Exam 2 - Female Repro Endo

Question 1

Describe the anatomy of the female reproductive system and the basic functions

Answer 1

vagina - site of sperm deposition/birth canal
cervix - selective barrier
uterus:
(myometrium) - expulsion of fetus at birth / muscular layer
(endometrium) - site of embryo implantation / glandular layer
ovary - site of ooctye, estradiol, and progesterone production
fimbria - pick up oocyte from ovary
ampulla - site of fertilization
isthmus - involved in embryo transport to the uterus

Question 2

What are the two basic functions of the ovary? What are the two endocrine glands contained in the ovary?

Answer 2

functions:
- produce oocytes
- secretes hormones (estradiol and progesterone)

endocrine glands:
- follicle (contains developing oocytes)
- corpus luteum (derived from the follicle after ovulation)

Question 3

How are the timings of sperm production and oocyte/hormone production different?

Answer 3

sperm production is continuous, while oocyte release and hormone secretion is periodic

Question 4

Describe the basic structure of a follicle - what cells types are there?

Answer 4

follicle contains germ and somatic cells
germ cells: oocytes
somatic cells: granulosa and theca cells

Question 5

Describe the process of oogenesis, including the phases, names of the developing oocyte in each phase, and chromosome/chromatid count.

Answer 5

oogonium (46/46) undergo mitosis and become primary oocytes (46/92) prior to birth (females are born with primary oocytes)

primary oocytes (46/92) start meiosis 1 but arrest in prophase 1 until puberty

after puberty, every month a single primary oocyte will complete meiosis 1 just before ovulation becoming a secondary oocyte and a first polar body (23/46).
The secondary oocyte is ovulated and starts meiosis 2 before arresting in metaphase 2.

If the secondary oocyte is fertilized, it will complete meiosis 2 and become a mature ovum and a second polar body (23/23).

Question 6

What is the basic event that happens in meiosis 1 and meiosis 2?

Answer 6

meiosis 1: separation of homologous chromosomes, 46/92 –> 23/46
meiosis 2: separation of sister chromatids, 23/46 –> 23/23

Question 7

When do the two arrests in oogenesis occur? What causes the development to resume in each case?

Answer 7

primary oocytes arrest in prophase 1 of meiosis 1, and complete it just before ovulation of that individual oocyte (1each month from puberty to menopause)

an ovulated econdary oocyte arrests in metaphase 2 of meiosis 2, and complete it if the oocyte is fertilized

Question 8

Describe the follicular structures and what each structure looks like

Answer 8

primordial follicle - oocyte with one layer of granulosa precursors and an outer basal lamina
primary follicle - oocyte with one layer of true granulosa cells and an outer basal lamina
pre-antral follicle (secondary) - oocyte with multiple layers of granulosa cells, a basal lamina, and a layer of theca cells on the outside
antral/Graafian follicle - oocyte with many granulosa cells, a basal lamina, and many theca cells but the outermost layer called theca external cells

Question 9

What types of follicles do not have theca cells? What does this mean?

Answer 9

primordial and primary do not have theca cells, so they do not produce very much hormone

Question 10

What is the basic function of granulosa and theca cells?

Answer 10

granulosa - surround and nourish developing germ cells, role in hormone production
theca cells - role in hormone production

Question 11

Describe the location/function of the basal lamina vs the zona pellucia.

Answer 11

basal lamina - Between the theca and granulosa cells, not touching the oocyte itself. Extracellular matrix that is secreted by the basement membrane, only role is separating these cells.

zona pellucida - First layer outside of the oocyte, before any granulosa cells. The mucopolysaccharide layer that surrounds the plasma membrane of the oocyte.

Question 12

Granulosa cells that directly surround the oocyte inside the antrum of a Graafian follicle are called…

Answer 12

cumulus cells

Question 13

The outermost layer of granulosa cells before the basal lamina/theca cells are called the…

Answer 13

mural granulosa cells

Question 14

Just prior to ovulation, there is —– mature follicle(s) in the ovary.

