2-23-16-Female Reproductive Physiology (Lopez)

Question 1

Trace the stages of ovarian follicle maturation:

Answer 1

Primary oocyte (4N) –> Primordial follicle (4N) –> Primary follicle (4N) –> Secondary follicle (4N) –> Early tertiary follicle (4N) –> First mitotic division completed –> Graafian follicle (Has a secondary oocyte with 2N and 1st polar body with 2N) –> Beginning of 2nd meiotic division, fertilization, and completion of 2nd meiotic division –> Ovulated ovum

Question 2

___ represents the earliest and simplest follicular structure in the ovary, consists of the primary oocyte with a surrounding single layer of pregranulosa cells and has a basement membrane. It usually appears ~6 weeks into intrauterine life and the generation of these is complete by ~6 months after birth

Answer 2

Primordial follicle

Question 3

Growing primordial follicles restrain development of too many primordial follicles by release of ___

Answer 3

Anti-mullerian hormone (AMH)

Question 4

The gamete in primordial follicles is derived from oogonia that have entered the first meiotic division and are now called ___

Answer 4

Primary oocytes

Question 5

Primary oocytes progress through most of prophase I over a 2-week period and then arrest in the __ stage and the nucleus of the oocyte (germinal vesicle) remains intact at this stage

Answer 5

Diplotene

Question 6

One of the 1st visible signs of follicle growth is the appearance of cuboidal granulosa cells. At this point, the follicle is known as a __

Answer 6

Primary follicle –> contains a larger primary oocyte than the one in the primordial follicle

Question 7

As granulosa cells proliferate, they form a multilayered epithelium around the oocyte. At this point the follicle is known as ___

Answer 7

Secondary follicle –> contains a primary oocyte surrounded by several layers of cuboidal granulosa cells, have theca cells, and a zona pellucida

Question 8

The progression of secondary follicles involves the formation of ___ and an increase in __ to developing follicular units

Answer 8

Capillaries

Vascular supply

Question 9

The ___ provides a species-specific binding site for sperm during fertilization

Answer 9

Zona pellucida

Question 10

__ cells are analogous to testicular Leydig cells, the major product of which is androstenedione (opposed to testosterone in leydig cells)

Answer 10

Thecal

Question 11

Swelling of the antral cavity (as seen in a graafian follicle) increasingly divides granulosa cells into these 2 discrete populations:

Answer 11

1) Mural granulosa cells (stratum granulosum)

2) Cumulus cells (cumulus oophorus or corona radiata)

Question 12

Early antral follicles are dependent on __ for normal growth

Large antral follicles become highly dependent on __ for their growth and sustained variability

Answer 12

FSH

FSH

Question 13

___ form the outer wall of the follicle, are close to outerlying thecal cells, become highly steroidogenic, and remain in the ovary after ovulation to differentiate into the corpus luteum

Answer 13

Mural granulosa cells

Question 14

___ are inner cells surrounding the oocyte and the innermost layer (relative to the oocyte) of these cells maintains gap and adhesion junctions with the oocyte.

Answer 14

Cumulus cells

Question 15

During ovulation, ___ cells are released from the ovary with the oocyte and are crucial for the ability of the fimbriated end of the oviduct to grab and move the oocyte along the length of the oviduct to the site of fertilization

Answer 15

Cumulus

Question 16

At the antral stage, larger antral follicles gain meiotic competence but still maintain meiotic arrest until the midcycle ___ surge

Answer 16

LH

Question 17

Meiotic arrest during the antral stage is achieved by maintenance of elevated ___ levels in the mature oocyte

Answer 17

cAMP

Question 18

___ cells of large antral follicles produce significant amounts of androstenedione and testosterone (to a lesser extent)

Androgens are converted to estradiol-17-beta by the ___ cells

___ stimulates proliferation of granulosa cells and induces the expression of CYP19-aromatase

The mural granulosa cells of the large antral follicles produce increasing amounts of ___ during the early follicular phase

Answer 18

Thecal

Mural granulosa

FSH

Inhibin B

Question 19

Low levels of ___ exert a negative feedback effect on FSH secretion, thereby contributing to the selection of the follicle with the most FSH-responsive cells

Answer 19

Estrogen and inhibin

Question 20

As FSH levels decline, the rapidly growing follicles progressively undergo atresia, until __ follicle is left

The largest follicle with the most ___ receptors of the recruited crop becomes the dominant follicle

By midcycle, the dominant follicle becomes a large ___

Answer 20

1

FSH

Preovulatory follicle

Question 21

___ cells express LH receptors and produce androgens

___ cells express FSH receptors

Answer 21

Thecal –> basal LH levels stimulate production of steroidogenic enzymes (3beta-HSD, CYP17, CYP11A1), LDL receptors

