W4 - FEMALE REPRODUCTIVE SYSTEM Flashcards
1
Q
Explain the ovarian cycle
A
- Follicles
- These are embedded in highly vascular connective tissue in the ovary and contain many saclike structures called ovarian follicles
- Each contains an immature egg (oocyte), encased by one or more layers of different cells
- These surrounding cells are called follicle cells
- When there is only one layer of surrounding cells - follicle cells
- When there is more than one layer of surrounding cells - granulosa cells
- These are embedded in highly vascular connective tissue in the ovary and contain many saclike structures called ovarian follicles
- Follicles are distinguished by their structure
- Primordial follicles
- Single layer of follicle cells
- More mature
- Several layers of granulosa cells
- Fully mature vesicular follicle
- Central fluid-filled cavity
- Primordial follicles
- When mature, the follicle extends from the ovarian cortex and builds from the surface of the ovary
- The oocyte sits on a stalk of granulosa cells
2
Q
Explain oogenesis
A
- Oogenesis can take many years, starting at the time of birth and will not be complete until 20-40 years later
- The stem cells replicate just before birth before they commit to becoming oocytes
- They then commit and differentiate into primary oocytes and continue to develop
- At the time of puberty, a small portion of the population is activated to resume meiosis
- They respond to an LH surge
- The process of meiosis is asymmetrical - does not result in all the same products
- Creates polar bodies that degenerate
- Most of the cytoplasm is held in the secondary oocyte
- Extrusion of DNA is in the polar body
- This allows for one large, functional body
- Creates polar bodies that degenerate
3
Q
Explain oocyte transformation pre-puberty, after puberty and during sperm penetration
A
- Pre-puberty
- In the foetal period, the oogonia (diploid stem cells of the ovaries) multiply rapidly by mitosis
- As the oogonia gradually transform into primary oocytes, the primary primordial follicles appear
- A single layer of flattened follicle cells
- Primary oocytes being the first meiotic division, but become “stalled” in late prophase I and do not complete it until puberty
- By birth, a female has her lifetime supply of primary oocytes (no more replication of stem cells can occur) and all stem cells commit to the oogenic pathway (none remain to replenish the supply, unlike sperm)
- Overtime, quiescent primordial follicles are recruited into a growing pool of primary follicles
- This begins in foetal life and continues throughout life until the supply of primordial follicles is depleted (menopause)
- After puberty
- Before puberty, all of the primordial follicles are recruited to undergo atresia (apoptosis)
- At the beginning of puberty, the FSH rescues a small number of growing follicles from that fate each month
- At each cycle, one of the rescued follicles is selected to become the dominant follicle, and continue meiosis I, ultimately producing two haploid cells that are dissimilar in size
- The smaller is the first polar body and the larger contains nearly all of the cytoplasm - the secondary oocyte
- Those maturing follicles not selected undergo atresia
- The first polar body may continue its development and undergo meiosis II, producing two even smaller polar bodies
- The secondary oocyte arrests in metaphase II, and it is this cell that is ovulated
- Before puberty, all of the primordial follicles are recruited to undergo atresia (apoptosis)
- Sperm penetration
- If there is no sperm penetration, the oocyte deteriorates
- If there is sperm penetration, the oocyte quickly undergoes meiosis I, yielding a large ovum and a tiny second polar body
4
Q
What are the differences in gametogenesis in males and females?
A
- Males - spermatogenesis
- Unlimited amount of sperm
- Produce 400 million sperm per day and replenished by mitosis
- Continuous
- Continuous meiosis
- Asynchronous continuous production
- Symmetrical division
- 4 functional gametes
- Unlimited amount of sperm
- Females - oogenesis
- Limited
- Puberty to menopause (<500 actually ovulated)
- Oogonia do not replenish
- All stem cells commit to becoming oocytes
- Discontinuous
- Interrupted meiosis (complete when fertilised)
- Monthly production (female reproductive cycle)
- Asymmetric division
- 1 functional gamete
- 3 non-functional gametes
- Limited
- Error rate
- As many as 20% of oocytes have problems, compared to 3-4% of sperm
- With meiotic disruption, more spermatocytes in males cease meiosis, whereas females continue
5
Q
What are the problems with meiotic arrest?
