LECTURE 26 - ovarian function

Question 1

What are the 3 waves of ingressing cells that lead to gonad development?

Answer 1

1. Primordial germ cells (PGCs) - form gametes
2. Coelomic (germinal) epithelium - sex cords (granulosa cells)
3. Mesonephric cells - blood vessels (& theca cells)

Question 2

When happens to Primordial germ cells in the first 7 weeks?

Answer 2

• first visible at ~3 weeks in epithelium of yolk sac (neat base of allantois)
• expand by mitosis and migrate to genital ridges weeks 3-7
• remain ‘indifferent’ until ~weeks 6-7

Question 3

What are the female reproductive organs?

Answer 3

• uterus
• vagina
• cervix
• fallopian tubes: connect ovaries but don’t physically connect
• ovaries: lie laterally and attach to walls of peritoneal cavity

Question 4

What are the 2 main functions of the ovary?

Answer 4

1. produce oocytes

2. produce hormones

Question 5

How are oocytes formed?

Answer 5

Oogonia
- mitosis
- completion of last pre-mitotic division –> oocytes
- enter meiosis:
- primary oocytes - 1st mitotic division (arrest at prophase I)
only enters 2nd mitotic division if ovulation occurs
- secondary oocytes - 2nd mitotic division (arrest at metaphase II)
oocyte only undergoes full mitosis if fertilised

Question 6

What is meiosis and how does it occur?

Answer 6

maintains genetic diversity
Meiosis I
- synapsis: pairing of homologous chromosomes (2N 4C) => bivalent (or tetrad)
- crossing over (chiasmata)
- separation of maternal and paternal chromosomes = 2^23 (8,338,604 combinations)
- chromatids do not separate (1N 2C)

Meiosis II
- separation of chromatid pairs (1N 1C)

Question 7

What are polar bodies and how do they form?

Answer 7

• by-products of meiotic division: get discarded by the oocyte
• oocyte mitotic division is asymmetrical and results in formation of polar bodies
• polar body is a way of getting rid of XS DNA, may or may not divide
• contains little cytoplasm

Question 8

What are the follicular cells?

Answer 8

2 main types of somatic cells:

1. Granulosa cells: epithelial - produced oestrogens & progestagens
2. Theca cells: stromal/ interstitial - produce androgens & progestagens

Question 9

What is folliculogenesis?

Answer 9

Primordial follicle
- primary oocyte surrounded by a single layer of flattened granulosa cells

Puberty

• a few primordial follicles begins to mature each day - hormone-independent
• oocyte starts to grow and produce proteins needed for maturation and development post fertilisation
• at puberty HPG axis turned on, follicles start to develop when FSH and LH released

Question 10

What is atresia?

Answer 10

The degeneration and resorption of follicles before they have reached maturity

• very few oocytes/ follicles survive to ovulation
• vast majority eliminated before brith
• earliest signs of apoptosis in Graafian follicles are:
• condensation (pyknosis) and fragmentation of chromosomes and wrinkling of the nuclei envelope of oocyte
• pykonsis of granulosa cell nuclei, detachment of membrana propria - granulosa cells - free-floating in the follicular fluid

Question 11

What do primary (pre-antral) follicles look like?

Answer 11

• oocyte in middle
• region called zone pellucida around the outside
• granulosa becomes cuboidal
• theca and ZP become visible

Question 12

How does the zone pellucida (ZP) form?

Answer 12

• produced by oocyte
• glycoprotein layer - present around all mammalian eggs; 4 ZP proteins in humans
• islands of materials produced by the oocyte appear between adjacent granulosa cells and fuse together
• granulosa cells processes transverse ZP and contact oocyte - essential for egg nutrition
• following ovulation, ZP remains surrounded by cumulus cell (corona radiata) - important role in sperm interaction/ fertilisation and protection of early embryo

Question 13

What do secondary (early antral) follicles look like?

