Principles of Ovarian Follicular & Luteal Dynamics Flashcards

1
Q

What is the history of female reproduction?

A
  • in the 5th century BC, HIPPOCRATES suggested that generation of a new lifer was the action of 2 kinds of semen (male ejaculate & female menstrual blood)
  • a century later, ARISTOTLE characterized the ovary as an imperfect vestige of the male testis w/ no apparent function
  • in the mid-1600s, a Dutch physician, REGNIER DE GRAAF, recognized the ovary as an organ for egg production
  • all of these early modern scientists, however, held the mistaken belief that the follicle itself was the egg
  • in 1827, Estonian physician, KARL ERNST VON BAER, provided the 1st description of a mammalian egg from his microscopic study of ovarian vesicles (follicles) in the ovary of a dog
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2
Q

What is continuous follicular dynamics?

A

follicular growth & regression is a continuous pattern & is independent of the phase of the reproductive cycle

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3
Q

What is wave pattern follicular dynamics?

A

a reservoir of antral follicles remains in a resting stage, & at a particular time in each sp, 1 or several of these follicles begin to grow & reach maturity during the ensuing estrus

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4
Q

What are more than 95% of bovine estrus cycles composed of?

A

either 2 or 3 follicular waves

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5
Q

What 4 things do follicular dynamics consist of?

A
  1. recruitment
  2. selection
  3. dominance
  4. atresia
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6
Q

How do dominant follicles work in monotocous vs polytocous spp?

A

in monotocous sp (giving birth to a single offspring) ex: cow, mare, & woman, most reproductive physiologists consider that a single follicle is selected & will develop dominance. however, in polytocous spp (litter bearers), multiple dominant follicles are present

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7
Q

GnRH release & follicular dynamics

A
  • tonic & surge centers in the hypothalamus control GnRH release
  • the release of GnRH from the tonic center neurons occurs spontaneously in a rhythmic fashion
  • antral follicles of various sizes develop on response to tonic levels of FSH & LH & these antral follicles are always present
  • GnRH RELEASE FROM THE SURGE CENTER IS CONTROLLED BY HIGH ESTROGEN (which comes from growing antral follicles in the form of estradiol) ACCOMPANIED BY LOW PROGESTERONE. (it is essential to turn on the surge center to achieve ovulation)
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8
Q

The dynamics of follicles are synchronized by the interaction of which 4 hormones?

A
  1. FSH (follicle stimulating hormone)
  2. LH (luteinizing hormone)
  3. estradiol
  4. P4 (progesterone)
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9
Q

What is recruitment?

A
  • SMALL ANTRAL FOLLICLES ARE RECRUITED FROM THE OVARIAN POOL & PRODUCE SMALL AMTS OF E2
  • the phase of follicular development in which a cohort (group) of small antral follicles begins to grow
  • EMERGENCE OF A FOLLICULAR WAVE IS PRECEDED BY A SURGE IN PLASMA FSH CONCENTRATIONS (peak concentrations of FSH on the day before the follicular wave emergence)
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10
Q

What is selection?

A
  • follicles are selected from previously recruited small follicles & either become atretic or develop further
  • selected follicles produce moderate amounts of E2
  • follicles (not all) start shifting their dependence from FSH to LH, so they acquire LH responsiveness
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11
Q

What is dominance?

A
  • The dominant follicle of a wave is defined as the one that reaches the largest diameter
  • SELECTED FOLLICLES THAT DO NOT BECOME ATRETIC BECOME DOMINANT FOLLICLES THAT PRODUCE LARGE QUANTITIES OF E2
  • DOMINANT FOLLICLES WILL OVULATE
  • IN POLYTOCOUS SPP, MORE THAN ONE FOLLICLE IS SELECTED. HOWEVER IN MONOTOCOUS SPP ONLY A SINGLE FOLLICLE IS SELECTED.
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12
Q

What is atresia?

A

degeneration of antral follicles

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13
Q

How does the dominant follicle become dominant?