Answer 14

1 - the dominant follicle

Question 15

Describe the pathway of estrogen biosynthesis

Answer 15

cholesterol uses LH and cholesterol side-chain cleavage to become pregnenolone

Pregnenolone either:
becomes progesterone and uses 17a-hydroxylase to become 17 OH progesterone
or uses 17a-hydroxylase to become 17 OH Pregnenolone

17 OH Progesterone —> Androstenedione
17 OH Pregnenolone —> DHEA —> Androstenediol or Androstenedione

Androstenedione can:
- use FSH to become estrogens
- become testosterone and use FSH to become estrogens

Question 16

What are the three estrogens and where do they mostly come from? What is the relative potency?

Answer 16

most potent = E2: estradiol, produced by granulosa cells
intermediate potency = E1: estrone, produced by peripheral conversion of adrenal androgens
least potent = E3: estriol, produced by the placenta

Question 17

What is important about estrone compared to estradiol?

Answer 17

it is produced in small amounts, but it is the only estrogen produced after menopause

Question 18

How do LH and FSH stimulate hormone production? What types of cells are involved, and how do they each work?

Answer 18

LH binds to the theca cell -
- activate cAMP to turn cholesterol to pregnenolone
- pregnenolone uses 17a-hydroxylase to become androstenedione
-androstenedione diffuses across the basal lamina to the granulosa cells

• in the granulosa cell, androstenedione becomes testosterone
• FSH binds to granulosa cells, activates cAMP production of aromatase to turn testosterone into estradiol
• cAMP also makes inhibin

Question 19

In regards to theca and granulosa cells, what stimulates them, what do they produce, and what cells do they mimic in the male reproductive system?

Answer 19

theca - stim. by LH, produce androgens, analogous to Leydig cells

granulosa - stim. by FSH, produce estradiol, analogous to Sertoli cells

Question 20

Late in the follicular phase, the granulosa cells experience elevated estradiol and FSH that stimulate…

Answer 20

development of LH receptors in preparation for ovulation

Question 21

What are the three phases of the ovarian cycle?

Answer 21

follicular phase, ovulation, and luteal phase

Question 22

After oogonia undergo mitosis, what happens next in the fetal ovary (during gestation)?

Answer 22

• by 20 weeks gestation, some oogonia are surrounded by a single layer of granulosa cells to form primordial follicles
• any that do not become a primordial follicle degenerate before birth
• primordial follicles form the reservoir from which all oocytes in adult females arise
• the oogonia within primordial follicles begin and arrest in meiosis 1 (firing primary oocytes) prior to birth and remain in this state until the individual follicle is recruited for ovulation (anywhere from 13-50 years)

Question 23

Starting at birth and ending at puberty, what generally occurs in the ovary?

Answer 23

• the pool of primordial follicles gives rise to a continuous trickle of developing follicles
• prior to puberty, all developing follicles and oocytes within them undergo atresia
• after puberty, one follicle will reach maturity and be ovulated while all others undergo atresia

Question 24

What is the average cohort of follicles per cycle for a 20 year old female vs a 40 year old female?

Answer 24

20Y: 10-20 follicles
40Y: 4-5 follicles

Question 25

Is the signal to recruit follicles gonadotropin dependent?

Answer 25

No - independent of gonadotropin

Question 26

What happens as a follicle develops into the small antral stage? Are the changes gonadotropin dependent?

Answer 26

gonadotropin dependent changes form a zona pellucida, granulosa cells proliferate, and theca cells start to differentiate outside the basal lamina

Question 27

What happens as a follicle develops into the antral stage? Are the changes gonadotropin dependent?

Answer 27

gonadotropin dependent changes theca and granulosa cells become capable of estradiol synthesis and secretion, theca cells express LH receptors and granulosa express FSH receptors, estradiol is secreted into the antrum which then enters the systemic circulation and can affect other tissues

Question 28

What happens during the selection phase of follicle development?

Answer 28

- the mature/Graafian follicle (generally only 1) bulges from the ovary - follicle may be 15-20 mm in diameter - elevated estradiol induces expression of LH receptors on granulosa cells in preparation for ovulation

Question 29

What final change takes place to prepare for ovulation? How is this change/ovulation timed?

Answer 29

prostaglandins, collagenases, and proteases break down the wall of the ovary timing is coordinated with oocyte development

Question 30

What signal triggers ovulation? What 3 major changes take place as a result?