Answer 13

• granulosa cells proliferate - become 3-6 layers deep; secrete follicular fluid
• granulosa cells express FSH receptors and can be picked up
• theca forms 2 distinct layers - interna and externa; 10-15 secondary follicles rescued per cycle

Question 14

What does a tertiary (pre-ovulatory) follicle look like?

Answer 14

• granulosa cells continue to secrete follicular fluid
• oocyte surrounded by granulosa cells attached by the cumulus oophorous (egg stalk)
• 1 dominant follicle selected per cycle

Question 15

Describe the extra-ovarian hormone action

Answer 15

Hypothalamus 
GnRH - pulsatile release
--> 
Anterior pit. - gonadotrophins 
FSH
- acts on ovary
- stimulates follicle development 

LH

• acts on ovary
• stimulates follicle maturation and development of the corpus luteum

FSH+LH
- stimulate secretion of oestradiol and ovulation

Question 16

What are the ovarian hormones?

Answer 16

Oestrogens (17B oestradiol)
- growth of body and sex organs at puberty
- development of secondary sexual characteristics
Reproduction
- follicle maturation
- preparation of the endometrium for pregnancy
- thinning of cervical mucus

Progesterones

• uterus: completes the preparation of endometrium for pregnancy
• breasts: stimulates the development of mammary glands

Question 17

What are the phases of the menstrual cycle?

Answer 17

Oocyte maturation and endometrial growth 
Follicular phase 
- follicles mature 
- endometrium proliferates
- oocyte released 

Luteal phase

• corpus luteum
• endometrium prepared for blastocyst implantation

Menses if no pregnancy

Question 18

What happens in the follicular phase?

Answer 18

• hypothalamus: pulsatile GnRH release
  –>
  anterior pituitary secretes FSH (acts on granulosa cells) & LH (acts on theca cells)
  –>
  up to 15 follicles are rescued by FSH and start to mature

Question 19

What is the ‘two-cell hypothesis’ of oestrogen production?

Answer 19

• LH stimulates theca cells to produce androgens
• FSH stimulates granulosa cells (aromatase) to convert androgen to oestrogen (thickens endometrium/ thins cervical mucus)
• oestrogen suppresses FSH and LH production by ant. pit.

Question 20

How is ovulation stimulated?

Answer 20

Switch to +ve feedback
dominant follicle has highest FSH receptor density
–>
granulosa cells in the dominant follicle express LH receptors
–>
high levels of oestrogen at mid cycle stimulate the hypothalamus to release GnRH - +ve feedback
–>
causes LH surge and FSH spike from ant. pit.

Question 21

What is ovulation?

Answer 21

Changes in the follicles 
- increase in number of granulosa cells and accumulation of follicular fluid 
- cumulus oophorus loosens 
- follicle wall weakens 
- protease produced 
- increased osmotic pressure 
- stigma forms 
--> ovulation 
LH and FSH levels fall

Question 22

What happens in the luteal phase?

Answer 22

• formation of the corpus luteum is stimulated by the LH surge
• fibrin clot forms in ruptured follicle
  Granulosa cells –> large lutein cells
  Theca internal cells –> small lutein cells
  (Luteinization)
• LH maintains the corpus luteum
• LH (+FSH) stimulates progesterone and oestrogen production
  –>
  increased oestrogen and progesterone maintains endometrium
  –>
  limits new follicular development

Question 23

What is luteolysis?

Answer 23

• occurs ~12 days post ovulation
• if there is no human chorionic gonadotrophin (hCG) secreted by implanting blastocyst, corpus luteum degenerates forming corpus albicans
• progesterone and oestrogen levels fall –> removes -ve feedback –> cycle recommences

Question 24

What happens in pregnancy?

Answer 24

• if pregnancy occurs, developing embryo (blastocyst) produces hCG - acts like LH to maintain the corpus luteum
• corpus luteum continues to produce progesterone to support pregnancy and support ovulation
• at 6-7 weeks the placenta takes over production of progesterone