70 Oogenesis and follicular development

Question 1

What makes up the fundamental female reproductive unit?

Answer 1

Single ovarian follicle, composed of one germ cell (oocyte), surrounded by endocrine cells

Question 2

What is menarche?

Answer 2

• Beginning of menstrual cycles

* Average: 11-13 y

Question 3

What determines age at puberty?

Answer 3

• Genetics
• Nutrition
• Geographic location
• Exposure to light
• Body composition, fat deposition
• Exercise

Question 4

What controls the menstrual cycle?

Answer 4

Gonadotrophins and gonadal hormones

Question 5

What are the 3 phases of the ovarian cycle?

Answer 5

1. Follicular phase:
   • Av. 15 days (range 9-23 days)
2. Ovulatory phase:
   • 1-3 days (and culminates with ovulation)
3. Luteal phase:
   • 13 days - (is less variable than follicular)

Question 6

What are the 3 phases in endometrial cycle?

Answer 6

1. Menstruation
2. Proliferative
3. Secretory

Question 7

What are 4 ovarian functions?

Answer 7

1. OOGENESIS - production of gametes during the foetal period
2. MATURATION of oocyte
3. EXPULSION of the mature oocyte (ovulation)
4. SECRETION of female sex steroid hormones (oestrogen + progesterone) and peptide hormone inhibin

Question 8

Development of oocyte and ovarian follicle?

Answer 8

1. Primordial follicle:
   • Oocyte
   • Granulosa cells
2. Primary follicle:
   • Fully grown oocyte
   • Zona pellucida
3. Prenatal follicle:
   • Early theca
4. Early antral follicle:
   • Fluid in antrum
   • Theca
5. Mature follicle: (1.5cm):
   • Cumulus oophorous

Question 9

What is oogenesis?

Answer 9

• Steps/ process a developing egg (oocyte) goes through to differentiate into a mature egg (ovum)
• Involves completion of meiosis which occurs at the time of fertilisation

Question 10

Progression of oogonia to primordial follicle?

Answer 10

• Oogonia produced by mitotic division (max # ~ 7 million)
• 8-10 wks of gestation, prophase of 1st meiosis stars - becomes primary oocyte
• Surrounded by pre-granulosa cells: called primordial follicle

Question 11

What is mitosis?

Answer 11

Process of cell division that results in 2 genetically identical daughter cells developing from a single parent cell

Question 12

What is meiosis?

Answer 12

• Division of a germ cell involving 2 fissions of the nucleus and giving rise to 4 gametes, or sex cells, each possessing 1/2 the no. of chromosome of the OG cell

Question 13

Describe the 1st phase of oogenesis that occurs during foetal life?

Answer 13

1. Oogonia develop in the embryonic yolk sac 3 weeks post conception
2. Migrate to ovary
3. Colonise the cortex
4. Undergo mitosis
5. At 8-10 weeks meiosis begins
6. Millions of oocytes degenerate before birth:
   • 1-2 million around birth
   • 400,000 around puberty
7. Remaining oocytes are arrested in meiotic prophase until last oocytes are ovulates (up to ~ 50 years)

Question 14

Rate of cytogenetic abnormalities increases with maternal age. What are 2 common cytogenetic abnormalities?

Answer 14

1. Aneuploidy

2. Down Syndrome

Question 15

Describe the 2nd phase of oogenesis at ovulation?

Answer 15

Meiosis resumes (stimulated by LH):
• 1st division of meiosis is completed and the haploid nuclei separate to form 2 cells
• Cytoplasm is unequally shared forming - a large secondary oocyte and a polar body (PB has no further role)
• Meiosis arrests again at metaphase II and the secondary oocyte is ovulated
• 2nd division of meiosis is only completed in those oocytes that are fertilised

Question 16

Oocytes summary?

Answer 16

Female germ cells:
• 1 st observed in the embryonic yolk sac
• Then migrate to developing ovaries
• Proliferate
• Reach max. numbers before birth

Question 17

Spermatogenesis vs oogenesis?

Answer 17

1. Proliferation:
   • Females - mitotic proliferation of oogonia occurs prior birth
   • Males - spermatogonia proliferate only after puberty
2. Meiotic divisions:
   • Females - meiotic divisions of oocyte produces only 1 mature ovum
   • Males - meiotic divisions of primary spermatocyte produces 4 mature spermatozoa
3. Second meiotic division:
   • Females - 2nd meiotic division only completed upon fertilisation
   • Males - products of meiosis (spermatids) undergo substantial differentiation in the maturing process

Question 18

Female - Oogenesis:
• Continuous?
• Temp?
• Begins?
• Stem cells?
• Mobile gametes?