Answer 30

LH surge triggers ovulation - stimulates follicular prostaglandin production - stimulates differentiation of theca and granulosa cells into luteal cells - reinitiates meiosis of the oocyte (complete M1 and start M2, produce first polar body)

Question 31

After the follicle ruptures and releases the oocyte, the ovulated oocyte is surrounded by what?

Answer 31

cumulus cells (derived from granulosa cells)

Question 32

At what point do follicles become dependent on gonadotropin stimulation for their growth and development?

Answer 32

Once they become antral

Question 33

At what point does selection start occurring and some follicles undergo atresia?

Answer 33

starting on cycle day 1 (menses), when follicles are considered large antral follicles

Question 34

What produces AMH in the female reproductive system?

Answer 34

primary (pre-antral) follicles, secondary (pre-antral) follicles, and small antral follicles

Question 35

What types of follicles do NOT produce AMH?

Answer 35

primordial and large antral

Question 36

What happens to AMH production with age? What do high and low levels of AMH indicate?

Answer 36

AMH decreases with age because follicular reserve/recruitment decreases and runs out Low AMH - low follicle recruitment, low fertility or infertile High AMH - PCOS, follicles get stuck in pre-antral stages and do not develop, instead they build up and produce more AMH

Question 37

What is the approximate number of eggs at various life stages?

Answer 37

mid-gestation: 6-7 million oogonia birth: 2 million primary oocytes puberty: 400,000 primary oocytes menopause: 0

Question 38

What causes the decline in the number of eggs from mid-gestation to birth?

Answer 38

they undergo atresia if they don't get covered in a layer of granulosa cells to become primordial

Question 39

What is the average number of oocytes ovulated in a lifetime? These are the only oocytes to undergo.... Only ----- oocytes undergo meiosis 2.

Answer 39

450, these are the only ones to undergo all of meiosis 1. Only fertilized oocytes undergo meiosis 2.

Question 40

If a 20 year old woman is taking birth control pills or does not ovulate for some other reason, how many follicles are recruited each month?

Answer 40

10-20 Recruitment happens no matter what, can't be controlled and is not FSH/LH dependent, they will just all undergo atresia

Question 41

What happens to the remaining follicle after it ruptures during ovulation?

Answer 41

luteinization to form the corpus luteum: - theca and granulosa cells differentiate into luteal cells that express LH receptors - LH stimulates progesterone synthesis and secretion - progesterone secretion increases as the size of the corpus luteum increases

Question 42

Luteinized cells (theca lutein and granulosa lutein cells) have what changes to enzyme activity? What effect does this have on hormone production?

Answer 42

increases SCC enzyme activity decreased 17a-hydroxylase activity decreased aromatase activity 20x more progesterone than estradiol

Question 43

How do the cells in the corpus luteum work together to produce progesterone (and some estradiol)?

Answer 43

In both the theca lutein and granulosa lutein cells: LH stimulates cAMP to produce elevated SCC, converting more cholesterol to pregnenolone, which then converts to PROGESTERONE In the theca lutein cells... Less 17a-hydroxylase converts only some progesterone to androstenedione - diffuses over to granulosa lutein cells, becomes testosterone lower FSH triggers less cAMP to produce less aromatase - converts only some testosterone to estradiol

Question 44

How can you tell the difference between a follicle and the corpus luteum on ultrasound?

Answer 44

corpus luteum is less fluid, so it shows up as a solid structure/lighter color the follicle has lots of fluid in the antrum so it appears dark

Question 45

How does the endometrium change in response to elevated progesterone from the corpus luteum? How does this change the ultrasound image?

Answer 45

increased vascularization, glycogen content, epithelial cell endoplasmic reticulum, and mitochondria content creates a hazy endometrium on ultrasound

Question 46

What happens to the corpus luteum if a woman is not pregnant?

Answer 46

LH (a luteotropin) stimulates CL growth and biosynthesis in nonpregnant women the CL functions for 14 days and then undergoes luteolysis (programmed degeneration of the luteal cells)

Question 47

What happens to the corpus luteum if a woman is pregnant?

Answer 47

hCG is released after implantation, which stimulates CL growth and steroid biosynthesis until the placenta takes over

Question 48

If a female patient has a 17a-hydroxylase deficiency, they may...

