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GIGU Exam 2 > Menstrual Cycle And Ovulation > Flashcards

Menstrual Cycle And Ovulation Flashcards

1
Q

What are the phases of the ovarian cycle?

A

Follicular phase (development of follicles) and luteal phase (formation of the corpus luteum)

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2
Q

What are the stages of the endometrial cycle?

A

Menses
Proliferative phase
Secretory phase

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3
Q

Describe the meiosis that occurs throughout the ovarian cycle

A

Meiotic arrest (prophase 1)
-elevated levels of cAMP
-large antral follicles gain meiotic competence (stay in arrest until LH surge and can stay in this stage around 50 years)
Meiosis I finishes before ovulation (polar body 1 extruded)
Meiotic arrest (metaphase II)
-elevated levels of MAPK proteins
Resumption of meiosis II only occurs at fertilization
-rapid degeneration of MAPK
-polar body 2 extruded

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4
Q

What is the ovarian follicle?

A

Ovarian follicle: functional unit of the ovary
Performs gametogenic and endocrine functions
Pre-menopausal cycling ovary contains follicular structures at many different stages

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5
Q

What is a primordial follicle?

A

Primary oocyte arrested in first meiotic prophase
Surrounded by a single layer of pregranulosa cells
Release paracrine factors no steroid hormones
Represents the ovarian reserve of which most will undergo atresia (400-500 develop and ovulate)

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6
Q

What is the primary follicle?

A

Central primary oocyte
Single layer of granulosa cells taking a cuboidal shape
Increase in size of follicle due to growth of primary oocyte
Early production of secreted glycoproteins (ZP1-4)

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7
Q

What is the secondary follicle?

A

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
-inner glandular highly vascular theca interna
-fibrous capsule like theca externa

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8
Q

Describe the progression of the secondary follicle

A

Involves increased vascularization
Migration from outer cortex to inner cortex closer to ovarian vasculature
Follicles release angiogenic factors that induce development of 1-2 arterioles (generates vascular wreath around the follicle)
ZP development (provides binding sites for sperm during fertilization)

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9
Q

What are growing preantral follicles?

A

Minimal endocrine function
Granulosa cells express FSH receptors primarily dependent on paracrine factors from oocyte for growth
Granulosa cells dont produce ovarian hormones at this point
Thecal cells are analogous to testicular Leydig cells (express LH receptors and major product is androstenedione but is minimal)

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10
Q

Describe antral follicular development

A

The appearance of the antrum marks the beginning of the antral phase
Increase in follicular size depends on increase in antral size, volume of follicular fluid, proliferation of granulosa cells
Oocyte becomes suspended in fluid surrounded by a dense mass of granulosa cells (cumulus oophorus)

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11
Q

What is the antral phase?

A 
100 fold increase in granulosa cells (two distinct populations) 
Mural granulosa cells - outer wall of follicle and become highly steroidogenic 
Cumulus cells (cumulus oophorus/corona radiata): maintain gap and adhesion junctions with oocyte; released during ovulation with oocyte
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12
Q

Describe antral follicle growth

A

Growth at this stage becomes responsive to gonadotropins
Theca interna - LH
-synthesize androgens from acetate and cholesterol
-limited estrogen synthesis; androstenedione is major steroid product
Granulosa - FSH
-converts androgens form thecal cells
-granulosa mediated aromatization of androgens to estrogens
-stimulated by FSH
-induces expression of LH receptors late in follicular phase

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13
Q

Describe how antral follicle growth affects the oocyte

A

Oocyte grows rapidly in the early stages of antral follicles; growth then slows in larger follicles
At the antral stage the oocyte becomes competent to complete meiosis I at ovulation
The oocyte synthesizes sufficient amounts of cell cycle components
Larger antral follicles, gain meiotic competence, but still maintain meiotic arrest until the mid cycle LH surge
Meiotic arrest is achieved by the maintenance of elevated cAMP levels in the mature oocyte

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14
Q

How does sensitivity to FSH aid in selection?

A

Several large antral follicles are recruited to begin development each monthly cycle
Selection of 1 dominant follicle early in follicular phase
Mural granulosa cells produce low levels of estrogen and inhibin B
-FSH levels decline (largest follicle with most FSH receptors/highest sensitivity becomes the dominant follicle)
-others undergo atresia
Mid cycle dominant follicle becomes a large pre-ovulatory follicle (Graafian follicle)

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15
Q

What is the periovulatory period?

A

Defined as time from onset of LH surge to ovulation
About 32-36 hours
Structural changes occur for preparation for ovulation
Changes in steroidogenic function of theca and granulosa cells
-prepares cells for luteinization
-formation of CL
-increased production of progesterone

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16
Q

What does the LH surge cause?

