The Menstrual Cycle and Ovulation Flashcards
1
Q
What do thecal cells lack that allows them to produce androstenedione?
A
Similar to Leydig cells, but lack 17B (prevents testosterone from forming androstenedione in Leydig cells)
2
Q
What are granulosa cells similar to in males?
A
nurse Sertoli cells
3
Q
Why are cumulus cells released with the oocyte during ovulation?
A
Critical for oviduct to grab onto the oocyte
4
Q
What causes meiotic arrest in prophase I of oocytes?
A
stuck in prophase 1 of meiosis 1 d/t:
–>elevated cAMP levels
**have proteins to finish meiosis but cAMP maintains arrest until LH surge
5
Q
What stimulates completion of meiosis I in oocytes?
A
LH surge
6
Q
How long can an oocyte stay in the first meiotic arrest?
A
50 years
7
Q
When does meiosis I finish?
A
a few hours before ovulation
- ->expels 1st polar body
- ->produces MAPK to arrest at metaphase II
8
Q
What causes the second meiotic arrest in oocytes?
A
stuck in metaphase II d/t:
–>elevated levels of MAPK proteins
9
Q
When does meiosis II resume and complete?
A
at fertilization only
- ->rapidly degrades MAPK to finish
- ->expels 2nd polar body
10
Q
What is the functional unit of the ovary?
A
ovarian follicle
11
Q
What is the primordial follicle?
A
primary oocyte arrested in prophase I
–>surrounded by single layer of pregranulosa cells
**only release paracrine factors, not steroid hormones
12
Q
What represents the ovarian reserve?
A
primordial follicles
–>most undergo atresia
–>only 400-500 develop and ovulate over lifetime
13
Q
Describe the primary follicle
A
central primary oocyte surrounded by single layer of cuboidal granulosa cells
–>increase in size d/t increase in growth of primary oocyte
–>produce ZP 1-4 as zona pellucida forms
14
Q
Describe the secondary follicle
A
primary oocyte surrounded by 3-6 layers of granulosa cells
–>paracrine secretion induces stromal cells to form thecal cells
15
Q
Describe the orientation of thecal cells in the secondary follicle
A
theca interna: highly vascular
theca externa: fibrous capsule-like
16
Q
Describe changes that cause primary follicle to become secondary follicle
A
- Follicles move closer to inner medulla of ovary (where vasculature is) and release angiogenic factors
- ->develop 1-2 arterioles to generate vascular wreath around follicle
*Zona pellucida develops
17
Q
What receptors do granulosa cells express?
A
FSH receptors
–>paracrine factors for oocyte growth
18
Q
Do granulosa cells produce ovarian hormones in preantral follicles?
A
NO
19
Q
What are thecal cells analogous to?
A
Leydig cells
20
Q
What receptors do thecal cells express?
A
LH receptors
21
Q
What is the major product from thecal cells?
A
androstenedione
–>minimal during preantral follicular period
22
Q
What marks the beginning of the antral phase of follicular development?
A
appearance of antrum (space filled with fluid around oocyte)
23
Q
What does increase in follicular size during the antral phase depend on?
A
- increase in antral size
- volume of follicular fluid
- prolif of granulosa cells
24
Q
What is the dense mass of granulosa cells that surrounds the oocyte suspended in fluid?
A
cumulus oophorus
25
What are the 2 distinct populations of granulosa cells in the antral phase/
- mural granulosa (stratum)
- -->outer wall of follicle, highly steroidogenic
- cumulus cells (corona radiata)
- -->maintain gap and adhesion jxns with oocyte
- -->released during ovulation with oocyte
26
What subset of granulosa cells make up the outer wall of the follicle and are highly steroidogenic?
mural granulosa
27
What gonadotropins are antral follicles responsive to during the antral phase?
FSH and LH
28
What do theca interna cells do in response to LH during antral phase?
synthesize androgens from acetate and cholesterol
-->major: androstenedione
-->limited estrogen synthesis
29
What do granulosa cells do in response to FSH during antral phase?
convert androgens from thecal cells
-->aromatization of androgens to ESTROGEN
-->induce expression of LH receptors in late follicular phase
30
When does oocyte growth slow?
rapid in early stages of antral follicles
slows in larger follicles
31
What follicular stage does oocyte complete meiosis I at ovulation?
antral stage
-->oocyte secrete cell cycle components
-->larger antral follicles still maintain meiotic arrest (via elevated cAMP) until LH surge
32
What are the 3 phases of the ovarian follicle cycle?
1: follicular phase
- -->preantral and antral sub-phases
2: ovulatory phase
3: luteal phase
33
How does sensitivity to FSH aid in selection of the dominant follicle?