Answer 48

have decrease synthesis of androgens and estrogen (not progesterone, 17a-hydroxylase is not needed for that)

Question 49

What are the two patterns of regulation of ovarian function, and what are their basic components?

Answer 49

Tonic (basal) LH secretion: regulates ovarian steroidogenesis via negative feedback, including follicular estradiol secretion and luteal progesterone/estradiol LH surge: regulates ovulation via positive feedback that is triggered by a sustained, elevated estradiol

Question 50

Describe the process of tonic (basal) LH secretion

Answer 50

GnRH release is pulsatile In the follicular phase estradiol > progesterone In the luteal phase progesterone > estradiol Both have negative feedback on the hypothalamus via ARCKiss1 neurons

Question 51

How does kisspeptin stimulate the adult reproductive axis in tonic (basal) regulation?

Answer 51

high levels of estrogens are sensed, suppressing the Kiss1 neurons, which suppresses the GnRH neurons, and causes less release of GnRH/LH/FSH

Question 52

Why does estrogen's negative feedback have to use the Kisspeptin route instead of directly contacting the GnRH neurons?

Answer 52

GnRH neurons don't have classic estrogen receptors, but Kiss1 neurons do, and GnRH neurons have kisspeptin receptors called GPR54

Question 53

When a female is menopausal, what happens to LH and FSH levels?

Answer 53

they increase (no ovarian estrogen production, no negative feedback, increase kiss stimulation, increase GnRH, increase LH/FSH)

Question 54

Describe the LH surge/how Kisspeptin functions in the reproductive axis for this process.

Answer 54

When estradiol levels are elevated for a sustained amount of time, they have positive feedback on the hypothalamus via APVP Kiss1 neurons really high estradoil will stimulate the AVPV Kiss1 neurons to stimulate more GnRH neurons, releasing more GnRH and more FSH/LH

Question 55

Do the AVPV and ARC Kiss1 neurons function at the same time or separate times? Explain.

Answer 55

they can both be functioning at the same time, but when estradiol gets really high the AVPV neurons (the gas pedal) override the ARC neurons (the brake) and there is a net increase in stimulation

Question 56

Why is the AVPV vs. ARC pathway unique between females and males?

Answer 56

AVPV is sexually dimorphic, meaning females have a 25 greater Kiss1 neurons than males, so they in turn have more AVPV neurons. This produces the sex-specific ability to have an LH surge (that males do not have)

Question 57

When estradiol gets really high, what TWO changes happen that contribute to increase FSH and LH?

Answer 57

the anterior pituitary gonadotropes increase in sensitivity to GnRH (same amounts of GnRH will produce more FSH and LH) the hypothalamus increases the pulses of GnRH secretion (more GnRH released overall)

Question 58

GnRH must be ----- for the maintenance of gonadotropin secretion. In what circumstance is LH or FSH favored?

Answer 58

must be pulsatile fast: favors LH slow: favors FSH

Question 59

Describe the study by Wildt on monkeys.

Answer 59

ovariectomized female rhesus monkeys with hypothalamic lesions delivered 1 pulse of GnRH per hour Each GnRH pulse was followed by an LH and FSH peak Increasing the frequency increased LH but decreased FSH, while lowering the frequency increased FSH and decreased LH

Question 60

What changes does the LH surge cause?

Answer 60

reinitiates meiotic division (finish meiosis 1 and start meiosis 2, stopping at metaphase 2) stimulate follicular prostaglandin production stimulate differentiation of theca and granulosa cells into theca lutein and granulosa lutein cells (all having LH receptors)

Question 61

Females with PCOS have higher GnRH pulse frequency. What impact does this have?

Answer 61

favors LH over FSH, so estrogen secretion lowers and androgen secretion increases

Question 62

What are the three phases of the ovarian cycle and how many days do they last?

