Female Reproduction

Question 1

Describe the structure of the ovary:

Answer 1

• The ovary is surrounded by germinal epithelium (and a tunica albuginea)
• The inner medulla is heavily vascularised
• The outer cortex region is less well vascularised

Question 2

Describe the Embryonic Development of the Ovary:

Answer 2

1. The mesenophros surface epithelial cells in the area where the gonadal ridge region will form, change their phenotype into gonadal ridge epithelial like cells (GREL cells)
2. The GREL cells proliferate which forms the gonadal ridge and primordial ovary
3. The GREL cells continue to proliferate and the PGCs migrate into the developing ovary
4. The migrated PGCs proliferate as oogonia between the proliferating GREL cells
5. Stroma from the mesenophros then penetrates and expands into the developing ovary (with basal lamina at the leading edge)
   - Outside the basal lamina of the invading stroma are the PGCs and GREL cells and inside the basal lamina are the stromal cells and capillaries
6. The stroma continues to invade to the surface of the developing ovary and then spreads laterally- meaning surface GREL cells are underlaid by basal lamina
7. The GREL cells on the surface underlaid by the basal lamina transform into epithelium
8. The stroma invades into the ovigerous cords and breaks them up into smaller sections (of germ cells and GREL cells surrounded by basal lamina)
9. The first primordial follicles containing an oocyte and pre-granulosa cells form in the inner cortex-medulla region
10. In the final stage of development all of the ovigerous cords are divided into primordial follicles
11. The ovarian surface is now fully covered by surface epithelium underlaid by stroma which becomes the tunica albuginea

• In summary GREL cells that were trapped at the surface become the surface epithelial cells and GREL cells that were packaged with the oocytes become granulosa cells

Question 3

What is the origin of the oogonia?

Answer 3

• The primordial germ cells arise in the yolk sac and migrate through the wall of the developing gut, through the ventral mesentery and then laterally into the ovigerous cord
• Within the ovigerous cords the primordial germ cells develop into oogonia and eventually enter into meiosis and then arrest

Question 4

Describe the Process of Ooogenesis:

Answer 4

1. Primordial germ cells migrate to the gonadal ridges- when sex differentiation occurs they differentiate into oogonia and proliferate
2. Before birth the oogonium have proliferated via mitosis and become primary oocytes which arrest in prophase I
3. The primary oocytes remain arrested until puberty and meiosis only continues in the dominant Graafian follicle of each cycle- meiosis continues and then arrests in metaphase II with the formation of the secondary oocyte which occurs just prior to the follicle being ovulated
4. The secondary oocyte completes meiosis II just after fertilisation

Question 5

List the Phases of Follicular Development:

Answer 5

1. Primordial Follicles:
   - contains a primary oocyte surrounded by a layer of squamous granulosa cells
   - a pool of these cells is recruited to start development each ovarian cycle
2. Primary Follicles:
   - contains a primary oocyte
   - cuboidal granulosa cells start to surround the oocyte
3. Secondary Follicles:
   - contains a primary oocyte
   - there are now multiple layers of cuboidal granulosa cells
   - theca cells appear on the outside
   - In late secondary follicular development the antrum appears
4. Tertiary Follicles:
   - there is still a primary oocyte
   - contains a large fluid filled antrum
   - has multiple layers of granulosa cells
   - has a theca interna (secrete androgens) and theca externa layer (form a protective shell)
5. Graafian Follicles:
   - the oocyte is soon to become a secondary oocyte
   - the oocyte lies at the edge of the antrum in a mound of granulosa cells (called cumulus oophorous cells)
   - there is a very large fluid filled antrum
   - there is a large production of estrogen by the numerous granulosa cells
6. Pre-ovulatory follicles:
   - The oocyte recommences meiosis and becomes a secondary oocyte (suspended in metaphase II)

Question 6

How long does folliculogenesis take?

Answer 6

200-375 days

Question 7

How is the dominant follicle (Graafian follicle) selected?

