Reproduction 3: Female Repro/Menstrual Cycle Flashcards

1
Q

What is the fundamental reproductive unit of the female repro system?

A

Gonad = ovary, follicle is the primary reproductive unit

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2
Q

What is included in the female reproductive system?

A

oviducts, uterus, cervix, vagina, external genitalia

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3
Q

What is the internal genitalia derived from

A

mullerian ducts

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4
Q

GnRH is activated at puberty. What activates it?

A

Kisspeptin

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5
Q

What promotes secondary sex characteristics?

A

increased GnRH pulsatility during REM sleep

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6
Q

What stimulates pulsatile release of gonadotropins?

A

GnRH

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7
Q

What is the differential levels of GnRH at different stages of life?

A

spikes in fetal and infant development

low during childhood

elevated at night during puberty

elevated spikes during reproductive years

constantly high in menopause due to lack of neg feedback

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8
Q

The menstrual cycle causes physiological changes in what two organs?

A

ovary and uterus

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9
Q

What are the cycles called for the ovary and uterus respectively?

A

ovary: ovarian cycle
uterus: endometrial cycle

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10
Q

What causes the monthly menstrual pattern?

A

HPG axis feedback

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11
Q

Discuss the female HPG Axis

A

hypothalamus releases GnRH

GnRH stimulates anterior pituitary to release LH and FSH

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12
Q

What does FSH target?

A

Granulosa cells

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13
Q

What does LH target?

A

Theca cells and granulosa cells

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14
Q

What do theca cells do?

A

produce progestins and androgens

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15
Q

What do granulosa cells do?

A

produce progestins, estrogens, inhibins, and activins

converts androgen precursors to estradiol

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16
Q

What does FSH do?

A

stimulates follicular development and conversion of androgen precursors to estradiol

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17
Q

What does LH do?

A

stimulates biosynthesis of estrogens, induces ovulation and luteinization

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18
Q

When is LH higher than FSH?

A

reproductive years

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19
Q

What do theca cell do and what kind of receptors do they have?

A

produce androgens and progestin

receptors for LH

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20
Q

What do granulosa cells do and what kind of receptors do they have?

A

produce estrogens, progestins, inhibins, activins

receptors for LH and FSH

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21
Q

What kind of feedback do estrogens have?

A

negative and positive!

positive important for ovulation

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22
Q

What are the three phases of the ovarian cycle?

A

Follicular phase
Ovulatory phase
Luteal phase

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23
Q

What happens in the follicular phase?

A

Growth of dominant follicle

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24
Q

What happens in the ovulatory phase?

A

Follicle rupture and release of oocyte

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25
Q

What happens in the luteal phase?

A

Formation of corpus luteum

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26
Q

What are the three phases of the endometrial (uterine) phase

A

Menstrual phase
Proliferative phase
Secretory phase

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27
Q

What do HPG hormones do?

A

drive coordinated physiological changes during the menstrual cycle

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28
Q

What do physiological changes do?

A

Signal the hypothalamus

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29
Q

When does the proliferative phase occur?

A

coincident with majority of follicular phase of ovary

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30
Q

When does the secretory phase occur?

A

coincident with luteal phase of ovary

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31
Q

What occurs during the menstrual phase?

A

Endometrial shedding

coincident with early follicular phase of ovary

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32
Q

How long is the follicular phase?

A

variable, 10-14 days

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33
Q

How long is the ovulatory phase?

A

1-3 days

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34
Q

How long is the luteal phase?

A

14 days

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35
Q

Describe the stages of a follicle as it passes through the ovarian cycle

A

primordial follicle -> primary follicle -> secondary follicle -> mature (Graafian) follicle -> (ovulation/follicular rupture) -> corpora lutea -> corpus albicans -> atretic follicle

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36
Q

How do the L and R ovaries coordinate?

A

Alternate between ovaries every month/cycle. If both go through the cycle at the same time you can get dizygotic twins

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37
Q

When do the number of primordial follicles peak? How many are left at puberty?

A

Peak at 20 wks gestation. Only 10% left at puberty

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38
Q

What is a follicle?

A

one oocyte surrounded by a cluster of granulosa cells (germ cell surrounded by endocrine cells)

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39
Q

What does the mature ovary do?

A

maintain and nurture resident oocyte

mature oocyte and release it at the appropriate time

prepare vagina and fallopian tubes for fertilization

prepare the uterine lining to accept and implant a zygote

maintain hormonal support for the fetus until the endometrium is ready to do so

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40
Q

In the ovarian cycle, what does day 1 signify?

A

the first day of menses

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41
Q

What is a primordial follicle?

A

outer layer of pregranulosa cells plus a small oocyte

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42
Q

What stage are oocytes arrested in?

A

diplotene stage of prophase

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43
Q

What is a primary follicle?

A

Larger oocyte surrounded by cuboidal granulosa cells

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44
Q

What is required for the follicle to progress from the primordial to primary stage, and where does this happen?

A

Requires FSH, can happen in utero

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45
Q

What happens in a secondary follicle?

