Female Reproductive Processes

Preantral | Primordial Follicle 

primary oocyte + simple squamous follicular cells

present before birth

Preantral | Primary Follicle

primary oocyte + simple cuboidal granulosa cells

zona pellucida forms between the primary oocyte and granulosa cells

Preantral | Secondary Follicle

primary oocyte + stratified cuboidal granulosa cells

granulosa cells now hormone sensitive and therefore can be recruited by FSH

Preantral | Late Secondary Follicle 

primary oocyte

fluid appears between granulosa cells

thecal cells form at periphery

Antral | Vesicular (Teritary) Follicle

central fluid-filled cavity (antrum) forms

innermost granulosa cells attach to zona pellucida to form the corona radiata

Antral | Mature Vesicular (Graafian) Follicle

oocyte isolated with surrounding corona radiata

primary oocyte completes meiosis I → secondary oocyte and 1st polar body

2.5cm in size

Luteal Phase | Corpus Luteum 

post ovulatory luteinised follicle

Luteal Phase | Corpuse Albicans

scar tissue remnant of corpus luteum

why does follicular atresia begin halfway through gestation?

primordial follicles present before birth spontaneously activate and develop to the secondary follicles stage but undergo atresia as further growth is dependent on gonadotrophins, which are absent until puberty

at puberty, pulsatile hypothalamic GnRH elevates LH + FSH levels, allowing further follicular growth as part of the menstrual cycle

The Stages of The Ovarian Cycle | follicular phase

1. FSH recruits a small cohort of secondary follicles for further growth

2. when thecal cells form in late secondary follicles, growth is accelerated by FSH + LH

3. LH acts on theca cells to produce androgens, FSH acts on granulosa cells to convert the androgens to estrogens

4. increasing estrogen and inhibin decrease FSH by negative feedback as follicles grow

5. follicle selection and atresia results in the maturation of 1 dominant follicle

6. ovulation

Fun Fact → Large Follicle has the most FSH receptors  and this is known as the Dominant Follicle

To help follicles mature for ovulation 

Steps of Ovulation

1. elevated estrogen from the dominant follicle initiates an LH surge by positive feedback

2. the LH surge stimulates the resumption of meiosis I in the primary oocyte, forming a secondary oocyte arrested in metaphase II, and final follicle growth and weakening of the follicle wall

3. the follicle ruptures to release the secondary oocyte and corona radiata

4. estrogen levels decline

Occurs at day 14 of menstral cycle | but the whole process takes place between day 10 and day 14.

what do prostaglandins promote during ovulation?

increased pressure via inducing muscle contraction and increased ovarian blood flow

what enzyme breaks the follicular wall?

collagenase

The Stages of The Ovarian Cycle | The Luteal Phase

It is the post-ovulatory formation then regression of the corpus luteum

1. after ovulation, LH stimulates granulosa and theca cells of the ruptured follicle to differentiate into large and small luteal cells respectively, forming the corpus luteum

2. luteinised granulosa cells secrete more progesterone than estrogen; progesterone decreases FSH and LH via negative feedback to pause folliculogenesis

3. luteinised granulosa cells also inhibit FSH by inhibin

4. estrogen declines, and progesterone becomes the dominant hormone

5. rising progesterone signal that ovulation has occurred and makes the endometrium receptive to the implantation of a fertilised gamete

how many days of the menstrual cycle for the Luteal Phase

Day 15- Day 28

Luteal Phase | Pregnant Cycle

sustained by hCG (LH-like), secreted from syncytiotrophoblasts starting 6-8 days after fertilisation and lasting for 8-12 weeks until placentation completes

continues producing progesterone to pause folliculogenesis

Luteal Phase | Non-Pregnant Cycle

Corpus Luteum  degenerates 10 days after ovulation (self-limiting)

decreased progesterone ∴ folliculogenesis resumes in next menstrual cycle

eventually forms a residual scar on the ovary called corpus albicans

why don't all the follicles die when FSH dips?

primordial and primary follicles grow independent of FSH (hormone insensitive)

what causes the peak of LH on about day 14 of the cycle?

switch from negative to positive feedback by sustained and elevated estrogen (surge centre)

what is the function of elevated FSH around day 5 of the cycle?

recruitment/ stimulation of secondary follicle growth right after menstruation

what causes the FSH peak on day 14? functions? why is it lower than LH?

1. Caused by : surge of GnRH caused by sustained elevated estrogen

2. Function: burst of follicle growth

3. It is lower than LH because: elevated inhibin partially suppresses FSH

what are the 3 layers of the uterus?

