Oogenesis Flashcards
What is oogenesis?
The production of oocytes (mature female gametes) from primordial germ cells
What are the main components of the female reproductive system? (4)
- Uterus
- Ovaries
- Ovarian stroma
- Uterine (fallopian) tube
What is the function of the uterus?
Supports pregnancy
What is the function of the ovaries? (2)
- Produce oocytes
- Secrete hormones
What is the ovarian stroma? (4)
- Connective tissue
- Smooth muscle
- Stromal cells
- Developing follicles
What is the function of the uterine (fallopian) tubes? (2)
- Connects ovary and uterus
- Important for transport of oocyte/embryo
What are the 2 main reproductive functions of the female genital tract?
- Gamete production and transportation
- Site of implantation so support of foetal development
What 2 functions are facilitated by the episodic nature of the menstrual cycle?
- First (oestrogenic) half: a mature oocyte is produced and made ready for fertilisation
- Second (progestogenic) half: the uterus is made ready to allow implantation and to support pregnancy
What are the phases of the menstrual cycle? (2)
- First half: oestrogenic/follicular
- Second half: progestogenic/luteal
How does adult ovarian function differ from testicular function? (3)
- Far fewer oocytes are produced (around 400 in a lifetime vs millions each day)
- Ovulation occurs episodically rather than continuous production
- Ovulation stops at menopause whereas sperm production declines with age but continues into old age
What are the main features of oogenesis? (6)
- Primordial germ cells in the embryo differentiate into oogonia (equivalent to spermatogonial stem cells)
- Oogonia self renew by mitosis to expand the stem cell pool
- All mitotic replication occurs during foetal development and then cells enter meiosis so females are born with primary oocytes arrested at prophase I whereas mitosis occur in puberty in males
- Resumption of meiosis and development of the oocyte occurs after puberty
- Asymmetric divisions (vs symmetrical in males) produce only one mature oocyte and two polar bodies that contain chromosomes but very little cytoplasmic material
- Mature oocyte is arrested at metaphase II after ovulation and meiosis II is only complete after fertilisation
What are the stages of follicle development?
- Primordial follicles form during foetal development and develop into preantral (primary) follicles during puberty
- Preantral follicle becomes the antral (secondary) follicle then the preovulatory (tertiary) follicle
- Preovulatory follicle burst when the egg is released at ovulation and the empty follicle becomes the corpus luteum
What is a follicle? (2)
- Fluid filled sacs in the ovaries which contain developing oocytes
- Provides the appropriate supportive environment for a developing oocyte in the same way the seminiferous tubules support sperm development
How does the primordial follicle become the preantral follicle? (7)
- Follicle grows (20um diameter to 200-400um)
- Primary oocyte finishes growth to 60-120um while still arrested in prophase I
- Large amounts of mRNA and rRNA are produced to build organelles and generate protein stores
- Oocyte secretes glycoproteins which condense to form the zona pellucida (extracellular matrix)
- Granulosa cells surrounding the oocyte proliferate to form a thick layer
- Contact between granulosa cells and oocyte is maintained through cytoplasmic processes
- Ovarian stromal cells condense to form thecal layer which is separated from the granulosa layer by membrana propria
How does the preantral follicle become the antral follicle? (5)
- Thecal layer expands and further develops to form 2 layers, theca interna and theca externa
- Granulosa cells expand and secrete fluid which builds up in pockets within the granulosa cell layer
- Antrum is a fluid filled cavity so this stage is characterised by increasing follicle size due to antrum
- The oocyte surrounded by granulosa layer cumulus oophorus is suspended in follicular fluid by a thin stalk which connects to the mural granulosa cells
- Oocyte continues to synthesis RNA and make proteins
What are the somatic cells which supporting oogenesis? (2)
- Granulosa cells
- Thecal cells
How do granulosa cells communicate with the oocyte? (4)
- Oocyte isn’t connected to the blood supply so rely on granulosa cells for support
- Granulosa cells are connected to the oocyte through cytoplasmic processes
- Gap junctions form between adjacent granulosa cells and at the oocyte surface which resembles the Sertoli cell-spermatogenic complex
- Extensive network of communication which allows transfer of amino acids and nucleotides to the growing oocyte
How is follicle development regulated? (2)
- Very early primordial follicle development is stimulated locally via growth factors and cytokines
- Further follicle development is dependent on pituitary signals (FSH and LH) and absence of this results in atresia (degeneration)
What happens to follicular development when FSH and LH are knocked out? (3)
- FSH knockout mice arrest follicular development at the preantral stage
- LH knockout mice at the antral stage
- Therefore FSH is required earlier on in follicular development than LH
Which cells respond to FSH and LH in the follicular phase? (2)
- Only cells in the theca interna bind LH
- Only granulosa cells bind FSH
What do thecal cells produce in response to LH in the follicular phase? (2)
- Androgens (androstenedione and testosterone)