A

differentiation of stromal cells into theca cells

increased number of granulosa cells that become multilayered

enlargement of oocyte

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46
Q

What happens in a tertiary follicle, and what else is it called?

A

Early antral follicle

granulosa cells secrete fluid and create antrum

Granulosa cells closest to oocyte secrete
mucopolysaccharides – forms zona pellucida

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47
Q

How long does it take to mature from a primary to a mature graafian follicle?

A

10-14 days

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48
Q

What is the selection of a dominant follicle based on?

A

sensitivity to FSH and local paracrine actions of AMH produced by granulosa cells

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49
Q

What iss a graafian follicle?

A

the dominant follicle

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50
Q

What 3 types do granulosa cells stratify to?

A

mural cells
cumulus
antral

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51
Q

What do mural cells do?

A

farthest from oocyte
highest number of LH receptors
most metabolically active

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52
Q

What are the cumulus cells?

A

near oocyte, shed at ovulation

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53
Q

What are the antral cells?

A

face antrum, become luteal cells at ovulation

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54
Q

The oocyte is still a primary oocyte, arrested in diplotene stage until what occurs?

A

the LH surge

55
Q

What is a graafian follicle characterized by?

A

enlargement of the antrum presence of cumulus oophorous

56
Q

What kind of gland is the ovary?

A

a primary endocrine gland - it has no ducts to convey gametes to the uterus

57
Q

When is FSH high?

A

at the end of the ovarian cycle

58
Q

What does high FSH do?

A

recruits new cohort of follicles to enter the follicular phase

59
Q

What do recruited follicles produce, and what does it do?

A

produce inhibin B, which has a negative feedback on FSH

60
Q

What is important about low FSH?

A

only the follicle that is most sensitive to FSH will survive

61
Q

What happens when there is more LH than FSH?

A

stimulates steroid generation by theca cells

62
Q

How does inhibin B influence theca cells?

A

has a positive paracrine effect to augment steroidogenesis

63
Q

When does increased GnRH stimulate high levels of FSH and LH release from the anterior pituitary?

A

mid cycle - ovulation

64
Q

What activity does estrogen have on the pituitary during the follicular phase?

A

negative

65
Q

What feedback does estrogen have on the pituitary during ovulation/

A

(strong) positive

66
Q

what feedback does estrogen have on the pituitary during the luteal phase?

A

negative

67
Q

what activity does progesterone have during the luteal phase?

A

inhibits the pulse generator

68
Q

what do growing follicles produce?

A

increasing amounts of estrogen

69
Q

What effect does E2 feedback have on the anterior pituitary during the follicular phase?

A

favors LH over FSH (high frequency, low amplitude pulses)

70
Q

What receptors do theca cells have, and what do they produce?

A

LH –> synthesize androgens

71
Q

What kind of receptors do granulosa cells have?

A

LH and FSH

72
Q

What does FSH do in granulosa cells?

A

increases number of receptors for LH (responsible for LH surge)

increases aromatase (Cyp19) expression –> converts androgens to E2

73
Q

What is the two compartment theory of E2 synthesis?

A

Thecal cells produce androstenedione from cholesterol, which is transported to granulosa cells nd converted to E2

74
Q

What are the two main events during the ovulatory phase?

A

LH surge and ovulation

75
Q

What happens during the LH surge?

A

switch from negative to positive feedback

Follicle continues to mature

oocyte completes meiosis I and begins meiosis II

76
Q

Where is the secondary oocyte arrested during the ovulatory phase, and what allows it to progress?

A

metaphase II - meosis will complete upon fertilization

77
Q

What happens during ovulation?

A

expulsion of oocyte-cumulus complex out of ovary

increased inflammatory cytokines

breakdown of ovarian wall

78
Q

What is the positive feedback during ovulation?

A

increased E2 leads to increased LH, which leads to more E2, etc.

79
Q

What does increased E2 do?

A

E2 increases progesterone receptors

80
Q

What will cause a decrease in E2 and break the cycle?

A

rupture of the follicle

81
Q

what will decrease as a result of lower E2?

A

LH

82
Q

What are the three steps of follicle maturation?

A

cumulus cell expansion: forms corona radiata and cumulus oophorus

detachment of oocyte-cumulus complex - free floating in antrum

follicle forms bulge against ovarian wall (stigma)

83
Q

what is an oocyte that has completed meiosis I and is arrested in meiosis II?

A

a secondary oocyte + a polar body

84
Q

What is ovulation?

A

rupture of ovarian wall and extrusion of cumulus-oocyte complex

85
Q

What occurs after extrusion of the cumulus-oocyte complex?

A

differentiation of mural granulosa cells into large luteal cells and theca cells into small luteal cells

86
Q

What is the corpus luteum?

A

remnant follicle

87
Q

What is the major hormone product during the luteal phase?

A

progesterone, lesser amounts of E2

88
Q

during the luteal phase, what does the follicle no longer produce, and what is the effect?

A

follicle no longer produces inhibin B, and thus less negative feedback on FSH

89
Q

What inhibin predominates during the luteal phase, and what produces it?

