Reproduction 4: Female Repro (Continued) Flashcards Preview

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Flashcards in Reproduction 4: Female Repro (Continued) Deck (79):
1

what is primary amenorrhea?

absence of menses in a phenotypic female by age 17

2

What are some common causes of primary amenorrhea?

disorders of sexual differentiation

3

What are some disorders of sexual differentiation that can result in primary amenorrhea?

Turner's Syndrome: no ovaries

Complete androgen resistance (testicular feminization): no ovaries

Hormonal disorders in ovaries, adrenals, thyroid, pituitary/adrenal/hypothalamic axis

4

What is secondary amenorrhea?

cessation of menstruation for longer than 6 months

5

What are the main causes of secondary amenorrhea?

pregnancy, lactation, menopause

6

What are some less common causes of secondary amenorrhea?

prolactinoma
panhypopituitarism

7

What is the problem with a prolactinoma?

excess prolactin inhibits GnRH

8

What is oligomenorrhea?

infrequent periods (cycle length >35 days)

9

What is the most common cause of oligomenorrhea?

Changes due to functional abnormalities in CNS mechanisms that regulate GnRH release, including stress and illness

10

What are some other causes of oligomenorrhea?

changes in body fat composition (very low levels)

Intense exercise, extreme weight loss, anorexia nervosa – no consistent changes in plasma gonadotropins or ovarian steroids

11

What is dysmenorrhea?

painful menses

12

What are some causes of dysmenorrhea?

prostaglandin released during menses can cause uterine contractions which may be severe enough to cause ischemia and pain

13

What is a social result of dysmenorrhea?

single most common cause of female work/school absenteeism

14

What is prostaglandin synthesis promoted by?

E2, followed by progesterone

15

How do you treat dysmenorrhea?

prostaglandin synthesis inhibitors, oral contraceptions

16

What is premenstrual syndrome and premenstrual dysphoric disorder?

physical and behavioral symptoms that interfere with normal life, 30% women with normal cycles

17

What are the symptoms of PMS?

abdominal bloating, extreme sense of fatigue, breast tenderness, labile mood, irritability, depression, tension

18

What is a treatment of PMS and what has been shown not to work?

linked to cycle, but no clear link to progesterone - progesterone replacement therapy doesn't work

vitamin supplement also doesn't work

SSRI first line treatment if socioeconomic dysfunction present

19

What is hirsutism?

inappropriate hair growth in androgen sensitive areas (beard area, back, etc.)

20

What are some causes of hirsutism?

excessive androgen intake

excessive androgen production by adrenals (adrenal hyperplasia, cushing's)

idiopathic increases in sensitivity to androgens

21

What is virilization?

includes hirsutism and more pronounced evidenc eof androgen stimulation, such as deepening voice, clitoral hypertrophy, temporal balding, male pattern skeletal development

22

What is the cause of virilization?

excessive androgen production

23

What is polycystic ovarian syndrome (PCOS)?

accumulation of preantral follicles that become cysts

24

What is a root cause of PCOS?

insulin resistance and obesity --> causes of and caused by PCOS

High insulin stimulates androgen production (causing infertility) and increased conversion to estrogens (weight gain)

25

What is a consequence of PCOS on the ovaries?

follicle development impaired, ovulation is not complete, and the follicles degenerate into cysts. ovaries can double (or more) in size

26

What is PCOS a leading cause of?

infertility

27

What are some symptoms of PCOS?

sleep apnea (consistent with obesity), oligomenorrhea, obesity, acne, decreased HDL and increased triglycerides, hirsutism

28

What is the treatment for PCOS?

weight loss, smoking cessation, Metformin

Metformin alone is often sufficient to restore fertility

Clomiphene also effective

29

What are the three types of estrogen?

E1 - estrone

E2 - 17-beta-estradiol

E3 - estriol

30

What are the general features of estrone (E1)?

produced in higher amounts after menopause, lower affinity for estrogen receptor

31

What are the general features of estradiol (E2)?

primary circulating hormone during reproductive years, higher binding affinity for estrogen receptors

32

What are the general features of estriol (E3)?

produced by the placenta - only high during pregnancy

also converted from estrone in the liver

weak binding to estrogen receptors

33

How are estrogens transported in the blood?

38% bound to SHBG

60% bound to albumin

1-2% free

34

How are estrogens processed by the target tissues?

high conversion in target tissues by aromatase - high local concentrations

35

What are some diseases associated with a loss of estrogen (menopause)?

alzheimers, stroke, cardiovascular disease, osteoporosis, ovarian cancer, breast cancer, uterine cancer

36

What kind of receptor are estrogen receptors (ERs)?

nuclear steroid hormone receptors

37

What are the two kinds of estrogen receptors, and what are their general features?

ER-alpha: mediate most reproductive effects of estrogen (knock out mice are infertile)

ER-beta: mediates non-reproductive effects (mood, cardioprotection, neuroprotection). ER-beta knock out mice are subfertile

38

Which ER does E2 bind?

both, with equal affinity

39

Which receptor has a higher affinity for plant-derived estrogens (e.g. from soy)?

ER-beta

40

What are selective estrogen receptor modulators (SERMs)?

synthetic compounds specifically designed to target ERs

41

What do SERMs do?

can bind both ERalpha and ER beta and have tissue specific actions

ex: tamoxifen, clomiphene

42

What does tamoxifen do?

