Oogenesis

Question 1

What is Oogenesis?

Answer 1

the production of oocytes (mature female gametes) from primordial germ cells

Question 2

Female reproductive system

Answer 2

Uterus: supports pregnancy

Ovaries: produce oocytes and secrete hormones

Ovarian stroma: connective tissue, smooth muscle, stromal cells, developing follicles, interstitial glands

Uterine (fallopian) tube: connects ovary and uterus; important for transport of oocyte/embryo

Question 3

Purpose of the female genital tract?

Answer 3

The female genital tract serves two main reproductive functions:
Gamete production and transportation
Site of implantation; support foetal development

Question 4

The episodic nature of the menstrual cycle facilitates these two functions:

Answer 4

The episodic nature of the menstrual cycle facilitates these two functions:
During the first (oestrogenic) half, a mature oocyte is produced and made ready for fertilisation;
In the second (progestagenic) half the uterus is made ready to allow implantation and to support pregnancy

Question 5

What happens at puberty?

Answer 5

At puberty, the ovary becomes an active endocrine gland and starts to produce mature oocytes; though oogenesis begins in utero

Question 6

How does adult ovarian function differ from testicular function

Answer 6

Adult ovarian function differs from testicular function:
Far fewer oocytes are produced (around 400 in a lifetime vs millions each day)
Ovulation occurs episodically rather than continuously being produced
Ovulation stops at menopause; sperm production declines with age but continues into old age

Question 7

Describe menstrul cycle…

Answer 7

…

Question 8

Outline Oogenesis

Answer 8

Mitotic divisions all occur during foetal development

Girls are born with primary oocytes arrested at prophase I

Resumption of meiosis and development of the oocyte occurs after puberty

Asymmetric divisions produce only one mature oocyte and two polar bodies that contain chromosomes but very little cytoplasmic material

Question 9

Follicle development

Answer 9

Primordial follicle
Up to 50 years

Preantral (primary) follicle
77-85 days

Antral (secondary) follicle
8-12 days

Preovulatory (tertiary) follicle
30-36 hours

Question 10

What does the follicle provide?

Answer 10

The follicle provides the appropriate supportive environment for a developing oocyte in the same way that the seminiferous tubules support sperm development

Question 11

Describe Primordial to preantral follicle

Answer 11

Growth of follicle (20 µm diameter to around 200-400 µm)

Primary oocyte finishes growth to 60-120 µm; still arrested in prophase I of meiosis

Large amounts of mRNA and rRNA produced to build organelles and generate protein stores

Oocyte secretes glycoproteins which condense to form the zona pellucida

Granulosa cells proliferate to form thick layer around oocyte; contact between granulosa cells and oocyte is maintained through cytoplasmic processes

Ovarian stromal cells condense to form thecal layer; separated from granulosa layer by membrana propria

Question 12

Antral follicle development

Answer 12

Thecal layer expands and further develops to form two layers, theca interna and theca externa

Granulosa cells secrete fluid

Antrum: fluid-filled cavity. This stage is characterised by increasing follicle size (due to antrum)

Oocyte surrounded by granulosa layer ‘cumulus oophorus’ is suspended in follicular fluid by a thin stalk which connects to ‘mural’ granulosa cells

Oocyte continues to synthesize RNA and make proteins

Question 13

Follicle development

Answer 13

a) primordial follicle surrounded by thin layer of granulosa cells

Preantral follicle: larger oocyte with zona pellucida; expanding granulosa cell layer

b) Antral follicle: Oocyte with zona pellucida, surrounded by cumulus cells; vast number of granulosa cells; antrum filled with follicular fluid

Question 14

Communication between oocyte and granulosa cells

Answer 14

Granulosa cells are connected to oocyte through cytoplasmic processes

Gap junctions form between adjacent granulosa cells and at the oocyte surface

Extensive network of communication which allows transfer of amino acids and nucleotides to growing oocyte

Granulosa-oocyte complex resembles Sertoli cell- spermatogenic complex

Question 15

Regulation of follicle development

Answer 15

Very early primordial follicle development is stimulated locally via growth factors and cytokines; a few follicles recommence growth every day

Further follicle development is dependent on the pituitary; absence of pituitary input results in atresia

FSH-knockout mice arrest follicular development at the preantral stage; LH-knockout mice stop at the antral phase

Only cells in theca interna bind LH; only granulosa cells bind FSH

Question 16

Regulation of the HPG axis in females

Answer 16

Hormone levels vary enormously at different stages of the menstrual cycle (menstrual cycle lasts ~28 days; ovulation ~day 14)

Question 17

LH and FSH regulation in HPG axis in females

Answer 17

LH and FSH output is predominantly regulated by secretory products from the ovary

Negative feedback: oestrogens, progestogens and inhibins exert a depressant effect on gonadotrophin output

Positive feedback: Activin A enhances FSH expression; high levels of Oestradiol (an oestrogen) causes a surge of LH (and a smaller peak in FSH)

Question 18

How do Oestradiol act in different points of menstral cycle?