A
  • FSH starts the follicular wave
  • IN THE FACE OF THE POSTSURGE DECLINE IN FSH, THE GROWTH OF MOST OF THE FOLLICLES IN OF A WAVE STOPS, & THEY BEGIN TO REGRESS w/in 2 to 5 days of emergence
  • the transient rise in FSH permits sufficient follicular growth so that some (not all) follicles acquire LH responsiveness
  • the ability of the dominant follicle to transition from FSH to LH is critical for the selection of a single dominant follicle in cattle
  • THE DOMINANT FOLLICLE MAINTAINS ITS GROWTH BY TRANSITIONING ITS DEPENDENCE FROM FSH TO LH
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14
Q

How are dominant follicles ovulated?

A
  • dominant follicle produces increasing amts of estradiol (estrogen), which causes positive feedback to the anterior pituitary
  • ONCE ESTROGEN LEVELS REACH A THRESHOLD LEVEL, A SURGE OF LH (at least 10x greater than tonic levels) results in ovulation
  • peak estradiol concentration in the follicular fluid of the ovulatory follicle is twice as high as the peak in anovulatory dominant follicles
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15
Q

What happens when estradiol crosses its threshold?

A
  • it turns its negative feedback on GnRH secretion to positive feedback; resulting in LH surge for ovulation
    Follicular phase:
  • hypothalamus -> releases GnRH -> acts on anterior pituitary -> releases FSH & LH -> act on follicles in ovaries (PITUITARY HORMONE EFFECT: LH & FSH stimulate several follicles to grow) -> Estradiol negative feedback on hypothalamus (OVARIAN HORMONE EFFECTS: follicles produce low levels of estradiol that inhibit GnRH secretion by the hypothalamus, keeping LH & FSH levels low)
    Ovulation:
  • hypothalamus -> releases GnRH -> acts on the anterior pituitary -> releases FSH & LH -> act on follicles in ovaries (PITUITARY HORMONE EFFECT: LH & FSH stimulate maturation of 1 of the growing follicles) -> estradiol positive feedback on hypothalamus (OVARIAN HORMONE EFFECTS: growing follicles begin to produce high levels of estradiol which stimulate GnRH secretion by the hypothalamus. LH & FSH levels rise, resulting in ovulation about a day later
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16
Q

How does the corpus luteum develop after ovulation and how is it related to progesterone production?

A
  • @ the time of ovulation, antral contents are evacuated, & the wall of the ovulatory follicle collapses into undulations w/in the vacated antrum, which is known as corpus luteum (CL)
  • CL produces progesterone
  • plasma progesterone concentration is highly correlated w/ CL weight & volume
  • ex: plasma progesterone concentration is ~<2 ng/ml three days after ovulation, ~4 ng/ml by six days, & peak concentrations >6 ng/ml btwn 10 & 14 days postovulation. due to luteolysis, levels decrease after 16 days.
17
Q

Luteal phase pathway:

A

hypothalamus -> releases GnRH -> acts on the anterior pituitary -> release FSH & LH -> act on the corpus luteum in the ovaries (PITUITARY HORMONE EFFECT: LH stimulates growth of a corpus luteum from follicular tissue left behind after ovulation) -> progesterone has negative feedback on anterior pituitary & hypothalamus (OVARIAN HORMONE EFFECT: the corpus luteum secretes progesterone that blocks GnRH production by the hypothalamus & LH & FSH production by the pituitary

18
Q

How does high progesterone from the CL prevent ovulation?

A

tonic center of hypothalamus -> releases GnRH -> FSH released from anterior pituitary -> growing follicles produce estradiol -> effect of estradiol on surge center is blunted due to high levels of progesterone -> no LH surge -> no ovulation

19
Q

How does ovulation occur when there is low progesterone from the CL?

A

tonic center of hypothalamus -> releases GnRH -> FSH released from anterior pituitary -> growing follicles produce estradiol -> estradiol (above threshold) activates the surge center of the hypothalamus -> LH surge -> ovulation

20
Q

How does endogenous (or exogenous) progesterone (from CL) work?

