Ovulation and spermatogenesis

Question 1

B1*

Describe meiosis

Answer 1

• Cell division necessary for sexual reproduction to produce haploid gametes → these can then fuse together to form diploid zygotes
• 2 rounds of division that result in 4 cells with only one copy of each paternal and maternal chromosome (haploid)
• Prior to meiosis, DNA replication occurs - each chromosome now has 2 copies known as sister chromatids (attached at centromere)
• Meiosis I: diploid cell with 2 copies of each chromosome (maternal and paternal homologous chromosomes) undergoes reduction division to give 2 haploid daughter cells with one chromosome from each pair
• Genetic recombination: homologous chromosomes pair up and exchange genetic material via crossing over in prophase I
• Meiosis II: each chromosome splits into separate sister chromatids
• Results in 4 genetically distinct cells produced (gametes with 23X or 23Y)

Question 2

Describe the egg

Answer 2

• Ova/eggs formed 14-20 weeks foetal life
  
  • 7 million at 20 weeks
  • 2 million at birth
  • 300 000 at menarche
  • 0 at menopause
• Lack of Y chromosome results in formation of ovaries
• Eggs can be destroyed e.g. by autoimmune disease or toxins such as chemotherapy

Question 3

Descrieb oogenesis

Answer 3

• Begins before birth and completes after puberty
• Oogonia: primordial germ cells that proliferate by mitosis to generate ~7 million by 20 weeks gestation
• Cell death results in ~2 million cells
• Primary oocyte: oogonia enlarge and begin meiosis I but arrest in prophase I until reproductive cycles begin at puberty (no 1° oocytes form after birth)
• Primordial follicle: primary oocyte surrounded by layer of flattened follicular cells
• Primary follicle: at puberty, primary oocyte enlarges and follicular cells plump up to columnar cells
• Secondary oocyte: 36-38 hours before ovulation (day 14/28), LH surge causes 1° oocyte to complete meiosis I
• 15-20 primary oocytes mature each month, but only 1 reaches full maturation to become an oocyte
• Polar body produced with much less cytoplasm (discards extra haploid set of chromosomes)
• Ovulation: second meiotic division begins and stops at metaphase II
• Mature oocyte: at fertilisation, second meiotic division completes forming a 23X gamete
• Second polar body formed

Question 4

Recall the role of hypothalamus in ovulation

Answer 4

• Hypothalamus at base of brain produces Gonadotropin Releasing Hormone (GnRH)
• GnRH secreted into special veins that connect to pituitary gland
• Pulsatile secretion 60-90 minutes from the beginning of cycle to ovulation
• Pituitary produces Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH) - targeted to granulosa and theca cells respectively, producing inhibin and oestrogen, and androgens, respectively
  
  • FSH keeps follicles growing
  • LH is a trigger hormone to develop a pre-ovulatory follicle and to ovulate it
    
    • LH surge lasts ~36 hours

Question 5

Describe the ovarian cycle

Answer 5

1. Follicular phase: day 1 menstruation → ovulation
   * Primordial follicles grow over 8 months before cycle starts
   
   • Number of follicles recruited depends on numbers remaining
     * Follicle grows and produces fluid, forming antral space
     * One follicle becomes the dominant follicle and others shrivel up
     * Primary follicle: 1° oocyte surrounded by Theca and
     granulosa cells
   • Theca cells: bind LH and secrete androstenedione
   • Granulosa cells: binds FSH and produce aromatase to convert androstenedione to estradiol
     * Increased oestrogen serves as –ve feedback to pituitary (↓ FSH release)
   • Without FSH, some follicles die off
     
     • Dominant (Graafian) follicle continues to grow
2. Ovulation:
   * Oestrogen levels peak toward end of follicular phase, stimulating anterior pituitary (+ve feedback)
   * Growing follicle is ~20mm size
   * LH/FSH surge
   
   • Follicle releases proteolytic enzymes that degrade follicular tissue
   • ~36 hours after surge, 2° oocyte leaves ruptured follicle
3. Luteal phase (~14 days)
   * Follicle folds inward on itself, forming corpus luteum
   * Produces oestrogen and progesterone
   