Granulosa –> FSH up-regulates aromatase gene expression and activity which converts androstenedione to estrone and testosterone to estradiol-17-beta. They also express activating isoforms of 17beta-HSD

Question 22

___ induces expression of inhibin B during the follicular phase and also induces the expression of LH receptors in the mural granulosa cells during the 2nd half of the follicular phase

Answer 22

FSH

Question 23

___ period can be defined as the time from the onset of the LH surge to ovulation. It lasts 32-36 hours in women

Answer 23

Periovulatory

Question 24

Luteinization culminates in the formation of a ___, which is capable of producing large amounts of progesterone, along with estrogen, within a few days after ovulation

Answer 24

Corpus luteum

Question 25

The __ surge induces dramatic structural changes in the dominant follicle that involve its rupture, ovulation of the cumulus-oocyte complex, and the biogenesis of corpus luteum from the remaining thecal cells and mural granulosa cells

Answer 25

LH

Question 26

MAJOR STRUCTURAL CHANGES ASSOCIATED WITH LH SURGE: Before ovulation, the follicle presses against the wall of the ovary to form a bulge called the ___ __ cells detach from granulosa cells and the oocyte is freed within the antral cavity. As an indirect response to the LH surge, the oocyte releases TGF-beta and ___, which stimulates the cumulus cells to secrete hyaluronic acid and other ECM components which causes expansion of the oocyte complex, making it easier for capture by the oviduct and easier for sperm to locate The __ of the mural granulosa cells is then enzymatically degraded and blood vessels and outer-lying theca can push into the granulosa cells

Answer 26

Stigma Cumulus GDF9 Basal lamina

Question 27

Before ovulation, the primary oocyte is competent to complete meiosis but is arrested in prophase I as a result of high ___ levels ---> ___ induces release from arrest and completion of meiosis I with extrusion of the 1st polar body --> The secondary oocyte then progresses to ___ where it arrests again until fertilization

Answer 27

cAMP LH surge Metaphase II

Question 28

During the luteal phase, the major products of the corpus luteum are the __, although estradiol is still substantial

Answer 28

Progestins

Question 29

After ovulation, the antral cavitity fills with blood from ruptured vessels (corpus hemorrhagicum). The ___ is formed and the granulosa cells now become granulosa lutein cells which enlarge and fill with cholesterol esters. These cells collapse and fill in the antral cavity

Answer 29

Corpus luteum

Question 30

The LH surge induces these 2 parallel events:

Answer 30

Ovulation and Luteinization

Question 31

___ production by the corpus luteum increases steadily from the onset of the LH surge and peaks during the mid-luteal phase __ production transiently decreases in response to the LH surge but then rebounds and also peaks at mid-luteal phase Granulosa lutein cells secrete ___ which further suppresses FSH secretion

Answer 31

Progesterone Estrogen Inhibin A

Question 32

__ is the demise of an ovarian follicle, is the predominant process in the ovary, and can occur at any time during development

Answer 32

Follicular atresia

Question 33

During follicular atresia, ____ undergo apoptosis, while __ cells persist and re-populate the cellular stroma of the ovary

Answer 33

Granulosa cells and oocytes Thecal

Question 34

___ phase is associated with the recruitment/growth of antral follicles, selection of one dominant follicle, and growth of dominant follicle until ovulation

Answer 34

Follicular

Question 35

The LH surge is associated with ___

Answer 35

Ovulation

Question 36

___ phase is associated with hormonal secretion by the corpus luteum

Answer 36

Luteal

Question 37

Neurovascular elements run into the ___ of the ovary The ___ is the functional unit of the ovaryt

Answer 37

Medulla Ovarian follicle

Question 38

___ = beginning of menstrual cycles ___ = breast development ___ = increase in adrenal androgen secretion

Answer 38

Menarche Thelarche Adrenarche

Question 39

The follicular phase and luteal phase are associated with the ___ cycle Menses, proliferative phase, and secretory phase are associated with the ___ cycle

Answer 39

Ovarian Endometrial

Question 40

The follicular phase of the ovarian cycle coincides with the phase(s) of the endometrial cycle?

Answer 40

Proliferative phase (and most of menses)

Question 41

The luteal phase of the ovarian cycle coincides with what phase(s) of the endometrial cycle?