A

Inhibin A (does not inhibit FSH), produced by the corpus luteum

90
Q

What are the hormonal effects on the HPG axis during the luteal phase?

A

high progesterone and E2 decrease GnRH, LH, and FSH

91
Q

What happens to the corpus luteum in the presence of low LH?

A

it is degraded

92
Q

How can the corpus luteum be rescued?

A

LH equivalent (hCG) produced by the implanted fertilized embryo

93
Q

What does the absence of HCG and LH cause?

A

decrease in E2 and progesterone, degradation of endometrium, beginning of menses

94
Q

What occurs at the end of the ovarian cycle?

A

death of the corpus luteum and drop in estrogen and progesterone levels

95
Q

What responds to falling P and E levels, and what does it do in response?

A

Pituitary responds to falling E and P by increasing FSH secretion

96
Q

What does an increase in FSH secretion cause?

A

recruits cohort of large antral follicles to enter a rapid growth phase

97
Q

What do the large antral follicles secrete?

A

low amounts of E2 and Inhibin B

98
Q

what does E2 and Inhibin B do?

A

negatively feed back on FSH

99
Q

What does a decline in FSH levels do?

A

cause atresia of all but 1 follicle

100
Q

What does the dominant follicle secrete?

A

high levels of E2

101
Q

What does high levels of E2 do?

A

positive feedback on gonadotropes resulting in a LH and (some) FSH surge

102
Q

What does the LH surge do?

A

induces meiotic maturation, ovulation, and luteinization

103
Q

What does the corpus luteum produce?

A

high progesterone, along with estrogen and inhibin A

104
Q

What does high progesterone, estrogen and inhibin A do?

A

negatively feedback on LH and FSH, returning them to basal levels

105
Q

What happens to the corpus luteum?

A

slowly becomes less sensitive to basal levels of LH, will die if not exposed to LH-like activity (i.e. hCG)

106
Q

What are the three layers of the uterus?

A

endometrium, myometrium, perimetrium

107
Q

What is the endometrium?

A

innermost, mucosal layer

108
Q

What is the myometrium?

A

thick muscular layer

109
Q

What is the perimetrium?

A

(serosal layer) - outer connective tissue and sersa

110
Q

is the cervix part of the endometrium?

A

no, it is distinct from the endometrium

111
Q

What is shed during menstruation?

A

endometrium - the functional zone

112
Q

What leads to the necrosis of the endometrial layer?

A

reduced blood flow to the spiral arteries (high resistance, low volume) leads to ischemia and necrosis of the endometrial layer

113
Q

What stimulates uterine cell growth

A

increased E2 during follicular phase

114
Q

What is dominant in the proliferative phase of the endometrial cycle?

A

estradiol

115
Q

What receptors are upregulated in response to E2 during the proliferative phase?

A

progesterone receptor

116
Q

What vascular changes occur during the proliferative phase?

A

increased vascularization

117
Q

What is dominant in the secretory phase of the endometrial cycle?

A

Progesterone

118
Q

What is a result of high progesterone in the secretory phase?

A

high progesterone from the corpus luteum has anti-estrogenic effects and stops further uterine growth

119
Q

What do the uterine cells secrete during the secretory phase?

A

large amounts of carbohydrate rich mucous

120
Q

What vascular changes occur during the secretory phase?

A

vascularization continues to increase

121
Q

What stromal changes occur during the secretory phase?

A

stromal cells undergo predecidualization and the stroma become edamatous

122
Q

What is the hormonal state of the menstrual phase of the endometrial cycle?

A

Low P4 and E2 due to demise of the corpus luteum

123
Q

What is a result of decreased blood flow to the spiral arteries?

A

ischemia and necrosis of the endometrium

124
Q

How else is the endometrium degraded?

A

proteolytic enzymes are increased

125
Q

does the released blood clot?

A

no - the necrotic tissue releases fibrolysins which prevents the blood from clotting

126
Q

What is the total volume loss in menstruation?

A

~30 mL

127
Q

What hormones dominate in the vagina during the mid- to late follicular phase?

A

estrogens

128
Q

What is the appearance of the vaginal cells in the follicular phase?

A

large, squamous, cornified with small or absent nuclei

129
Q

What hormones dominate in the vagina in the luteal phase

A

progesterone

130
Q

What is the appearance of the vaginal cells in the luteal phase?

A

small basophilic cells with many leukocytes

131
Q

What are the changes in cervical mucous during the follicular phase?

A

cervical mucous increases, becomes more alkaline and less viscous

132
Q

what are the changes in cervical mucous during the ovulatory phase?

A

characterized by spinbarkeit (stretchable mucous)and ferning (fern pattern when dried on a slide)

133
Q

What are the actions of estradiol (E2)?

A

inhibit growth of cohort follicles

alter cervical mucous to facilitate sperm transport

affect fallopian tube to favor transport of ovum and zygote

prepare endometrium for progesterone to evoke secretory response

prime GnRH action on LH secretion o evoke ovulatory surge of LH

134
Q

What is a primary releaser of E2?

A

the dominant follicle