A
- Prolonged arrest in prophase 1 can last up to 50 years
- Cohesive problems that keep sister chromatids together weaken with age, causing
- Incorrect microtubule-centromere attachment
- Chromosome segregation errors (non-disjunction) predominantly during meiosis 1
- Causes increase in aneuploidy with increasing maternal age
6
Q
What are the phases of the ovarian cycle? Explain
A
- There are two main phases in the ovarian cycle
- Follicular phase
- Period when the dominant follicle is selected and begins to secrete large amounts of oestrogen
- Generally, lasts from days 1-14, at which point ovulation generally occurs
- Period when the dominant follicle is selected and begins to secrete large amounts of oestrogen
- Luteal phase
- Period of corpus luteum activity
- Generally, occurs between days 15-28
- Period of corpus luteum activity
- Follicular phase
- Only 10-15% of women have naturally occurring 28-day cycles, with it being common to have cycles between 21-40 days
- Follicular phase and time of ovulation vary, however the luteal phase is always 14 days from the time of ovulation to the end of the cycle
7
Q
What is the follicular phase? Explain
A
- The maturation of the primordial follicle involves preantral and antral phases, as well as several other events
- Preantral phase - GnRH-independent
- Intrafollicular
- Paracrine such as cytokines and growth factors control oocyte and follicle-development
- Involves the primordial, primary, secondary and late secondary follicle stage
- Intrafollicular
- Antral phase - Directed by FSH and LH
- Activated follicles grow tremendously and the primary oocyte in the dominant follicle resumes meiosis I
- Involves the vesicular/tertiary, and mature vesicular/graafian/preovulatory follicle stages
- Preantral phase - GnRH-independent
- There are always several follicles at different stages of maturation
- When LH stimulates the ovaries, the oocyte that is most advanced will ovulate
- FSH is a survival factor for antral follicles and plays a role in selecting the dominant follicle
- Uncertain how it is selected
- In 1-2% of ovulations, more than one oocyte is ovulated
- Increases with age and can result in fraternal twins
- Sometimes these oocytes will have different times of release
- Identical twins are born by the fertilisation of a single oocyte by a single sperm, followed by the separation of the fertilised egg’s daughter cells during early development
- Increases with age and can result in fraternal twins
8
Q
Explain the processes involved in the follicular phase
A
- Primordial follicle becomes a primary follicle
- When a primordial follicle is activated (almost a year before its possible ovulation), the squamous like cells surrounding the primary oocyte grow, becoming cuboidal cells and the oocyte enlarges
- The follicle is now called a primary follicle
- When a primordial follicle is activated (almost a year before its possible ovulation), the squamous like cells surrounding the primary oocyte grow, becoming cuboidal cells and the oocyte enlarges
- A primary follicle becomes a secondary follicle
- The follicular cells proliferate, forming a stratified epithelium around the oocyte
- As soon as more than one cell layer is present, the follicle is called a secondary follicle, and the cells take on the name granulosa cells
- Granulosa cells are connected to developing oocytes by gap junctions, through which ions, metabolites and signalling molecules can pass
- From this point on, bidirectional “conversations” occur between oocyte and granulosa cells, so they guide one another’s development - one signal is to tell the oocyte to grow, the other signals dictate the asymmetry in the future egg
- Oocyte grows tremendously in this stage and FSH receptors begin to appear on the granulosa cells - still in the pre-antral phase
- Secondary follicles become a late secondary follicle
- Layer of connective tissue and epithelial cells condense around the follicle, forming the thecal follicle (box around the follicle)
- As the follicle grows, the thecal and granulosa cells cooperate to produce oestrogens
- In response to LH, the inner thecal cells produce androgens, which the granulosa cells convert to oestrogens
- At the same time, the oocyte secretes a glycoprotein-rich substance that forms a thick transparent extracellular layer - zona pellucida that encapsulates it
- It is a barrier to poly-sperm fertilising one egg
- Layer of connective tissue and epithelial cells condense around the follicle, forming the thecal follicle (box around the follicle)
- A late secretory follicle becomes a vesicular (Antral/tertiary) follicle
- The late secretory follicle causes the events of the antral phase
- The follicle reaches the critical preovulatory stage and all granulose cells bear FSH receptors
- When 6-7 layers of granulosa cells present, the fluid between the granulosa cells coalesces to form a large fluid-filled cavity called the antrum (cave)
- Distinguishes the early vesicular follicle from the late secondary follicle
- Antrum continues to expand with fluid until it isolates the oocyte, along with its’ surrounding capsule of granulosa cells called a corona radiata