Answer 18

• Discontinuous (periods of arrest)
• Normal body temp
• Meiosis begins before birth (initial stimulus is not steroidal)
• Results in finite numbers of oocytes (ovary has no stem cells)
• Results in immobile gametes

Question 19

Spermatogenesis:
• Continuous?
• Temp?
• Begins?
• Stem cells?
• Mobile gametes?

Answer 19

• Continuous
• Lower temp required
• Meiosis begins at puberty (indirectly dependent on progesterone)
• Results in infinite numbers of sperm (testis has a stem cell population)
• Results in motile gametes

Question 20

What are follicles?

Answer 20

Eggs exist in ovaries in structures known as follicles

Question 21

Follicle development?

Answer 21

1. Primordial follicle = single layer of granulosa cells around oocyte
2. Oocyte size increases, multiple layers of granulosa cells + separation of oocyte from granulosa cells by thick layer of material (zona pellucida)
3. BUT cytoplasmic processes cross the zona pellucida and form gap junctions with oocyte and nutrients and chemical messengers are passed to oocyte
4. Follicle grows by mitosis of granulosa cells and some differentiate to become theca
5. Antrum begins to form from amongst granulosa cells from fluid they secrete

Question 22

Features of small follicles (primordial)

Answer 22

• Most numerous follicles at any time
• Non-growing (stock pile)
• Oogonium nucleus
• Single layer of follicular cells (granulosa cells)

Question 23

What hormone is secreted by primordial follicles?

Use?

Answer 23

• Secrete anti-Müllerian hormone (AMH)

* Levels reflect the ovarian follicular reserve and therefore can be measure to assess ovarian ageing

Question 24

Medium follicles (primary)
• At puberty she has ≈ _____ oocytes
• She may experience ___ cycles
• She loses approx. ___ per cycle

Answer 24

• At puberty she has ≈ 300,000 oocytes
• She may experience 450 cycles
• She loses approx. 650 per cycle

Question 25

What are the stages of medium follicle (primary) development?

Answer 25

* Throughout life, cohorts of small follicles recruited to gain a period of slow growth * Follicular (granulosa) cells divide, forming 3 layers around the oocyte * Growth is independent of hormones * Takes 85 days (3 cycles) to reach 3 layers of follicular cells

Question 26

Other names for large follicles?

Answer 26

* Secondary * Antral * Graafian * Preovulatory

Question 27

Stages of development of large follicles?

Answer 27

1. FSH stimulates rapid development of medium follicles over 14 days: leads to either ovulation or atresia • Zona pellucida develops and enclosing the oocyte and masking its antigens • Rapid mitotic division in follicular cells forms many layers • Antrum develops and fills with fluid 2. LH activates the theca internal to synthesis androstenedione- precursor for estradiol 17-β synthesis by granulosa cells

Question 28

* Initial growth is _________ of hormones and takes ___ days * Final growth is _________ on FSH and takes ______ days

Answer 28

* Initial growth is independent of hormones and takes 85 days * Final growth is dependent on FSH and takes 10-14 days

Question 29

Process of corpus luteum formation?

Answer 29

1. Mature follicle discharges its antral fluid and egg • Collapses around antrum and undergoes rapid transformation 2. Granulosa cells enlarge and form gland-like structure - CORPUS LUTEUM 3. Corpus luteum secretes: • Oestrogen, progesterone, inhibit 4. If no egg fertilisation, CL developments reaches max. within ~ 10 days: • Rapidly degenerates by apoptosis

Question 30

What does corpus luteum secrete?

Answer 30

* Oestrogen * Progesterone * Inhibin

Question 31

What happens in follicular phase (Days 1-14)?

Answer 31

``` Bleeding starts (Day 1): • Uterine bleeding (Days 1-5/6) • Multiple follicles develop (Days 1-7) • One follicle becomes dominant (Day 7) • Dominant follicle matures (Days 7-14) ```

Question 32

What happens in luteal phase (Days 14-28)

Answer 32

``` Ovulation starts (Day 14): • Corpus luteum functions (Days 14-25) • Corpus luteum degenerates (Days 25-28) ```