   • Proliferation of endometrium
   • Inhibit FSH/LH secretion so no new follicles develop

• Oestrogen levels throughout cycle:
  
  • 100 on day 1
  • 300 on day 5
  • 600-700 on day 10
  • 1000 day 14

Question 6

describe sperm

Answer 6

• 55 microns long - 5 micron head and 50 micron tail
• Live 3-4 days in female
• Move 2mm/ min - assisted by uterine contraction & fallopian tube cilia
• Spermatogenesis requires compaction of DNA in nucleus - many cross-links make DNA more stable and stop fragmentation
• Organisation of chromatin (DNA, protein and RNA) for packaging involves:
  * Chromosome anchoring - attachment of DNA to nuclear annulus
  * Formation loop domains
  * Replacement of histones by protamines condensing DNA into compact doughnuts
  * Chromosomal positioning
• Epididymal maturation involves protamine cross-linking by disulphide bond formation

Question 7

Describe spermatogenesis

Answer 7

• Testosterone in foetus develops male sex glands and ducts → testes begin to function in foetal life
  secreting testosterone
• Mature sperm not made until puberty → occurs in tubule of testis - tubule contains developing sperm
  at all stages along length
  
  • 200-300 tubules per testis (highly convoluted)
  • Tales 48 days for sperm to form - spermatogenesis processes continuous
• Hypothalamus signals anterior pituitary via GnRH to produce LH and FSH
  
  • LH stimulates Leydig cells to produce testosterone
  • FSH stimulates Sertoli cells, which help produce sperm
• Spermatogonia: initial pool of diploid cells (46XY) that divide by mitosis into 2 daughter cells
  
  • Type A: continually undergo mitosis to replenish spermatogonia pool
  • Type B: primary spermatocytes that later form mature sperm
• Primary spermatocytes (46XY) - don’t further differentiate until puberty
  
  • Meiosis I: 2 haploid (23 X or Y) → 2° spermatocytes (homologous chromosomes separated)
  • Meiosis II: 4 haploid (23 X or Y) spermatids (sister chromatids separated)
• Spermiation: sperm released into seminiferous tubule lumen
• Spermiogenesis: spermatids differentiate into spermatozoa
  
  • Flagellum forms for motility
  • Midpiece thickens with mitochondria to ensure energy supply
  • Acrosome forms where enzymes are stored to penetrate the zona pellucida
  • DNA becomes tightly condensed
• Spermatozoa travel through seminiferous tubules to epididymis where they gain motility → motile for
  ~2 weeks
• Epididymis connects to vas deferens - takes sperm out of scrotum to male accessory glands
  
  • Accessory glands: seminal vesicles, prostate gland (form fluids with sperm to form semen)

Question 8

Describe fertilisation

Answer 8

• Millions of sperm deposited in the vagina during sex
  
  • 200 reach fallopian tube
  • 10 in ampulla at time of fertilisation
• Fertilisation needs to be within 10 hours for ovulation, so best for sperm to be waiting
• Capacitation: taking the brakes off the sperm’s swimming speed and increasing head stickiness
• Ovulated egg has jelly-like cumulus that sperm swim through and tough glassy zona pellucida which sperm must attach to
  
  • Acrosome in sperm head is full of digestive enzymes - released when sperm attaches to zona and eats through
• Contact with cell membrane → sperm fuses
• Electrical signal causes egg to secrete cortical granules of mucus to smother the egg membrane and prevent more sperm from entering (15 seconds)
  
  • If 2 sperm enter at same time, can cause polyploidy (69 chromosomes)
• Sperm head inside the egg disintegrates, revealing 23 chromosomes
• Egg completes its 2nd meiotic division to form 23 chromosomes
  
  • 2 pronuclei = sign of fertilisation in 16-20 hours
• Pronuclei fuse chromosomes → 46 XX or 46 XY
• Fertilised egg divides several times without increasing in size until 16 cells, then bind strongly to each other to form a morula
• Enters uterine cavity 3 days after ovulation and fertilisation
• Develops fluid-filled cavity becoming a blastocyst
  
  • Trophoblast: outer rim of cells will become the placenta
  • Embryoblast: inner ball will become the foetus