A 
Induces differentiation (luteinization) of granulosa cells to granulosa lutein cells 
Induces structural changes
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17
Q

Describe the role the LH surge has on luteinization

A

Thecal and mural granulosa cells express LH receptors at surge
Induces shift in steroidogenic activity
Transient inhibition of aromatase Expression
-rapid decline reduces positive feedback on LH secretion
Increased vascularization of granulosa
-increased cholesterol availability for progesterone production

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18
Q

Describe the structural changes that occur during the LH surge

A

Release of cytokines and hydrolytic enzymes from Theca and granulosa
-breakdown of follicle wall, TA and 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
LH surge induces oocyte to progress to metaphase II

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19
Q

Describe the luteal phase

A

Antral cavity filled with blood/cell debris
-corpus hemorrhagicum
-debris removed by macrophages
Granulosa lutein cells collapse into antral cavity
-filled with cholesterol esters
-theca, blood vessels, WBCs fill remainder of cavity
-often yellow in color due to carotenoid pigment (lutein)

20
Q

What is the corpus luteum?

A

No pregnancy - CL of menstruation remains ~14 and when it regresses it becomes the corpus alibicans (scar like body and primarily collagen)
If rescued by hCG from conceptus it will remain visible for duration of pregnancy

21
Q

Describe the CL of pregnancy

A

Produces increasing progesterone
-transforms uterine lining into adhesive and supportive structure (important for implantation and early pregnancy)
Transient decrease in estrogen following LH surge, rebounds and peaks midluteal phase
Progesterone and estrogen reduce LH to basal levels (hCG compensates for this decline)
Lutein cells secrete inhibin A which suppresses FSH

22
Q

What is follicular atresia?

A

Demise of an ovarian follicle
Predominant process in the ovary
Can occur at any time during development
During atresia, the granulosa cells and oocytes undergo apoptosis
Thecal cells persist and repopulate the cellular stroma of the ovary
-thecal cells retain LH receptors and the ability to produce androgens; collectively are referred to as the intestinal gland of the ovary

23
Q

Describe the hypothalamic pituitary ovarian axis

A

GnRH causes pituitary to release FSH and LH which stimulate the ovary to synthesize and secrete estrogens and progestins
Ovaries also produce inhibin and activin peptides
Ovarian steroids exert both positive and negative feedback on both the hypothalamus and anterior pituitary

24
Q

Describe the pulsatile release of GnRH and pulsatile secretion of LH

A

GnRH released in rhythmic pulses
Early in the follicular phase gonadtrophins are not very GnRH sensitive
Each burst of GnRH elicits only a small rise in LH
Later in follicular phase gonadotropin in the anterior pit become more sensitive to GnRH in the portal blood
Each burst of GnRH triggers a much larger release in LH

25
Q

Describe the effects of FSH and LH before ovulation

A

LH and FSH act on cells of the developing follicle before ovulation
Theca cells have LH receptors whereas granulosa cells have both LH and FSH receptors
Both LH and FSH are required for estrogen production because neither theca cells nor granulosa cells can carry out all the required steps

26
Q

After ovulation LH acts on the cells of what?

A

The CL

27
Q

What are inhibins?

A

Produced by the granulosa cells of the follicle
FSH specifically stimulates the granulosa cells to produce inhibins
Just before ovulation after the granulosa cells acquire LH receptors LH stimulates the production of inhibin by granulosa cells
Inhibits inhibit FSH production by gonadotropins

28
Q

What are activins?

A

Produced in the same tissues at the inhibins but they stimulate FSH release from pit cells

29
Q

Describe the negative feedback that occurs on the HPA axis

A

Throughout most of the menstrual cycle estrogens and progestins feed back negatively on hypothalamus and pituitary
Net effect is to reduce LH and FSH release
Estrogens exert negative feedback at both low and high concentrations whereas the progestins are effective only at high concentrations

30
Q

Describe the positive feedback that occurs on the HPA axis

A

Ovarian steroids exert positive feedback at the end of the follicular phase
Levels of estradiol rise gradually during the 1st half of the follicular phase of ovarian cycle and steeply during 2nd half
After estradiol levels reach a certain threshold for a min of 2 days HP axis reverses its sensitivity to estrogens now exerting a positive feedback (switch to positive feedback promotes the LH surge*)
Rising levels of progesterone during the late follicular phase also produces a positive feedback response and thus facilitates the LH surge

31
Q

Describe the feedback effects of inhibins and activins

A

Negative feedback by inhibins - inhibit FSH secretion by the gonadotrophs of the ant pit
Positive feedback by the activins - stimulatory effect of activins of FSHS release is independent of GnRH action; intraovarian action of stimulating the synthesis of estrogens

32
Q

What is involved in the induction of the LH surge?

