Physiology Of The Ovarian Follicle Flashcards
Occurs during embryonic development:
What happens to meiotic arrest (prophase I)?
Meiosis I finishes before ____.
What happens in meiotic arrest (metaphase II)?
Resumption of meiosis II at ____; how?
Elevated levels of cAMP, large antral follicles gain meiotic competence: stay in arrest until LH surge
Ovulation; polar body 1 extruded
Elevated levels of MAPK proteins
Fertilization; rapid degradation of MAPK; polar body 2 extruded
Adult ovary can be divided into two layers
Inner medulla: highly vascular; contains nerves, interstitial cells, lymphatics
Outer cortex: densely cellular stroma; ovarian follicles reside within stroma at different point of development
What is the function of the ovary in the follicular phase of the ovarian cycle?
Ovarian follicle: functional unit
Performs gametogenic and endocrine fx
Pre-menopausal cycling woman contain follicular structures at many different stages
What is the first stage of the ovary during the follicular cycle?
Describe the primordial follicle?
What is it arrested in?
What surrounds it?
What does it release?
What does it represent?
Primordial follicle
Primary oocyte arrested in 1st meiotic prophase
Surrounded by a single layer of pregranulosa cells
Release paracrine factors, no steroid hormones
Represents the ovarian reserve, most undergo atresia
What does the primordial follicle become?
When does the growing preantral follicle develop?
What is the primary follicle?
Why do they increase in size?
What do they produce?
Primary follicle (growing preantral follicle)
Prior to formation of fluid-filled antral cavity
Central primary oocyte; single layer of granulosa cells take on cuboidal shape
Increase in size of follicle due to growth of primary oocyte
Early production of secreted glycoproteins (ZP1, ZP2, ZP3)
What does the primary follicle become?
What is the secondary follicle?
What do they secrete?
What is the difference between the theca cells?
Secondary follicle (growing preantral follicle)
Primary oocyte surrounded by 3-6 layers of cuboidal granulosa cells
Secretion of paracrine factors to induce local stromal cells to differentiate into thecal cells
Theca interna: inner glandular; highly vascular
Theca externa: fibrous-like
What does the follicle need to become a secondary follicle?
Where do they follicles migrate?
What do the follicles release?
What also begins to develop? Fx?
Increased vascularization
From outer cortex to inner cortex, closer to ovarian vasculature
Angiogenic factors that induce the development of 1-2 arterioles; generate vascular wreath around the follicle
Zona pellucida: provides binding sites for the sperm during fertilization
What is maintained n the growing preantral follicle?
___ relationship provides for a nutritional network for growing oocyte.
____ penetrate the zona pellucida and form ____ at the oocyte surface between adjacent granulosa cells.
Contact between the granulosa and oocyte
Avascular
Cytoplasmic processes; gap junctions (basis for communication)
Nutrients, waste, and signals going back and forth between granulosa and oocyte
The growing preantral follicles have ____ endocrine function.
Granulosa cells express what? And do not produce what?
What cells express LH receptors? What is their major product?
Minimal
FSH receptors dependent on paracrine factors from oocyte for growth
Do not produce ovarian hormones at this point
Thecal cells; androstendione (minimal production)
What happens during the preantral to antral transition?
Proliferation of granulosa cells
Continued increase in follicular size
Production of follicular fluid from granulosa cell secretions and thecal vasculature begins to appear between granulosa cells
Fluid drops coalesce to form a singular follicular antrum -> marks beginning of antral phase (cells now dependent on gonadotropins; before it was dependent on paracrine signals)
The appearance of the antrum marks the beginning of the ___ phase.
Increase in the follicular size depends on what?
Oocyte becomes suspended in what?
Antral
Increase in antral size, volume of follicular fluid, proliferation of granulosa cells
Fluid surrounded by a dense mass of granulosa cells (cumulus oophorous and corona radiata)
What happens in antral phase?
What two types of granulosa cells develop? What is their fx?
Increase in granulosa cells
Mural granulosa (stratum granulosum): outer wall of follicle; becomes highly steroidogenic (produce estrogen and progesterone); become the corpus luteum
Cumulus cells (cumulus oophorus/corona radiata): maintain gap and adhesion junctions with oocyte; released during ovulation with oocyte
Growth at the antral stage becomes responsive to ___.
What do the theca interna cells respond to? What is their fx?
What do the granulosa cells respond to? What is their fx?
Gonadotropins
LH; Synthesize androgens from acetate and cholesterol; produce androstenedione
FSH; convert androstenedione from thecal cells to estradiol using aromatase; induces expression of LH receptors in late follicular phase
Oocyte grows ___ in the early stages of antral follicles; growth ____ in larger follicles
At antral stage, oocyte becomes competent to complete ____.