Tamoxifen is an antagonist in the breast and uterus, but an agonist in bone and the brain

43

What does clomiphene do?

originally designed to treat oligomenorrhea

selective for ER alpha, very low binding to ER beta

antagonist for ERalpha, specific for hypothalamus (blocks negative feedback)

induces ovulation

44

What are the progesterone receptors, and what increases their expression?

PR A and B

nuclear steroid hormone receptor family

E2 upregulates

45

How is progesterone (P4) transported?

mostly bound to albumin, very low affinity for SHBG

46

What are the actions of progesterone?

prepares endometrium for implantation of embryo (proliferation, synthesis of enzymes that lyse zona pellucida)

inhibits myometrium contractions (maintains pregnancy)

stimulates mammary gland development (preparation for lactation)

antagonizes actions of estrogen (important consideration in hormone replacement therapy)

47

What are the hormonal changes in menopause?

depletion of ovarian follicles results in decreased E2 and P4 production, and decreased inhibins

the loss of negative feedback increases FSH and LH (FSH>LH)

48

What are women in menopause at increased risk for, and why?

osteoporosis: E2 stimules OPG (protective for bone)

Cardiovascular disease: E2 protects against cardiac hypertrophy and reduces cholesterol

Vascular flushing (hot flashes): increased gonadotropins results in increased core body temp, reflex vasodilation

dementia: E2 is neuroprotective

vaginal atrophy and dryness: decreased E2induced cellular proliferation and decreased secretion of cervical mucous

49

What quadruples between ages 20 and 40?

infertility

50

What increases with maternal age?

pregnancy complications

51

What is the site of fertilization, and how many sperm reach this area?

ampulla of oviduct, 50-100 million sperm out of 150-600 million deposited in the vagina reach this area

52

what helps the sperm reach the ampulla of the oviduct?

vaginal secretions become more alkaline and less viscous

uterine and cervical contractions propel sperm forward

prostaglandin in seminal plasma induces muscle contractility

vaginal secretions prevent semen from coagulating and forming a plug

53

What is the first step in the fertilization process?

gamete transport

54

How does the oocyte reach the ampulla?

only one oocyte released from ovary into the peritoneal cavity, cumulus cells help the fimbriae capture the oocyte and direct it towards the oviduct

55

Where do the first stages of embryonic development occur?

stays about 3 days in the ampulla of oviduct where the start of blastocyst formation occurs - the first few cell divisions

56

What does the egg enter the uterine cavity as?

a morula (days 3-4)

57

What is the second step of fertilization?

sperm penetration of oocyte

58

What is the final step in sperm maturation?

capacitation

59

What is capacitation?

allows sperm to penetrate the zona pellucida surrounding oocyte

involves removal of protective protein coat

60

Name and describe the mechanism that allows sperm to breach the zona pellucida

the acrosomal reaction: the sperm binds to ZP3 (glycoprotein) receptors which stimulates increased calcium in the sperm resulting in a release of hydrolytic enzymes

these sperm can then bind ZP2 receptors and the sperm and oocyte membranes can fuse

61

What prevents multiple sperm from entering an oocyte?

the cortical reaction

62

describe the cortical reaction

Ca mediated release of cortical granules, these enzymes will prevent ZP3 and ZP2 binding and lead to "hardening" of zona pellucida

Ca release also leads to meiosis II and extrusion of polar body

63

What does the cortical reaction prevent?

polyspermy - triploid cells not viable

64

What is "hatching" of the embryo during implantation?

dissolution of the zona pellucida by trophoblast cells

65

discuss the differentiation of the blastocyst at implantation

trophoblast differentiates into cytotrophoblast and syncytiotrophoblast

66

What does the cytotrophoblast do?

initially the feeder for continually dividing cells

67

What does the syncytiotrophoblast do?

adhesion, invasion, endocrine

68

What do embryos express that facilitates adhesion?

syncytiotrophoblasts secrete adhesive surface proteins (integrins and cadherins)

69

What is the bridging molecules between the embryo and endometrium?

Osteopontin: E2-dependent secreted by uterine glands

70

How do stromal cells facilitate adhesion?

Stromal cells form decidua and secrete nutrients. Will later become a barrier and endocrine organ

71

What is the physical result of embryo invasion?

embryo completely burrows into superficial layers of the endometrium (most invasive of all mammals)

72

What prevents the trophoblast from penetrating the endometrium to deeply?

balance between decidual cells (defense - inhibitors of MMP, IGF-BP) and trophoblast migration (offense - MMP and IGF2 secretion)

73

What are lacunae?

fluid filled spaces in the syncytium that make contact with the maternal blood vessels

74

What forms the chorionic villus?

cytotrophoblasts proliferate and invade the syncytiotrophoblast

75

describe a mature villus

fetal tissue protruding into maternal blood - the brush border of the syncytiotrophoblast faces maternal blood

76

Vascular remodeling is essential or fetal life. describe these vascular changes

conversion of high resistance, low capacity to low resistance, high volume vessels

Spiral arteries increase in diameter as the muscular and elastic properties are lost

77

What is preeclampsia-eclampsia?

relative placental ischemia leads to oxidative stress and endothelial damage. The damaged epithelial cells will increase vasoconstrictors and decrease vasodilators, which will worsen placental hypoperfusion.

Breach of endothelial cell barrier between platelets and basement membrane leads to capillary leak resulting in edema and proteinuria

78

What is the leading cause of maternal death in developed countries?

preeclampsia-eclampsia

79

What are the hallmark symptoms of preeclampsia-eclampsia?

hypertension
proteinuria
edema