1. endometrium (inner lining)

2. myometrium (muscular layer)

3. perimetrium (outer serous layer)

what are the functions of each stratum of the endometrium?

• stratum functionalis supports implantation/ shedding during menstruation

• stratum basalis rebuilds the functional layer

what is the purpose of the uterine cycle?

prepare the uterus to receive the fertilised egg after ovulation (receptive to implantation and able to support developing embryo during pregnancy)

Uterine Cycle | Menstural Phase

Day 1 - Day 5 

shedding of the old functional endometrium layer

• CL regresses into the corpus albicans, estrogen and progesterone decrease

• when progesterone reaches its lowest level, the spiral arteries constrict and spasm (starving the endometrium of oxygen, nutrients, and hormones)

• the degenerating functional layer fragments and sloughs-off as menstrual flow

Uterine Cycle | Proliferative Phase

Day 6 - Day 14

• rebuilding of the functional layer

• high estrogen levels stimulate thickening of the endometrium, growth of endometrial glands, and the emergence of spiral arteries and progesterone receptors

• arcuate arteries in the myometrium develop branches in the endometrium

• cervical mucus thins (more hospitable to sperm)

Uterine Cycle | Secretory Phase

Day 15 to Day 28

• enrichment of blood supply and nutrient secretion by endometrial glands

• cervical mucus thickens to form the cervical plug

• progesterone binds to receptors and and stimulates the endometrial glands to produce more secretions (prepare the uterus for potential pregnancy)

Spiral Arteries 

support the functional layer

hormone-sensitive (constrict when estrogen and progesterone levels are low)

starves layer of O2 nutrients, and hormones → menses

Straight Arteries

support the basal layer

hormone insensitive

maintains reserve tissue

Ectopic Pregnancy | Most Common Site

Uterine Tubes

Ectopic Pregnancy | How is abdominal ectopic pregnancy possible

discontinuity between ovary and uterine tubes

Hormones | GnRH

hypothalamus → anterior pituitary

stimulates secretion of LH + FSH

Hormones | LH

• stimulates secretion of androgens by theca cells

• luteinisation of thecal and granulosa cells (formation of CL)

• stimulates secretion of progesterone and inhibin by lutein cells

Hormones | FSH

granulosa cells

• stimulates conversion of androgens to estrogens

• stimulates secretion of inhibin

Hormones | Inhibin

inhibits FSH

Hormones | Progesterone

• negatively regulates GnRH, LH + FSH release (pauses the menstrual cycle)

• supports the endometrium in the secretory phase

• stimulates primary and secondary female sex characteristics

how does the processes occurring in the ovarian cycle explain hormone fluctuations | Follicular Phase → answer with diagram on Luka Notes

• day 5 FSH increase recruits/ accelerates growth of secondary follicles

• granulosa cells produce estrogen

• estrogen and inhibin negatively feedback on FSH, FSH dip drives follicle selection

• estrogen levels rise with the growth of the dominant follicle

• right before ovulation, elevated estrogen levels stimulate a massive surge of LH and FSH by positive feedback (increasing pituitary sensitivity to GnRH)

how does the processes occurring in the ovarian cycle explain hormone fluctuations | Luteal Phase → answer with diagram on Luka Notes

• luteinised granulosa cells secrete progesterone (becomes predominant over estrogen)

• progesterone decreases LH and FSH by negative feedback

• in turn, the CL, unsupported by LH and FSH regresses, and progesterone levels decrease

Steps to oogensis

1. oogonium → primary oocytes (before birth) by mitosis

2. primary oocyte arrested in prophase I

3. completes meiosis I in response to LH surge → secondary oocyte and 1st polar body

4. secondary oocyte is arrested in metaphase II

5. ovulation of the secondary oocyte

6. completes meiosis II in response to fertilisation → ovum and 2nd polar body

Cohesion weaken with age, why is this a problem? 

• chromosome segregation (nondisjunction) predominantly during metaphase I

• increase in aneuploidy with increasing maternal age

How long can oocytes be kept in meiotic arrest?

50 years

meiosis I begins at [time of life] but cells are arrested in [phase]?

1. at birth

2. prophase I

at what time of life do oocytes continue meiosis? why then?

1. puberty

2. LH surge (in ovulation)

oocytes are arrested again, in what stage? and for how long?

1. metaphase II

2. until fertilisation

Theca Cells

Have LH Receptors 

Produce Androgens

Granulosa Cells

Convert Androgen into Estrogen

Receptors for FSh