Lecture 12: Human Development 1 & 2

Question 1

Name the two periods of embryology and which weeks each spans.

Answer 1

Embryology

1. Embryonic period: weeks 1-8
2. Fetal period: weeks 9-38

Question 2

What happens during the fetal period? When is it?

Answer 2

Fetal period: weeks 9-38 differentiation, development, super-specialized cells, fetal growth

Question 3

What happens during gastrulation? Which week is it?

Answer 3

Gastrulation: 3 germ layers form – “most important day of your life” (Week 3)

Question 4

Birth defects

1. What two diseases/drugs contributed to specific understanding of embryonic/fetal growth?
2. What are their clinical features?
3. How does one prevent against the above defects in each case?
4. One of them is used for experimental treatment in other indications. Name them!

Answer 4

1. thalidomide (anti-emetic drug for pregnant women) and Rubella (German measles) 2. Defects/missing: limbs (arms), ear, hips, thumb, etc. 3. thalidomide - don’t give it to pregnant women; Rubella vaccine 4. thalidomide: as potential Tx: antiangiogenesis drug for cancer (ex. Karposzy’s sarcoma, angiomas of the eye/throat of infants)

Question 5

Birth defects - Advanced maternal age

1. At what age range do older women carry a higher risk for birth defects?
2. What is the cause of these defects?
3. what is oocyte atresia?
4. Name diseases that carry a higher risk with AMA
5. What is a modern method to potentially help against AMA-derived birth defects in women?
6. If a menopausal or infertile woman wanted to have a child, how could she do this?

Answer 5

1. AMA ~ congenital defects / infertility: age 35+
2. mid-30’s onwards → loss of DNA fidelity → more translocations → congenital defects/infertility
3. age-dependent loss of oocytes / oocyte atresia (a type of apoptosis) (early menopause)
4. autism, Down syndrome
5. frozen eggs are great
6. menopause onset/infertility: lack of viable oocytes (→ mature → 2o oocytes → ovulation) o Tx: adopt or egg donor IVF

Question 6

Fertilization issues

1. chromosomal nondisjunction: explain the differences between complete and mosaic cases.

Answer 6

If very early (Complete): almost every cell has a defect, generally not compatible with life Mosaic: defect later in development, not as severe

Question 7

Fertilization issues

* What are trisomy and triploidy? Give examples of each.

Answer 7

Trisomy - 3 chromosomes on specified number * Down Syndrome (Trisomy of Chromosome 21) * Trisomy 13 Triploidy (polyspermy)

Question 8

Angelman Syndrome and Prader-Willi Syndrome

* Which chromosomal defect does each have?

* What physical/behavioral/developmental features do they have in common?

* What features does each have?

Answer 8

Both are chromosome 15 deletions

Question 9

spontaneous abortion (SAB)

1. What are the 3 kinds of chromosomal abnormalities associated with spontaneous abortion?
2. Name 3 other potential causes of SAB.
3. From approximately what age onwards is AMA a factor? Why? Which diseases may result in higher frequences with AMA?
4. Name a standard treatment for frequent unexplained SAB.
5. What else can be done to avoid AMA-associated risks?
6. What is oocyte atresia?

Answer 9

SAB

1. major cause: chromosomal abnormalities: deletions, translocations, nondisjunction
2. other causes

• cleavage abnormalities
• insufficient progesterone
• AMA

3. AMA ~ congenital defects / infertility: age 35+

• mid-30’s onwards ~ fidelity issues ~ more translocations ~ congenital defects/infertility
• ex. autism, Down syndrome
• frozen eggs are great

4. progesterone

5. menopause onset/infertility: lack of viable oocytes (that mature 2^o oocytes and can ovulate)

• Tx: adopt or egg donor IVF
  6. age-dependent loss of oocytes / oocyte atresia (early menopause) (a type of apoptosis)

Question 10

1. Which cells are haploid? Diploid? How many chromosomes does each have? Why are haploid cells haploid? Why are Diploid cells diploid?
2. What is gameotogenesis? When does gametogenesis occur?
3. Gametogenesis in females:

* When does it begin?

* When does it end?

* How many oocytes are in 5 mo. olds? Menarche? Menopause? How many oocytes are consumed each menstrual cycle?

* How does one calculate the number of eggs that complete gametogenesis?