However, larger antral follicles stay arrested in ____ until ____.
Meiotic arrest achieved by maintenance of _____ in the mature oocyte
Rapidly; slows
Meiosis I at ovulation
Meiosis I; midcycle LH surge
Elevated cAMP levels
What follicles are recruited to being development each monthly cycle?
When is one dominant follicle selected?
How is it selected?
What happens to the other follicles?
Several large antral follicles
Early follicular phase
Largest follicle with most FSH receptors (highest sensitivity) becomes dominant follicle
Undergo atresia/ apoptosis of oocytes and granulosa cells
During the selection of the dominant follicle, mural granulosa produce low levels of _____ and ____ declines.
Midcycle, the dominant follicle becomes ____ dependent on _____ to continue growth until ovulation.
Estrogen and inhibin B; FSH levels decline; largest follicle with most FSH receptors becomes dominant follicle
Large preovulatory follicle (graffian follicle); LH and FSH
When is the preovulatory period and how long does it last?
What happens to the follicle?
Changes in steroidogenic fx of theca and mural granulosa do what?
Time from onset of LH surge to ovulation; 32-36 hours
Structural changes preparing for ovulation
Prepare cells for luteinization, formation of corpus luteum, increase production of progesterone
What drug treats infertility?
How?
What does increasing FSH do?
Clomiphene citrate: selective estrogen receptor modulator; interferes with estrogen negative feedback therefore increased FSH (used in artificial insemination)
Increase antral follicle development; multiple oocytes can be ovulated; ovulation triggered with LH or hCG to time ovulation with the reproductive technique
What infertility technique is followed by FSH treatment?
What do these agonists/antagonists do?
GnRH agonists or antagonists (used in IVF)
Prevent normal LH surge
FSH leads to development of multiple follicles
HGC trigger mimics LH surge to time egg collection
What does the LH surge during ovulation and luteinization do?
How does this affect thecal and mural granulosa cells?
How does this affect steroidogenic activity?
Induces differentiation/luteinization of granulosa cells to granulosa lutein cells
Begin to express LH receptors
Induces shift in steroidogenic activity to production of progesterone
Inhibits aromatase expression -> reduces estradiol’s feedback on LH secretion
Increases vascularization of granulosa -> increases cholesterol availability for progesterone production
What are the structural changes caused by the LH surge during ovulation and luteinization?
Breakdown of what?
What detaches?
Basal lamina?
Oocyte progresses to what?
Release of cytokines and hydrolytic enzymes from theca and granulosa cells -> breakdown follicle wall, tunica albuginea, surface epithelium
Cumulus-oocyte complex detaches (free floating in antrum)
Basal lamina of mural granulosa degraded -> angiogenic factors released -> increased blood supply to follicle/corpus luteum
Metaphase II
Ovulation and luteinization:
Increased size of follicle and position in cortex causes a ____ on ovarian surface.
Bulging stigma wall becomes thin and ____.
____ breaks down ruptures.
____, ____, and ____ flow out to peritoneal cavity.
___ sweep the cumulus mass into oviducal ostium
Bulge
Avascular
CT
Follicular fluid, oocyte, and surrounding cumulus cells
Fimbria
What happens in the luteal phase?
____ cells collapse into the antral cavity?
What else is in the antral cavity?
Antral cavity fills with blood/cell debris (corpus hemorrhagicum; removed by macrophages)
Granulosa lutein
Cholesterol esters (progesterone production) and theca, blood vessels, & WBC fill remainder of the cavity; yellow due to carotenoids pigment, lutein
What is the main fx of the follicle after ovulation?
How long does the corpus luteum of menstruation remain?
What does it become if there is no fertilization?
What happens to the corpus luteum if there is a pregnancy?
Produce progesterone
14 days
Corpus albicans (scar-like body, primarily collagen)
HCG will rescue it so it remains viable for the duration of the pregnancy so it will continue to produce progesterone
If the corpus luteum is stimulated by hCG, what does it produce?
What is the fx?
What hormone decreases following the LH surge?
What reduces LH to basal levels?
What do lutein cells secrete?
Progesterone
Transform uterine lining into adhesive and supportive structure for implantation and early pregnancy
Decrease in estrogen, rebounds and peaks mid luteal phase
Progesterone and estrogen (hCG compensates for the decline in LH)
Inhibin A: suppress FSH so more follicles don’t get released and ovulated
What happens during follicular atresia?
When does this happen?
What cells undergo apoptosis?
What cells persist and repopulate the cellular stoma of the ovary?
What do the thecal cells retain?
Demise of an ovarian follicle; predominant process in the ovary
Can occur at any time during development
Granulosa cells and oocytes undergo apoptosis
Thecal cells
LH receptors and ability to produce androgens -> interstitial gland of the ovary