Answer 41

Secretory phase (small amount of menses)

Question 42

During follicular phase of the ovarian cycle: ___ stimulates a follicle to complete its development It begins with onset of menses and ends on day of ___ (~14 days) ___ cells of the follicles increase production of the estrogen estradiol, which stimulates the endometrium to undergo rapid and continuous growth and maturation Follicular phase coincides with the __ phase of the endometrial cycle

Answer 42

FSH LH surge Granulosa Secretory

Question 43

During the follicular phase of the ovarian cycle, a rapid rise in ovarian estradiol secretion eventually triggers a surge in ___, which causes ovulation

Answer 43

LH

Question 44

During luteal phase of the ovarian cycle: Follicle transforms into a ___ ___ cells produce progesterone and estrogen, which stimulate further endometrial growth and development Begins on day of LH surge and ends at onset of next ___ (~14 days) The luteal phase of the ovarian cycle coincides with the ___ phase of the endometrial cycle

Answer 44

Corpus luteum Luteal Menses Secretory

Question 45

Granulosa cells can secrete ___ which negatively feedsback on the AP but can also secrete ___ which positively feedsback on the AP

Answer 45

Inhibins Activins

Question 46

GnRH stimulates gonadotroph secretion of FSH and LH, which stimulates ovarian cells to secrete ___

Answer 46

Estrogens and progestins

Question 47

Which part of the follicular phase is there a much larger release of LH?

Answer 47

Later in the follicular phase--> gonadotrophs in the AP become much more sensitive to the GnRH in the portal blood, each burst of GnRH triggers a much larger release of LH

Question 48

Before ovulation, the LH and FSH secreted by the gonadotrophs act on cells of the developing follicle. --> ___ cells of the follicle have LH receptors ___ cells have both LH and FSH receptors

Answer 48

Theca Granulosa

Question 49

Both LH and FSH are required for ___ production because neither the theca cell nor the granulosa cell can carry out all of the required steps. After ovulation, LH acts on the cells of the ___

Answer 49

Estrogen Corpus luteum

Question 50

___ specifically stimulates the granulosa cells to produce inhibins Just before ovulation, after the granulosa cells acquire LH receptors, LH also stimulates production of ___ by granulosa cells Inhibins "inhibit" ___ production by gonadotrophs of the AP

Answer 50

FSH Inhibin FSH

Question 51

Ovarian steroids (estrogen and progesterone) exert positive feedback at the end of the __ phase

Answer 51

Follicular

Question 52

Levels of ___ rise gradually during the first half of the follicular phase of the ovarian cycle and then steeply during the second half

Answer 52

Estradiol

Question 53

When the HP axis reverses its sensitivity to estrogens during the latter half of the follicular phase, positive feedback will promote a surge of ___ and the rising levels of ___ during the late follicular phase also produce a positive feedback response and contribute to the surge of ___

Answer 53

LH Progesterone LH

Question 54

As the luteal phase of the menstrual cycle begins, circulating levels of ___ rapidly decrease and this fall-off in levels reflects negative feedback by estradiol, progesterone, and inhibin

Answer 54

LH and FSH

Question 55

During the luteal phase, the rise in concentration of ___ causes negative feedback on the release of LH and FSH (causes decreased secretion)

Answer 55

Estradiol, progesterone, and inhibin

Question 56

During the late luteal phase, the gradual demise of the __ leads to decreases in the levels of progesterone, estradiol, and inhibin.

Answer 56

Corpus luteum

Question 57

In a nonpregnant woma, estradiol, the primary circulating estrogen, is secreted principally by the __ Cells in the ovaries have an __ enzyme that can convert androstenedione to estrone and testosterone to estradiol Estrone can be converted into the more powerful estrogen estradiol, and vice-versa by the enzyme ___

Answer 57

Ovary Aromatase 17beta-HSD

Question 58

During the follicular phase, the major product of the follicle is ___

Answer 58

Estradiol

Question 59

In the follicular phase of the menstrual cycle, the ___ synthesizes estrogens, whereas in the luteal phase, the ___ synthesizes estrogens

Answer 59

Follicle Corpus luteum

Question 60

Estradiol synthesis requires the contribution of which 2 cell types?

Answer 60

Theca and granulosa cells within the follicle AND Theca-lutein and granulosa-lutein cells within the corpus luteum

Question 61

During the luteal phase, the major products of the corpus luteum are the ___

Answer 61

Progestins, although estradiol synthesis is still substantial

Question 62

The ___ hormones drive the morphological and functional changes of the endometrium during the monthly cycle

Answer 62

Ovarian

Question 63

The higher levels of estrogen present during the pre-ovulatory (follicular) phase of the menstrual cycle have what effect on basal body temperature? The higher levels of progesterone released by the corpus luteum after ovulation has what effect on basal body temperature?

Answer 63

Lowers the BBT Raise the BBT

Question 64

The disintegration of the corpus luteum (if pregnancy does not occur) has what effect on basal body temperature?