- When 6-7 layers of granulosa cells present, the fluid between the granulosa cells coalesces to form a large fluid-filled cavity called the antrum (cave)
- The primary oocyte completes meiosis I to form the secondary oocyte and the first polar body
- The oocyte is now ready for ovulation
- Granulosa cells prevent the oocyte from leaving
- Estimated that follicle growth from the primordial stage to this stage takes about a year
- Each follicle that ovulates must have begun to grow 10-12 cycles beforehand
- The oocyte is now ready for ovulation
- Ovulation
- The wall swells outwards and ruptures, expelling the secondary oocyte, still surrounded by the corona radiata, into the peritoneal cavity
9
Q
What is the luteal phase? Explain
A
- After ovulation, the ruptured follicle collapses and the antrum fills with clotted blood
- Known as the corpus hemorrhagicum - eventually absorbed
- Remaining granulosa cells enlarge and, with the internal thecal cells, form the corpus luteum
- Secretes progesterone and some oestrogen
- If pregnancy does not occur
- The corpus luteum begins degenerating within 10 days and the hormonal output ends
- All that remains is the scar called the corpus albicans
- The last 2-3 days of the luteal phase is when the endometrium begins to erode - called the luteolytic/ischemic phase
- If pregnancy does occur, the corpus luteum persists until the placenta is ready to take over its hormone-producing duties in about 3 months
10
Q
What are the stages of follicle development? Explain
A
- Different stages of maturation
- Primordial follicle
- Single layer of squamous-like follicle cells surrounds the oocyte
- The development of all of these cells are on the periphery - they can be seen surrounding the oocyte
- Primary follicle
- Single layer of cuboidal or columnar type follicle cells surrounding the oocyte
- Ill-defined squamous cells become cuboidal cells around the oocyte
- Secondary follicle
- Two or more layers of granulosa cells surround the oocyte
- Replication of the cuboidal cells to form stratified cuboidal cells - granulosa
- Late secondary follicle
- Small fluid filled spaces appear between the granulosa cells
- Theca and zona visible
- Accumulation of granulosa cells work in harmony to produce oestrogen
- Secrete fluid
- Zona pellucida forms
- Follicle becomes sensitive to hormone stimulation to grow
- Vesicular/tertiary follicles
- A central fluid filled cavity (antrum) and corona radiata form
- Pre-ovulating follicle
- A follicle that is about to ovulate
- Large and selected to be ovulated - grow to 2.5cm before ovulation (graafian/pre-ovulatory follicle)
- Undergoes meiosis 1
- Corpus Luteum
- Post ovary luteinised follicle
- Produces progesterone that negatively inhibits LH
- Corpus albicans
- Left over scar tissue that remains in the ovary after ovulation
- Menopause
- Strong indicator of the end of the reproductive lifespan of the ovaries
- Lots of corpora albicantia present on the ovaries and no developing follicles
- Primordial follicle
11
Q
Which hormones are involved in the ovarian cycle? State their site of relase, target and role in the human body
A
- GnRH
- Site of release
- Hypothalamus
- Target
- Anterior pituitary
- Role
- Stimulates LH and FSH secretions
- Site of release
- LH
- Site of release
- Anterior pituitary
- Target
- Thecal cells
- Role
- Stimulates the release of androgens from thecal cells
- Target
- Follicles
- Role
- Maturation and development
- Target
- Primary oocytes
- Role
- At surge, rouses primary oocyte dominant follicles from rest and completes the first division – secondary oocyte
- Target
- Day 14
- Role
- Triggers ovulation – increases local vascular permeability and triggers an inflammatory response that promotes release of metalloproteinase enzyme that weaken the ovary wall; the blood stops following through the protruding part of the follicle wall, causing it to thin, bulge and then rupture
- Target
- Corpus luteum
- Role
- Triggers the formation
- Site of release
- FSH
- Site of release
- Anterior pituitary
- Target
- Granulosa cells of the late secondary and vesicular follicles
- Role
- Conversion of androgens to oestrogens in granulosa cells; inhibin secretion; at the start of each month, some follicles from apoptotic deaths; selects primary follicles
- Target
- Oocyte
- Role
- Causes egg to mature
- Target
- Follicles
- Role
- Development of ovarian follicles and growth/maturation
- Site of release
- Oestrogen
- Site of release
- Granulosa cells (derived from androgens from thecal cells)
- Target
- Anterior pituitary and hypothalamus
- Role
- Negative/positive regulation of GnRH, LH and FSH
- Target
- Endometrium
- Role
- Stimulates the thickening of the endometrium
- Target
- Whole body
- Role
- Primary and secondary sex characteristics; thickening of cervical mucus for each passage of sperm
- Target
- Cervical mucus
- Role
- Clear, watery, non-viscous mucus; glycoproteins assemble to form elongated fibres that allow sperm to penetrate the mucus and pass upwards through the cervix into the uterus; this coincides with ovulation