Answer 7

• It is 2-5mm in size
• During the late luteal phase the selectable follicle responds to FSH and is the follicle that grows the most rapidly
• The dominant follicle then displays increases androgen production and enhanced aromatase activity

Question 8

Describe the maturation of the pre-ovulatory follicle:

Answer 8

• The follicle destined to ovulate enlarges to 18mm during the late follicular phase
• The follicle shows changes in steroidogenic activity (increases androgen production by theca cells and increases aromatase activity)
• The granulosa cells can now bind LH (which replaces FSH as the steroid hormone stimulus)
• The mid-cycle LH surge causes the follicle to switch to progestin production which is needed for ovulation

Question 9

Describe the Process of Ovulation:

Answer 9

• The pre-ovulatory LH surge (triggered by increasing estrogen levels produced by the maturing follicles) triggers a number of events in the ovary (in particular in the dominant follicle:
  1. Cumulus expansion in the dominant follicle
  2. Protein synthesis changes in and around the follicle including production of collagenase to break down the follicular wall
  3. Increased blood flow to the ovary and follicle which increases follicular pressure

Question 10

Describe the Formation of the Corpus Luteum:

Answer 10

1. After ovulation the remnants of the ovulated follicle form the corpus haemoohagicum
2. This is remodelled into the corpus luteum by: granulosa cell hypertrophy, becoming vascularised, lipid accumulation and significantly increased progesterone production
3. The granulosa cells become granulosa lutein cells which under the influence of LH produce progesterone as StAR is now expressed in these cells
4. If pregnancy occurs hCG will be produced to maintain the corpus luteum but it no fertilisation occurs the corpus luteum will be degraded into the corpus albicans (white body)

Question 11

Describe the changes in sex steroid hormone production during changes in folliculogenesis:

Answer 11

1. Recruitment of primordial follicles into primary and then pre-antral (secondary) follicles is spontaneous (GnRH independent)
2. In order for secondary follicles to develop into tertiary follicles FSH is needed
3. Within the pre-ovulatory follicle there is an increase in estradiol production and a decrease in FSH levels (as well as the acquisition of LH receptors)
4. The high levels of estradiol produced by the pre-ovulatory follicle triggers the LH surge which triggers ovulation
5. The corpus luteum then produces progesterone

Question 12

Describe the Menstrual (Uterine) Cycle:

Answer 12

• The menstrual cycle is driven by the steroid hormones released by the ovary

Day 1-5: Menstrual phase:

• shedding of the functional layer of the endometrium
• Estrogen and progesterone are low

Day 6-14: Proliferative (pre-ovulatory) phase:

• rebuilding of the functional layer of the endometrium and proliferation of glandular epithelial cells, stroma and blood vessels
• cervical mucous becomes less viscous and sticky
• This phase is driven by estrogens

Day 15-28: Secretory (post-ovulatory) phase:

• begins immediately after ovulation
• endometrium prepares for implantation as glands enlarge, arteries elongate and glycogen is secreted
• This phase requires progesterone and estrogen from the corpus luteum

Question 13

Describe how estrogen is synthesised in the ovary:

Answer 13

• The major site of estradiol production is in the developing Grafian follicle
  1. LH acts on Theca cells and triggers the synthesis of testosterone
  2. The testosterone diffuses into the granulosa cells which under the stimulation of FSH produce aromatase enzyme which converts testosterone into estradiol

Question 14

Describe feedback on the HPG axis in the female reproductive system:

Answer 14

1. Estrogen: positive and negative feedback at the level of pituitary and hypothalamus
2. Progesterone: negative feedback at the level of the pituitary and the hypothalamus
3. Inhibin: negative feedback at the level of the pituitary inhibiting secretion of FSH

Question 15

Describe the function of inhibin A and inhibin B:

Answer 15

• Inhibin A and B are produced by the granulosa cells of the ovary
• Inhibin A and B are produced in developing follicles and the dominant (Graafian) follicle
• Inhibin A is elevated in the luteal phase of the cycle
• Inhibin B is elevated in the midfollicular phase (when there are the most developing follicles)
• The inhibins cause inhibition of FSH secretion (inhibin B is most effective)

Question 16

What is the role of estrogen in the female body?

Answer 16

• Promotes oogenesis
• Increases growth of female reproductive organs
• Contributes to cardiac, bone and mental health
• With progesterone they regulate the menstrual cycle and alter cervical mucous