Answer 64

Lowers the BBT--> coincides with the onset of the next menstruation

Question 65

During the menstrual phase of the endometrial cycle: If the oocyte was not fertilized and pregnancy did not occur in the previous cycle, a sudden dimunition in ___ secretion will signal the demise of the corpus luteum

Answer 65

Estrogen and progesterone

Question 66

As hormonal support of the endometrium is withdrawn, the endometrium degenerates, the tissue breaks down, and menstrual bleeding ensues; this moment is defined as day __ of the menstrual cycle

Answer 66

1

Question 67

This phase of the endometrial cycle follows menstruation and the endometrium is restored by about the 5th day of the cycle

Answer 67

Proliferative phase

Question 68

During the proliferative phase of the endometrial cycle: Proliferation of the basal stromal cells occurs in the ___ Proliferation of epithelial cells from other parts of the ___ The __ gives rise to the connective tissue components of the endometrium Proliferation and differentiation of the endometrium are stimulated by ___, which is secreted by developing follicles Levels of ___ rise early in the follicular phase and peak just before ovulation. This hormone causes the stromal components of the endometrium to become highly developed and also induces the synthesis of progestin receptors in endometrial tissue ___ opposes the action of estrogen on the epithelial cells of the endometrium and functions as an anti-estrogen which inhibits epithelai cell proliferation but promotes proliferation of endometrial stroma. It also stimulates 17-beta-HSD and sulfotransferase

Answer 68

Zona basalis uterus Stroma Estrogen Estrogen Progesterone

Question 69

__ is the final phase of the endometrial cycle and corresponds to the luteal phase of the ovarian cycle

Answer 69

Secretory

Question 70

The early secretory phase of the endometrial cycle is stimulated by ___

Answer 70

Progesterone

Question 71

During the middle to late secretory phase of the endometrial cycle, vascularization of the endometrium increases, glycogen content increase, thickness of endometrium increases, and endometrial glands become engorged with secretions. Also, ___ promotes the differentiation of the stromal cells into predicidual cells, which must be prepared to form the decidua of pregnancy, or to orchestrate menstruation in the absence of pregnancy

Answer 71

Progesterone

Question 72

The net effect of oral contraceptive pills is suppressed secretion of ___

Answer 72

FSH and LH -Low FSH levels are insufficient to stimulate normal folliculogenesis, the low LH levels obviate the LH surge and therefore inhibit ovulation

Question 73

The progestin effect of the OCP causes the cervical mucus to __

Answer 73

Thicken, become sticky and insufficient--> inhibits sperm penetration into the uterus

Question 74

___ is a loss of > 80 mL of blood ___ is painful periods ___ is existence of few, irregular periods ___ is absence of periods

Answer 74

Menorrhagia Dysmenorrhea Oligomenorrhea Amenorrhea

Question 75

__ and __ are often due to dysfunction or cessation of the H-P-Ovarian axis, as opposed to local pelvic pathophysiology

Answer 75

Oligomenorrhea and amenorrhea

Question 76

___ most commonly affects women of reproductive age, is a common cause of female sterility, and is a painful disorder in which tissue that normally grows inside the uterus grows outside of it (presence of endometrial glands and stroma outside the uterus)

Answer 76

Endometriosis

Question 77

List the clinical presentation of endometriosis:

Answer 77

- chronic pelvic pain linked to menses - dymenorrhea - dyspareunia (painful sex) - rectal pain and constipation - infertility

Question 78

___ is the most common cause of infertility in women, frequently becomes manifest during adolescence. Part of this dysfunction is characterized by abnormal ovarian steroidogenesis and folliculogenesis that are manifested clinically by androgen excess and anovulation

Answer 78

Polycystic ovarian syndrome (PCOS)

Question 79

Enlarged polycystic ovaries are known to be associated with increased __ levels which promote atresia in developing follicles and disrupt feedback relationships

Answer 79

Androgen levels (DHEA) Presentation: young, obese, hirsute females of repro age; oligomenorrhea or secondary amenorrhea; infertility

Question 80

List the levels of LH, FSH, and testosterone in PCOS

Answer 80

Elevated LH, low FSH, elevated testosterone

Question 81

___ is the most common cause of congenital hypogonadism; in about 50% of cases, it results from the complete absence of the second X chromosome. Germ cells do not develop and each gonad consists of a CT-filled streak. A pt would present with short stature, webbed neck, low set ears, shield-shaped chest, short 4th metacarpals, and sexual infantilism

Answer 81

Turner syndrome

Question 82

``` Describe the levels of the following in menopause: Estrogen: ___ Inhibin: ___ Feedback status for LH and FSH:____ Levels of FSH and LH: ___ ```

Answer 82

Reduced estrogen Low levels of inhibin No negative feedback of FSH and LH High levels of LH and FSH

Question 83

What are treatment options for relieving signs and symptoms or preventing/managing chronic conditions that may occur with aging and menopause?

Answer 83

- estrogen therapy - vaginal estrogen - low-dose anti-depressants - gabapentin (treatment of hot flashes)