase I) or sister chromatids (Anaphase II) to separate → aneuploidy.

• Key syndromes:
  • Down (Trisomy $21$): karyotypes $47,XX,+21$ or $47,XY,+21$ (short stature, round face, epicanthic folds, intellectual disability).
  • Turner (Monosomy X): $45,X$ or $45,XO$ (phenotypic female, sterile, short, webbed neck, horseshoe kidney, broad chest).
  • Klinefelter: $47,XXY$ (phenotypic male, tall, small testes, gynaecomastia, female-type fat distribution, sterile).

Learning Outcomes Recap (Lecture $1$)

• Distinguish mitosis vs meiosis & relate meiosis to gametogenesis (male & female).

• Identify errors in meiosis leading to aneuploid syndromes; describe associated characteristics.