- Site of release
- Inhibin
- Site of release
- Granulosa cells, corpus luteum
- Target
- Anterior pituitary
- Role
- Inhibits FSH
- Site of release
- Progesterone
- Site of release
- Corpus luteum
- Target
- Hypothalamus and anterior pituitary
- Role
- Negatively regulates GnRH, LH and FSH release
- Target
- Endometrium
- Role
- Stimulates endometrium preparation (secretory phase) for implantation
- Target
- Whole body
- Role
- Primary and secondary sex characteristics; thickens cervical mucus (for sperm blockage)
- Site of release
- Leptin
- Site of release
- Adipose tissue
- Target
- Hypothalamus
- Role
- Onset of puberty – whether energy stores are sufficient to support the high energy demands of reproduction or not
- Site of release
12
Q
Explain the processes involved in the endocrine control of ovarian cycle
A
- GnRH stimulates FSH and LH secretion
- FSH and LH stimulate follicles to grow, mature and secrete hormones
- FSH - acts on granulosa cells of the late secretory and vesicular follicles, causing them to release oestrogen (cannot act on granulosa cells until secondary follicles begin to display FSH receptors)
- LH -causes thecal cells to release androgens - diffuse through the basement membrane where the granulosa cells convert them into oestrogens
- Only small amounts enter the blood as they are almost all converted into oestrogens within the ovaries
- Negative feedback inhibits GnRH release
- As oestrogen levels in the plasma rise due to stimulation by LH and FSH, they exert negative feedback on the hypothalamus and anterior pituitary, inhibiting FSH and LH
- In the ovary, oestrogen enhances the output of oestrogens by intensifying the effect of FSH on follicle maturation
13
Q
What are the phases of the ovarian cycle? Explain
A
- The cycle can be divided into two main phases
- Follicular phase (Days 1-14) - maturation of follicles leading to ovulation
- Luteal phase (Days 15-28) - post-ovulatory formation then regression of the corpus luteum
- Typical ovarian cycle length = 28 days
- Follicular phase - days 1-14
- Pre-puberty
- Primordial follicles spontaneously activate
- After puberty
- Growth of a small cohort of secondary follicles is accelerated during the follicular phase by FSH and LH
- This is the growing phase
- There is an increase in oestrogen and inhibin, with decreased FSH
- Follicle selection and atresia results in the maturation of only one dominant follicle per cycle
- At ovulation, this dominant pre-ovulatory (graafian) follicle reaches a diameter of 2.5cm
- Pre-puberty
- Ovulation
- In a normal 28-day cycle, ovulation occurs at 14 days after the onset of menstruation
- Sustained, elevated oestrogen from the dominant follicle triggers an LH surge
- Resumption of meiosis in oocyte to metaphase II
- Final follicle growth, weakening of follicle wall and ovulation
- Follicle wall rapidly swells, ruptures, and releases oocyte surrounded by a ring of granulosa cells (Cumulus cells or corona radiata)
- Shortly after ovulation, oestrogen levels decline due to the ovary being damaged
- Luteal Phase - days 15-28
- After ovulation, LH stimulates granulosa and thecal cells of the ruptured follicle to rapidly differentiate into lutein cells
- Luteinisation forms a new endocrine structure - the corpus luteum
- Corpus luteum - secretes large amounts of oestrogen and progesterone - shuts down further folliculogenesis (FSH and LH)
- In non-pregnant cycle, corpus luteum degenerates approximately 10 days after ovulation
- Corpus luteum regression = Decreased oestrogen/progesterone = Increased folliculogenesis
- Eventually forms a residual scar on the ovary called the corpus albicans
14
Q
What are the three layers of the uterus? Explain the function of the uterus and calculate the number of eggs (on average) a woman starts with
A
- Three layers of the uterus
- Perimetrium - peritoneum in origin
- Myometrium - bulky contractile smooth muscle
- Endometrium - two layers
- Stratum functionalis - shed during menstruation
- Stratum basalis - rebuilds the functional layer (stem cells)
- Function
- Primary function of the cycle is to prepare the uterus to receive the fertilised embryo after ovulation occurs
- Cycle length
- Average length of a lunar month - 29.5 days
- Can vary greatly - 25-35 days
- The younger a woman is, the longer the cycle
- 15-19 years - 35 days (More variable in teenage years)
- 30 years - 30 days
- 35 years - 28 days
- With a cycle length of 28 days, a woman would ovulate 13 ova per year = 481 ova over 37 years from puberty to menopause
- Therefore, on average, a woman starts with roughly 500 eggs
15
Q
What are the three phases of the uterine (menstrual) cycle? Explain
A
- Three main phases
- Menstrual phase - Days 1-5
- Destructive phase (menses)
- Shedding of the functional endometrium layer
- Proliferative phase - Days 6-14
- Follicular/oestrogenic phase
- Rebuilding of the functional layer
- Secretory phase - Days 15-28
- Luteal/progestational phase
- Enrichment of the blood supply and nutrient secretion by endometrial glands
- Menstrual phase - Days 1-5