FSH declines due to mural granulosa cells producing low levels of estrogen and inhibin B
- ->largest follicle with most FSH receptors survives (becomes dominant)
- ->other follicles undergo atresia
34
Describe how a dominant follicle is chosen
Each monthly cycle, several large antral follicles are recruited to begin development
-->all undergo atresia except 1 d/t FSH decline
-->dominant follicle (usually largest with lots of FSH receptors) chosen in early follicular phase
35
What does the midcycle dominant follicle become?
Graffian follicle (large preovulatory follicle)
36
What is the periovulatory period?
onset of LH surge to ovulation
| -->32-36 hours
37
What is the fxn of the periovulatory period?
Prepare for ovulation:
- ->changes in steroidogenic fxn of theca and mural granulosa
* **prepare cell for luteinization
* **formation of corpus luteum
* ** increased production of progesterone
38
During the LH surge, what cells express LH receptors?
both thecal and mural granulosa cells
39
What reduces the positive feedback on LH secretion during the LH surge?
surge shifts steroidogenic activity so there is a transient inhibition of aromatase
- ->reduces positive feedback on LH
- ->switches production of estradiol to progesterone
40
When is there an increase in progesterone production?
after LH surge/ovulation
41
What is the consequence of increased vascularization of granulosa during LH surge?
increased cholesterol availability for progesterone production
42
LH surge induces oocytes to?
progress to metaphase II
| -->releases inhibition of the first meiotic arrest
43
How does the LH surge affect structural changes in the follicle?
LH surge + release of cytokines and hydrolytic enzymes
--> breakdown of follice, wall, tunica albuginea, surface epithelium
-->allows cumulus-oocyte complex to detach so it's free in the antrum
-->basal lamina of mural granulosa degradation to allow increased blood supply to corpus luteum (remainder of follicle without oocyte)
44
What is the corpus luteum?
the remainder of the follicle after the cumulus-oocyte complex has been emitted
45
What happens to the corpus luteum/follicle after the oocyte complex has been released?
antral cavity fills with RBC and debris
-->removed via macrophages
Granulosa lutein cells collapse into cavity
- ->filled with cholesterol esters (progesterone), thecal cells, WBC
- ->yellow in color d/t lutein pigment
46
How long is the corpus luteum programmed to survive for?
14 days
47
What happens when the corpus luteum is rescued by hCG?
will survive for remainder of pregnancy, main source of progesterone until placenta can take over
48
What happens to the corpus luteum after 14 days and no hCG/pregnancy?
forms a collagen scar-like body called the corpus albicans
-->regresses to inner medulla of ovary, absorbed
49
Why is progesterone from the corpus luteum important in early pregnancy?
transforms uterine lining into adhesive and supportive structure--> implantation
50
Describe estrogen increase/decrease following LH surge
Transient decrease following LH surge
Then rebounds and peaks in midluteal phase
51
What reduces LH to basal levels during pregnancy?
progesterone
estrogen
--compensation via hCG
52
What secretes inhibin A? What is its function?
Lutein cells
suppress FSH in pregnancy so not continuously ovulating when pregnant
53
Describe follicular atresia
Predominant process in ovary
-->occurs any time during development
*apoptosis of oocytes and granulosa cells
***thecal cells persist to repopulate cellular stroma of ovary
54
What are collectively known as interstitial gland of ovary?
Thecal cells with LH receptors
55
Describe the HP-ovarian axis
GnRH--> FSH and LH via gonadotrophs
FSH and LH + ovary to synthesize estrogens and progestins
56
Do ovarian steroids exert negative or positive feedback on the HPO axis?
both
57
Describe follicular response to GnRH
Early phase: gonadotrophs in pituitary not very responsive to GnRH
-->only small rise in LH
Late phase: very sensitive to GnRH--> larger release of LH
58
What does LH act on after ovulation?
Corpus luteum
59
What acts on the developing follicle before ovulation?
FSH and LH
- ->both required for estrogen production
- -->theca and granulosa cells can't finish production independently
60
What receptors do theca cells have?
LH
61
What receptors do granulosa cells have?
FSH
| some LH
62
What cell products inhibins?
granulosa cells of follicle
-->activated by FSH and during LH surge
**inhibits FSH production in anterior pituitary
63
What produces activins?
granulosa cells
***stimulate FSH from anterior pituitary
64
Describe negative feedback of HPO axis via ovarian steroids
Estrogens and progestins
-->reduce LH and FSH release
**progestins only negative at high concentrations
**estrogens negative at any concentration
65
Describe positive feedback of HPO axis via ovarian steroids
@ end of follicular phase
-->estradiol at certain level for 2 days causes HP axis to reverse sensitivity to estrogens
-->switch to positive feedback promotes LH SURGE
**progesterone late follicular phase also positive to help LH surge
66
Describe negative feedback by inhibits on HPO axis
inhibit FSH secretion
67
Describe positive feedback by activins on HPO axis
INDEPENDENT of GnRH
stimulate FSH release and ovarian synthesis of estrogens
68
Is GnRH required to help activins stimulate FSH release?