Answer 62

follicular (1-14, variable) ovulatory (day 14) luteal (15-28, must be 14 days long)

Question 63

Describe the follicular phase of the ovarian cycle

Answer 63

a cohort of follicles starts to develop FSH stimulates the development of antral follicles and estradiol On Day 6 - one follicle becomes dominant and others undergo atresia Right before ovulation, granulosa cells express LH and FSH receptors

Question 64

Describe the ovulatory and luteal phases of the ovarian cycle

Answer 64

ovulatory - LH surge stimulates ovulation of the mature follicle within 24-36 hours luteal - corpus luteum forms and then degenerates in non-pregnant females

Question 65

Describe the phases of the uterine cycle

Answer 65

menstrual - shedding first day of menstruation is day 1 menses is the discharge of blood and endometrial tissue proliferative - growth estradiol stimulates the hyperplasia (growth) of epithelial cells secretory - prep for possible implantation progesterone stimulates vascularization, glycogen production, and increased epithelial endoplasmic reticulum/mitochondria

Question 66

Describe the hormonal regulation of estradiol in the follicular phase

Answer 66

Negative feedback: antral follicles secrete estradiol (and inhibin, both have suppress FSH) suppression of FSH contributes to atresia of smaller follicles low progesterone permits the rise of LH Positive feedback: rapid rise in estradiol, prepares body for fertilization, precedes the LH surge by 9-24 hours

Question 67

What is the overall action of the LH surge? Why is the FSH surge so small?

Answer 67

converts follicle from estradiol to a primarily progesterone secreting tissue inhibin diminishes the rise in FSH, so it is a smaller surge

Question 68

How does an ovulation predictor kit work?

Answer 68

detects the LH in urine, start testing prior to expected LH surge, two lines indicate surge and the beginning of ovulation

Question 69

Describe the hormonal regulation happening in the luteal phase

Answer 69

progesterone (and some estradiol) has negative feedback on LH and FSH Corpus luteum secretes progesterone, which prepares the endometrium for implantation (triggers the secretion phase of the uterine cycle) Luteolysis occurs 10-11 days after ovulation if implantation does not happen Luteolysis results in a decline in progesterone, permitting a rise in LH and FSH Prostaglandins aid in menses

Question 70

Why must the luteal phase be at least 14 days?

Answer 70

the embryo needs enough time to fully implant before the corpus luteum starts luteolysis and causes the endometrium to start shedding

Question 71

What contributes to the thickness vs. the vascularization of the endometrium?

Answer 71

thickness - estrogen released during the follicular phase vascularization - progesterone released from the corpus luteum in the luteal phase

Question 72

Describe the changes in cervical mucus throughout the menstrual cycle

Answer 72

early cycle - sticky but minimal, low E and P nearing ovulation - thinner, rising E and low P at ovulation - thin and watery, high E and low P right after ovulation - thick and sticky, low E and rising P

Question 73

How does cervical mucus impact sperm movement? What are the general trends in how E and P affect cervical mucus?

Answer 73

thin watery secretions facilitate the movement of sperm while thick and sticky secretions don't high estrogen (from follicles) causes thinner mucus high progesterone (from corpus luteum) and low estrogen cause thicker mucus

Question 74

What is the name for using cervical secretions to monitor fertility?

Answer 74

Billings Ovulation Method

Question 75

What are the general trends in basal body temp during the menstrual cycle?

Answer 75

rises after ovulation in parallel with progesterone from the corpus luteum, then drops when the corpus luteum degenerates and progesterone goes back down

Question 76

What happens to the cervical mucus of a female who has had her ovaries removed?

Answer 76

there won't be much - progesterone makes it thick (but there's no progesterone since she isn't ovulating or making a corpus luteum), and estrogen makes it thin (but there isn't estrogen from follicles) so there just isn't much at all.

Question 77

Besides the ovaries, where else are estrogen and progesterone made?

Answer 77

small amount of estrogen from adipose tissues, no other producer of progesterone

Question 78

Describe amenorrhea and anovulation

Answer 78

amenorrhea - failure to have menstrual cycles, primary (absence in a woman who has never menstruated, such as Turner's syndrome XO chromosomes with no ovaries or testes) or secondary (cessation in a woman who has menstruated previously, for various reasons) anovulation - ovulation doesn't occur, generally associated with amenorrhea

Question 79

Describe menstrual dysfunctions besides amenorrhea/anovulation

Answer 79

dysmenorrhea - painful menstrual cramps, overproduction of prostaglandins menorrhagia - heavy or prolonged periods, needing to change tampon/pad less than 2 hours or clots the size of a quarter endometriosis - cyclic growth of endometrial cells outside the uterus, can cause pain and infertility luteal phase defect - short luteal phase, less than 14 days can cause infertility