4. Gametogenesis in males:

* When does it begin?

* When does it end?

* What is the peak interval for maximum sperm production?

Answer 10

1. Gametes: specialized haploid (n) (23 chromosomes) (due to meiosis) female/male germ cells

Somatic cells: diploid (2n, 46 chromosomes); non-gametes

2. Gametogenesis: formation of gametes

• much earlier than meiosis
• even before gonad differentiation (in embryonic development)

3. females:

• begins: several months before birth
  
  • most oocytes in ovary arrested in prophase of Meiosis I (primary oocyte)
• only a few thousand oocytes complete meiosis I and enter meiosis II (rapid) (secondary oocyte)
• 6-7 million oocytes in 5 mo. old
• Selection process (not random)
• declining number, until start of menses (menarche) (2-4k oocytes)
• @ 10/menstrual cycle over average 40 year span
• ends: fertilization
  
  • only a handful of oocytes are fertilized and complete gametogenesis = mature gametes)
  • # eggs that complete gametogenesis ~ 2x # live children (~1/2 miscarriages/SAB)
  • menopause (late 40’s-50’s): no more viable oocytes
• maturity of eggs: @ fertilization
• assume ½ SAB (# kids * 2 = oocytes to completion)
• overall: >99.9% of oocyte decline due to oocyte atresia (apoptosis); <0.01% are ovulated

4. males: sperm donor ~ every 3 days (max. amt.)

• begins: after onset of puberty
• ends: death

Question 11

1. Normally, how many sperm are there per mL?
2. What is the volume of ejaculate and total number of sperm per ejaculate?
3. What counts are associated with infertility?
4. Explain two ways the sperm works to contact the oocyte.
5. How much work does the sperm put in versus the oocyte? Explain.
   6a. True or False: Sperm are/aren’t pH sensitive.
   6b. The cervical canal is (acidic/basic).
   6c. The uterus is (acidic/basic)
6. Where does sperm originate?
7. Where is the sperm’s destination? How many arrive? How is one sperm selected among the many?

Answer 11

2. ejaculate is 2-6 ml (200-600 million sperm)
3. Counts <10 million/ml are associated with infertility
4. 2 methods sperm undertake to contact the egg

• In the female reproductive tract, muscular contractions are stimulated by prostaglandins in the semen.
• Sperm swim 2-3 mm/minute, varying with pH.

5. Sperm: 1/3; oocyte 2/3
6. Sperm are pH sensitive (slower in acidic environments, faster in alkaline environments).

Cervical canal (acidic): slow sperm travel

Uterus (basic): fast sperm travel

7. Sperm are produced in the seminiferous tubules of the testes.
8. Only about 200 sperm arrive in the ampulla. Some swim in the wrong direction. The fastest sperm is selected; the rest are absorbed.

Question 12

1. What is sperm capacitation? Why is it important? How long does it take?
2. Capacitated sperm are (more/less active) and (can/cannot) undergo the acrosome reaction.
3. What procedure is necessary during IVF to substitute for capacitation?

Answer 12

1.

• Freshly ejaculated sperm are unable to fertilize and require capacitation, a process requiring 6-8 hours.
• The glycoprotein coat and seminal proteins are removed from the acrosome surface.

2. Capacitated sperm are more active and can undergo the acrosome reaction
3. IVF: thorough washing of sperm mimicks capacitation (or else the sperm is not active)

Question 13

Acrosome Reaction

1. The acrosome reaction occurs (before/after) capacitation.
2. What happens during the acrosome reaction (5 steps)? What is speciation and how does it play a role in this process?

Answer 13

1. The acrosome reaction can only occur after capacitation occurs.
2. The five steps of the acrosome reaction are as follows.

• The ZP3 receptor (a zona pellucida glycoprotein) is the primary sperm receptor that induces the acrosome reaction. 
• When sperm contact the follicular cells, they release hyaluronidase
• the acrosome membrane perforates (disintegrates) due to the action of angiotensin converting enzyme (ACE) in the acrosome
  
  • Sperm have ZP3 receptors which bind oocyte ZP3
    
    • speciation; different species cannot mate because they have different receptors/proteins
  • ACE: The same blood pressure regulator; drug for high BP (middle-aged white males)
• This causes release of enzymes that break down the matrix and permit sperm penetration through the follicular cells and the zona pellucida.