NO
69
What happens to FSH and LH as luteal phase of menstrual cycle begins?
rapidly decrease
-->negative feedback by estradiol, progesterone and inhibin (increase)
also causes ovarian steroid levels to drop
70
What is the relationship of LH and FSH to ovarian steroids during the start of the luteal phase?
FSH and LH drop
Estradiol, progesterone and inhibin increase
71
What leads to decreased ovarian steroids in late luteal phase?
demise of corpus luteum
72
What happens to GnRH during menses?
HP axis returns to follicular-phase pattern
-->gradual increase in pulsatile GnRH
73
What is the major product of the follicle during the follicular phase?
estradiol
-->aromatase, 17-20 and 17a absent
74
What is required for estradiol synthesis in follicle cells?
theca cells
| granulosa cells
75
What is required for estradiol synthesis in corpus luteum?
theca-lutein cells
granulosa-lutein cells
76
When are estrogens produced?
Follicular phase via follicles
Luteal phase via corpus luteum
77
What are the major products of the corpus lutem during the luteal phase?
progestins
-->estradiol still substantial
78
What does estrogen to to basal body temperature during the follicular phase of the menstrual cycle?
high levels of estrogen lower BBT
79
What hormone raises BBT?
Progesterone released by corpus luteum post-ovulation
-->day after ovulation
80
What does a drop in BBT coincide with?
no pregnancy and next menstruation cycle
-->d/t disintegration of corpus luteum
81
Describe the menstrual phase of the endometrial cycle
degeneration-->bleeding
-->defined as day 1 of menstrual cycle
**d/t degeneration of corpus luteum (no preg--> decreased estrogen and progesterone)
82
What is considered day 1 of menstrual cycle?
first day of bleeding/endometrial degeneration
83
Describe the proliferative phase of endometrial cycle
restored after day 5 of cycle
-->prolif of basal stromal cells in zona basalis
-->" of epithelial cells from uterus
-->stroma gives rise to CT components of endometrium
--> +++ by estrogen fri developing follicles
84
Describe estrogen levels in proliferative phase of endometrial cycle
rise early in follicular phase and peak just before ovulation
--> causes stromal components of endometrium to become highly developed
--> induces synthesis of progestin receptors in endometrial tissue
85
Describe the secretory phase of the endometrial cycle
Final phase that c/t luteal phase of ovarian cycle
- increase vasc of endometrium
- endometrial glands are engorged with secretions
PROGESTERONE:
-->promotes diff of stromal cells into predecidual cells--> decidua of pregnancy
OR
--> helps menstruation in absence of pregnancy
86
Describe the pathophysiology of PCOS
- most common cause of infertility
- adolescence
- unexplained hyperandrogenism, anovulation, polycystic ovary
* abnml steroidogenesis of ovary, folliculogenesis
87
Describe hormone levels in PCOS
Elevated LH
Low FSH
Elevated testosterone
Increased DHEA d/t enlarged polycystic ovaries
***high androgens promote atresia of developing follicles, disrupt feedback
88
What are presentations of PCOS females?
```
obese
young
hirsutism
reproductive age
oligomenorrhea
infertility
```
89
What is the most common cause of congenital hypogonasism?
Turner syndrome
-->complete absence of second X chromosome
90
Describe Turner syndrome
missing x chromosome
------>45 X
primary hypogonadism
female int/ext genitalia
ovarian failure
elevated serum FSH
91
What are common sx of Turner syndrome?
```
short stature
delayed puberty
infertility
webbed neck
lymphedema of
hands/feet
learning disabilities
skeletal abnml
```
92
Describe menopause
12 months after LMP
-->average 51 yrs
Reduction of estrogen and low levels of inhibin
-->no negative feedback of LH and FSH
High FSH and LH
93
What are sx of menopause?
```
irregular periods
vaginal dryness
hot flashes
night sweats
sleeping problems
mood changes
weight gain
slow metabolism
thinning hair
dry skin
lost of breast fullness
```
94
What are tmts for the sx of menopause?
- estrogen therapy
- vaginal estrogen
- low-dose antidepressants
- Gabapentin for hot flashes
95
What exert negative feedback to reduce LH and FSH?
estrogen
| progestins