Answer 18

Oestradiol acts in different ways at different points in the menstrual cycle: at low concentrations it acts to negatively regulate LH expression but at high levels it acts to positively regulate expression

Question 19

What happens in response to FSH and LH stimulation?

Answer 19

In response to FSH and LH stimulation, the follicles grow and the eggs mature

Question 20

What do Thecal cells produce?

Answer 20

Thecal cells produce the androgens androstenedione and testosterone as a result of LH stimulation

Question 21

What do the antral follicles produce?

Answer 21

The antral follicles produce and release increasing amounts of steroid hormones as they grow

Question 22

Role of Granulosa cells

Answer 22

Granulosa cells convert androgens (from thecal cells) to oestrogens oestradiol 17β and oestrone upon FSH stimulation

Question 23

Steroid conversion in antral follicle

Answer 23

Thecal cells synthesize androgens (androstendione and testosterone) from acetate and cholesterol; they also generate low levels of oestrogens

Some of these androgens are converted to oestrogens (oestradiol 17β and oestrone) in the granulosa cells

Androgens also stimulate aromatase activity and therefore promote oestrogen synthesis

Later in the menstrual cycle, granulosa cells express LH receptors; LH stimulation results in synthesis of progesterone

Question 24

HPG axis in females

Answer 24

Increase in androgens causes granulosa cell proliferation and increase in oestrogen production

Oestrogens themselves also promote granulosa proliferation

Causes an oestrogen surge which then exerts positive feedback to stimulate LH surge

Question 25

Ovulation - Antral follicles

Answer 25

Antral follicles will die unless an LH surge occurs; LH surge coincides with expression of LH receptors on outer granulosa cells

Question 26

Ovulation - Effects of LH surge

Answer 26

Effects of LH surge:
Entry into preovulatory phase of growth
Nuclear membrane breaks down and meiosis resumes up to metaphase II. Half of the chromosomes but majority of cytoplasm go to one cell (the secondary oocyte); rest is the first polar body (dies)
Cytoplasmic maturation occurs (synthesis of specific set of proteins, reorganisation of microtubules)
Within two hours of start of LH surge there is a transient rise (then decline) in output of follicular oestrogens and androgens
Follicle ruptures and oocyte is carried out in follicular fluid

Question 27

Ovulation - Granulosa cells

Answer 27

Granulosa cells then switch from oestrogen production to progesterone production under LH stimulation. Forms positive feedback loop where granulosa cells are then stimulated by their own progesterone resulting in exponential increase in progesterone release

Question 28

What does progesterone increase result in?

Answer 28

This progesterone increase:
depresses growth of less mature follicles

promotes transition to progestagenic phase of ovarian cycle

Question 29

The corpus luteum

Answer 29

Following ovulation, the empty follicle collapses and becomes highly vascularised – the corpus luteum

Made up of large lutein cells (granulosa cells) which synthesize progestagens, and small lutein cells (thecal cells) which produce progesterone and androgens

Corpus luteum also secretes Inhibin A and oxytocin; these hormones are important in maintaining the corpus luteum and for luteolysis

LH is required for luteinisation; prolactin, oestrogen and progesterone are required to maintain corpus luteum

Corpus luteum undergoes luteolysis (life ranges from 12-14 days in humans)

Question 30

Regulation of the HPG axis in females - Progesterone

Answer 30

Progesterone also has two main effects:
High concentration seen in luteal phase of menstrual cycle (after ovulation) enhances the negative feedback of Oestradiol
Additionally, the positive feedback effect of Oestradiol is blocked
Progesterone acts on both the hypothalamus and the pituitary
The result is a fall in FSH and LH levels after ovulation

Question 31

Regulation of the HPG axis in females - Activin

Answer 31

Activin positively regulates FSH secretion at the level of the pituitary

Question 32

Regulation of the HPG axis in females - Inhibin B

Answer 32

Inhibin B selectively negatively regulates FSH secretion at the level of the pituitary; Inhibins also act as Activin antagonists

Question 33

Self assessment questions

Answer 33

What is the significance of mitosis in germ cell development? How and why does it differ between men and women?

How does the follicle support oocyte growth and development?

What are the key positive and negative feedback loops in the HPG axis?