- Progestagens
What do granulosa cells produce in response to FSH in the follicular phase? (4)
- Inhibins
- Activins
- Progestagens
- Convert some of the androgens from thecal cells to oestrogens (oestradiol 17-beta and oestrone) upon FSH stimulation
How do follicles respond to FSH and LH stimulation? (3)
- Follicles grow
- Eggs mature
- Sex steroids produced as a result of pituitary stimulation causes proliferation of somatic cells so positive feedback makes the follicle grow even more
How does steroid conversion occur in the antral follicle? (4)
- Thecal cells make androgens (androstendione and testosterone) and low levels of oestrogens
- Some of these androgens are converted to oestrogens (oestradiol 17-beta and oestrone) in the granulosa cells via aromatase enzyme
- Androgens also stimulate aromatase activity
- Follicular phase: LH stimulates thecal cells only to produce androgens, luteal phase: granulosa cells express LH receptors and LH stimulation causes progesterone synthesis
How does oestrogen feedback cause ovulation? (4)
- Follicular phase: LH causes thecal cells to produce androgens which causes granulosa cell proliferation and increased oestrogen production
- Oestrogens further promote granulosa proliferation (positive feedback)
- Low oestrogen levels cause inhibition of the hypothalamus and pituitary and therefore low LH production
- High oestrogen levels exert positive feedback on the hypothalamus and pituitary, causing an LH surge which triggers ovulation
Why do LH levels immediately drop after the surge at ovulation? (2)
- Rising levels of progesterone which exerts negative feedback onto the hypothalamus and pituitary (FSH and LH)
- Cancels out oestrogens positive feedback control
What are hormone levels like in the luteal phase of the menstrual cycle? (2)
- FSH and LH levels are low to prevent maturation of further follicles during preparation for potential pregnancy
- Progesterone levels are high to create nutrient/blood rich environment in uterus ready for implantation
What occurs at ovulation? (2)
- Antral follicles will die unless an LH surge occurs
- LH surge coincides with expression of LH receptors on outer granulosa cells which causes them to start making progesterone (causing rising progesterone levels after ovulation)
What are the effects of the LH surge on the follicle/oocyte? (4)
- Entry into preovulatory phase of follicle development
- Nuclear membrane breaks down and meiosis resumes up to metaphase II, half of the chromosomes but majority of the cytoplasm goes to one cell (secondary oocyte) and the rest is the first polar body which dies
- Cytoplasmic maturation occurs (synthesis of specific set of proteins, reorganisation of microtubules)
- Follicle ruptures and oocyte is carried out in follicular fluid into the top of the fallopian tube
How does the behaviour of the granulosa cells change after ovulation? (2)
- Granulosa cells switch from oestrogen production to progesterone production under LH stimulation which forms a positive feedback loop where granulosa cells are stimulated by their own progesterone causing more progesterone release
- Progesterone increase prevents growth of further follicles and promotes transition into the progestagenic phase (mimicked by hormonal contraceptives)
What is the corpus luteum? (7)
- The empty follicle which collapses and becomes highly vascularised after ovulation and is an important transient endocrine gland
- Large lutein cells (granulosa cells) make progestagens
- Small lutein cells (thecal cells) make progesterone and androgens
- Also secretes inhibin and oxytocin which are important for both maintaining the corpus luteum and for luteolysis
- LH is required for luteinisation
- Prolactin, oestrogen and progesterone are required to maintain the corpus luteum
- Undergoes luteolysis (breakdown) after 12-14 days, uterine lining breaks down, menstruation
What is luteinisation?
Conversion of granulosa and thecal cells to luteal cells to form the corpus luteum
How is the HPG axis regulated in females? (4)
- Oestradiol negatively regulates LH at low concentrations but positively regulates LH at high concentrations
- High concentration of progesterone blocks oestradiol positive feedback and enhances the negative feedback of oestradiol in the luteal phase, as well as also inhibiting the hypothalamus and pituitary causing a fall in FSH and LH after ovulation
- Activin positively regulates FSH secretion at the level of the pituitary
- Inhibin B selectively negatively regulates FSH secretion at the level of the pituitary and acts as activin antagonists
What are the similarities between spermatogenesis and oogenesis? (5)
- Both sets of cells undergoing meiosis are protected from the immune system as neither have a direct bloody supply
- Both require supporting somatic cells
- Similar feedback of sex steroids in HPG axis
- Both feature conversion of sex steroids by supporting somatic cells
- Both produce haploid gametes
What are the differences between spermatogenesis and oogenesis? (5)
- Meiotic divisions are asymmetrical in females but symmetrical in males
- Female gamete production is episodic but male is continuous
- Mitotic divisions of oogonia only occur during foetal development but mitotic divisions of spermatogonia continue into puberty
- Fewer total number of mature oocytes produced compared to sperm
- Oogenesis stops at menopause but spermatogenesis continues into old age