Fertilisation

Question 1

What does fertilisation require?

Answer 1

• A mature egg
• A mature sperm
• Fusion of these two in the ampullary region of the oviduct

Question 2

What are the roles of Ca2+ in fertilisation?

Answer 2

• Required for the acrosome reaction
• Cortical granule exocytosis
• The cell cycle

Question 3

What is capacitation of sperm?

Answer 3

• This allows sperm to penetrate the zona pellucida
• The sperm tail becomes fully functional and mobile to enable hyper-activated motility
• It also allows for the acrosome reaction to occur

Question 4

What is the acrosome reaction?

Answer 4

• Exocytotic event involving fusion of plasma and acrosomal membranes
• It is triggered by binding to zona pellucida which stimulates an increase in intracellular Ca2+
• Hydrolytic enzymes are released to break down the zona pellucida

Question 5

What are the roles of ZP2 and ZP3?

Answer 5

• Glycoproteins found in the zona pellucida
• ZP3:
  
  • Binds to sperm with intact acrosome
  • It triggers an increase in intracellular Ca2+ which will start the acrosome reaction
• ZP2:
  
  • Binds to sperm with broken acrosome

Question 6

What are the two steps involved in activation of the egg?

Answer 6

• Cortical granule exocytosis
• Resumption of the cell cycle
  
  • NOTE: both triggered by Ca2+ release

Question 7

What is the process of cortical granule exocytosis?

Answer 7

• Wave of rapid depolarisation of zona pellucida
• Exocytosis of cortical granules as a result causes cleavage of ZP2 and modification of ZP3
  
  • This creates a polyspermy block as no other sperm can bind and undergo the acrosome reaction

Question 8

What is the process of cell cycle resumption? (6 steps)

Answer 8

1. Sperm enters oocyte cytoplasm
2. Phospholipase C zeta from sperm triggers increase in intracellular Ca2+
3. This causes activation of egg and resumption of meiosis II
4. Before fusing, the pronuclei of oocyte and sperm duplicate their DNA
5. Microtubules pull pronuclei together and membranes dissolve -> creates a zygote
6. Mitosis continues

Question 9

Detail what occurs on D12 after ovulation.

Answer 9

• Zygote’s metabolic needs met oviduct + endometrium secretions
• Endometrium is receptive for 3 days (coincides with max. levels of progesterone secretion by corpus luteum)
• Integrins on trophoblast allow it to attach to endometrium receptors
  
  • If endometrium is not mature enough, blastocyst moves to a lower level and tries to attach again

Question 10

What is the process of implantation?

Answer 10

1. Trophoblast with integrins attaches to endometrial receptors
2. Trophoblast proliferates and differentiates into cytotrophoblast (inner) and syncytiotrophoblast (outer)
3. Decidualisation response occurs - syncytiotrophoblast cells invade the endometrium until blastocyst is buried
4. Endometrial cells form a seal over the blastocyst
5. Trophoblast initiates changes in endometrium:
   
   1. Change in matrix composition
   2. Change in stromal cell morphology
   3. Sprouting + ingrowth of capillaries
6. Trophoblast cells release human chorionic gonadotropin (hCG) which stimulates continued production of progesterone and oestrogen until week 8

Question 11

What is the impact of a lack of hCG in implantation?

Answer 11

• Results in lack of oestrogen and progesterone which results in sloughing of the endometrium

Question 12

What is the source and role of hCG during pregnancy?

Answer 12

• From the blastocyst
• Maintains the corpus luteum

Question 13

What is the source and role of progesterone during pregnancy?

Answer 13

• From the corpus luteum and placental trophoblast
• Role:
  
  • Keeps myometrium + uterine muscle inactive
  • Promotes uterine growth (with oestrogen)
  • Relaxation of smooth muscle in genital, vascular, urinary and GI tracts
  • Initiate and maintain pregnancy (if levels drop, the pregnancy will fail)

NOTE: mifepristone is a progesterone receptor blocker used in abortions

Question 14

What is the source and role of oestrogen during pregnancy?

Answer 14

• From the corpus luteum and cooperation between foetal adrenal gland and liver, and the placenta
• Role:
  
  • For uterine growth and blood flow
  • Foetal adrenal makes 100-200mg/day (adult makes 20-30mg/day)

Question 15

What are the maternal adaptations during pregnancy?

Answer 15

• Metabolic:
  
  • Weight gain
  • Energy costs
  • Foetal weight doubles in last few months
  • Insulin resistance
• Hormonal:
  
  • Increase in serum oestrogens
• Cardiovascular:
  
  • Increase cardiac output and extracellular fluid volume
  • Decreased total peripheral resistance and plasma osmolarity
  • Mild anaemia
• Respiratory:
  
  • Increase ventilation and O2 consumption
  • Decreased pCO2 -> alkalosis
• Renal:
  
  • Increase renal flow and Na+ retention
• GI:
  
  • Increase nutrient and Ca uptake
  • Decreased gut motility

Question 16

What is the process of sex determination?

Answer 16

• SRY gene: found on Y chromosome, codes for SRY protein
  
  • SRY protein causes bipotential gonads to become testes
  • Lack of causes bipotential gonads to become ovaries
• Testosterone: produced by Leydig cells in males
  
  • Stimulates development of Wolffian duct to sperm tract
  • If it is not present, Wolffian duct degenerates
• Dihydrogen testosterone: converted from testosterone
  
  • If present, male genitalia develops
  • If not, female genitalia develops
• Antimullarian hormone: produced by Sertoli cells
  
  • Present in males, Mullarian duct degenerates
  • Not present in females, Mullarian duct forms
• Week 10:
  
  • Males: testes descend, cloaca forms penis, urethra and bladder
  • Females: mullarian duct forms fallopian tubes and uterus