A
  1. regular emergence of anovulatory follicular waves (waves still occur in pregnant animal but they are anovulatory waves due to high progesterone)
  2. dose related suppression of LH & dominant follicle growth
  3. maximum follicle diameter & intra-wave-interval (IWI) decrease (b/c follicle is dying early so next wave starts earlier)
    - follicular waves occur throughout gestation except last 21 (days?)
21
Q

What is luteolysis?

A
  • IF PREGNANCY DOES NOT OCCUR SUCCESSFULLY, RAPID LUTEOLYSIS IS CAUSED BY PROSTAGLANDIN F2alpha (PGF2a), WHICH IS RELEASED FROM THE ENDOMETRIUM around days 17-19 of the cow’s estrous cycle.
  • a precipitous drop in progesterone production is caused by luteal cell death from disruption of the vascular supply, the release of cytokines, & infiltration of macrophages
22
Q

How does PGF2a work in our different common domestic spp?

A
  1. via systemic route (in mares)
  2. via local route (in Ru)
  3. both local & systemic (Sw & camelids)
  4. dogs
    - progesterone profile similar in pregnant & nonpregnant dogs (~60 d post-LH surge is same in both)
    - in pseudopregnancy, progesterone drops slowly; in pregnant, it drops suddenly
23
Q

How does the regular emergence of anovulatory follicular waves occur in prepubertal calves?

A
  1. FSH surges coupled to wave emergence
  2. follicle dominance increases w/ age
  3. max follicular diameter & IWI increases w/ age (follicle takes longer to die)
  4. circulating [LH] increase w/ age
24
Q

Describe the first ovulatory cycle in calves:

A

it is short
- 8 days
- short-lived, under-developed CL
- 1 follicular wave

25
Q

What does FSH start?

A

the follicular wave

26
Q

If progesterone production is high, what happens to LH? ovulation? the follicles?

A
  • there will be no LH peak (NO OVULATION)
  • the follicles will die
27
Q

If progesterone is low, what happens with estradiol?

A
  • estradiol (produced by the dominant follicles) causes positive feedback to the anterior pituitary for an LH surge
28
Q

What does the LH surge do?

A

it releases oocytes from the dominant follicles (OVULATION)

29
Q

What do ovulation kits detect?

A

LH b/c if there is LH then ovulation has happened

30
Q

95% of cycles are which patterns?

A

2 or 3 wave patterns

31
Q

Differences btwn 2 & 3 wave patterns?

A
  1. duration of cycle (19-20 vs 22-23 days)
  2. interwave interval (10 vs 8 days)
  3. maximum size of 2nd dominant follicle (15 vs 13 mm)
  4. onset of luteolysis (day 18 vs 16)
32
Q

Did pregnancy rates differ btwn 2 & 3 wave cycles?

A

no, in some studies

33
Q

What are the predictive characteristics & repeatability of wave patterns in 2 vs 3 wave cycles?

A
  • If < or = 21 days, 2 wave intra ovulation interval (IOI)
  • if > or = 22 days, 3 wave IOI
34
Q

What is the strongest correlate of two wave vs three wave patterns?

A

duration of dominance of Wave 1

35
Q

What is the old concept of the initiation of follicular dominance?

A
  • the follicular wave emergence in cattle is characterized by the sudden (w/in 2-3 days) growth of 8-41 small follicles that are initially detected by U/s at a diameter of 3-4 mm
36
Q

What is the current concept of the initiation of follicular dominance?

A
  • wave emergence @ 1 mm (2.5 days earlier than previously known)
  • exquisite FSH sensitivity (w/in 6 hr)
  • dominance (size advantage from time of emergence)
  • hierarchical progression over the entire FSH surge (the dominant follicle (DF) emerged 6-12 hrs earlier than the 1st subordinate follicle)
37
Q

What is reproductive senescence?

A
  • refers to the gradual decline in reproductive capacity w/ age
38
Q

What occurs w/ aging?

A
  • continued 2 or 3 wave patterns
  • most mother-daughter pairs had the same pattern
  • elevated FSH
  • interovulatory & interwave intervals did not change
  • CL smaller & progesterone lower
  • fewer follicles @ wave emergence
  • lower super stimulatory response
  • lower fertilization rate