A

Positive feedback of estrogens, progesterins and activins

33
Q

As the luteal phase of the menstrual cycle phase begins circulating levels of which hormones rapidly decreases?

A

FSH and LH
This fall off in gonadotropin levels reflects negative feedback by estradiol, progesterone, and inhibin
As gonadotropin levels fall so do the levels of ovarian steroids

34
Q

During the luteal phase the rise in concentration of estradiol, progesterone and inhibin causes the continued decrease of what?

A

Gonadotropin levels midway through the luteal phase
During the late luteal phase the gradual demise of the CL leads to decreases in the levels of progesterone, estrogen and inhibin

35
Q

After the onset of menstruation the HP axis returns to what?

A

A follicular phase pattern of LH secretion (i.e. a gradual increase in the frequency of GnRH pulses)

36
Q

During the follicular phase the major product of the follicle is what?

A

Estradiol
CL does the synthesis during the luteal phase
Estradiol synthesis requires the contribution of 2 cell types - theca and granulosa cells within the follicle and the theca-lutein and granulosa-lutein cells within the CL

37
Q

What are the major products of the CL during the luteal phase?

A

Progestins

Estradiol synthesis is substantial as well

38
Q

Describe hormonal regulation of basal body temperature (BBT) during the menstrual cycle*

A

Higher levels of estrogen present during the pre-ovulatory (follicular) phase of the menstrual cycle lower BBT
Higher levels of progesterone released by the CL after ovulation raise BBT (the rise in temp can most commonly be seen the day after ovulation but this varies)
If pregnancy doesn’t occur the disintegration of the cL causes a drop in BBT that roughly coincides with the onset of the next menstruation

39
Q

What drives the morphological and functional changes of the endometrium?

A

Ovarian hormones (estrogen - proliferation and progesterone - secretory state)

40
Q

What is the menstrual phase of the endometrial cycle

A

Start of endometrial cycle
If the oocyte was not fertilized and pregnancy did not occur in the previous cycle a sudden diminution in estrogen and progesterone secretion signals the demise of the CL
As hormonal support of the endometrium is withdrawn the endometrium degenerates, tissue breaks down resulting in menstrual bleeding
This moment is defined as day 1 of the menstrual cycle

41
Q

Describe the proliferative phase of the endometrial cycle

A

After menstruation the endometrium is restored by 5th day of the cycle
Proliferation of basal stromal cells in the zona basalis and pithelial cells from other parts of the uterus
Stroma gives rise to the CT components of the endometrium
Proliferation and differentiation of the endometrium are stimulated by estrogen (secreted by developing)

42
Q

Describe the role of estrogen during the proliferative phase of the endometrial cycle

A

Levels of estrogen rise early in the follicular phase and peak just before ovulation
Estrogen causes the stromal components of the endometrium to become highly developed
Estrogen also induces the synthesis of progestin receptors in endometrial tissue

43
Q

Describe the secretory phase of the endometrial cycle

A

Final phase of the uterine cycle; corresponds to the luteal phase of the ovarian cycle

44
Q

What occurs during the middle to late secretory phase?

A

Vascularization of the endometrium increases, glycogen content increases
Endometrial glands become engorged with secretions
Progesterone promotes the differentiation of the stromal cells into predecidual cells which must be prepared to form the decidua of pregnancy or to orchestrate menstruation in the absence of pregnancy

45
Q

What is menopause?

A

Defined as occurring 12 months after the last menstrual period; marks the period of menstrual cycle
Occurs at 51.1 years of age (average)
Due to reduction in estrogen, low levels of inhibin
-no negative feedback of LH and FSH; therefore high levels of LH and FSH*
Can occur naturally, prematurely (premature ovarian failure), due to surgery, or as a result of chemotherapy

46
Q

In the months or years leading up to menopause (perimenopause), signs and sx can include what?

A

Irregular periods, vaginal dryness, hot flashes, night sweats, sleep problems, mood changes, weight gain and slowed metabolism, thinning hair and dry skin, loss of breast fullness

47
Q

Most menopause treatment focuses on what?

A

Relieving the signs and sx and preventing or managing chronic conditions that may occur with aging Such as estrogen therapy, vaginal estrogen, low-dose antidepressants, Gabapentin (for Tx of hot flashes), etc

GIGU Exam 2 (17 decks)

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