LECTURE 26 - ovarian function Flashcards
What are the 3 waves of ingressing cells that lead to gonad development?
- Primordial germ cells (PGCs) - form gametes
- Coelomic (germinal) epithelium - sex cords (granulosa cells)
- Mesonephric cells - blood vessels (& theca cells)
When happens to Primordial germ cells in the first 7 weeks?
- 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
What are the female reproductive organs?
- uterus
- vagina
- cervix
- fallopian tubes: connect ovaries but don’t physically connect
- ovaries: lie laterally and attach to walls of peritoneal cavity
What are the 2 main functions of the ovary?
- produce oocytes
2. produce hormones
How are oocytes formed?
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
What is meiosis and how does it occur?
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)
What are polar bodies and how do they form?
- 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
What are the follicular cells?
2 main types of somatic cells:
- Granulosa cells: epithelial - produced oestrogens & progestagens
- Theca cells: stromal/ interstitial - produce androgens & progestagens
What is folliculogenesis?
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
What is atresia?
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
What do primary (pre-antral) follicles look like?
- oocyte in middle
- region called zone pellucida around the outside
- granulosa becomes cuboidal
- theca and ZP become visible
How does the zone pellucida (ZP) form?
- 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
What do secondary (early antral) follicles look like?
- 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
What does a tertiary (pre-ovulatory) follicle look like?
- 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
Describe the extra-ovarian hormone action
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
What are the ovarian hormones?
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
What are the phases of the menstrual cycle?
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
What happens in the follicular phase?
- 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
What is the ‘two-cell hypothesis’ of oestrogen production?
- 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.
How is ovulation stimulated?
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.
What is ovulation?
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
What happens in the luteal phase?
- 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
What is luteolysis?
- 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
What happens in pregnancy?
- 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
