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Reproductive and Developmental Biology > Lecture 5 - Female Reproductive Systems > Flashcards

Lecture 5 - Female Reproductive Systems Flashcards

1
Q

Ovipositor - invertebrates

A

something to position eggs

can be simple tubes or something more complex, tend to be associated with invertebrates but some vertebrates have them

dragonfly

  • lay eggs and glue to substrate (eg underside of reed)

grasshopper

  • dig into ground and deposit eggs underground
  • no glue produced
  • back end of abdomen is used to bury

hymenoptera

  • ants and wasps have specialized ovipositors that can double as a sting
  • usd as parasitoid wasps to inject eggs into eg a tarantula
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2
Q

Ovipositor - teleosts

A

Japanese bitterling

  • innoculates a muscle with her eggs using an ovipositor
  • she injects her eggs into the gill favity of the swan mussel
  • her eggs are safe inside the gill filaments of the mussel
  • next challenge is for male to fertilize the eggs
  • ejaculates into the inlet of the mussel where there’s a natural flow so the sperm flows over the eggs
  • the mussel is parasitized and the fish eat it from the inside out as they grow

sygnathidae (sea horses)

  • inserts ovipositor into his prood pouch
  • sex role reversal
  • male retains the sperm she ejects the eggs
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3
Q

Female reproductive anatomy (human)

(picture)

A
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4
Q

Female reproductive anatomy (human)

A
  • simple uterus
  • fundus is body of the uterus
  • oviduct - leading away from the uterus - egg tube with 2 parts
    • sperm comes up through the uterus and becomes decapacitated when it passes through the isthmus
    • fertilization takes place in the ampulla and the embryo rolls down into the uterus
  • 2 different layers of the uterus
    • endometrium - inner glandular layer
    • myometrium - outer muscular layer
  • os has 2 parts
    • external os - where primates deposit semen
    • internal os - where boars deposit semen
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5
Q

Female reproductive anatomy (human) - more detailed

A
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6
Q

Fundus

A

body of the uterus

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7
Q

Oviduct

A

egg tube leading away from the uterus

2 parts - isthmus and ampulla

  • sperm comes up through the uterus and becomes decapacitated in the isthmus
  • fertilization takes place in the ampulla

then embryo rolls down into the uterus

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8
Q

Corpus of the uterus

A

cavity

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9
Q

Layers of the uterus

A
  • endometrium - inner glandular layer
  • myometrium - outer muscular layer
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10
Q

Os parts

A
  • external os - where primates deposit semen
  • internal os - where boars deposit semen (corkscrew penis)
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11
Q

Uterine histoloty - eutheria

A

4 basic designs

  • duplex uterus
  • bipartite uterus
  • bicornate uterus
  • simplex uterus
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12
Q

Duplex uterus

A

2 seperate uteri + 2 separate cervixes

  • most primitive
  • seen in rodentia and lagomorpha
    • why rodents are so prolific - can be pregnant in both cervixes
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13
Q

Bipartite uterus

A
  • 2 uteri + 1 certix
  • carnivora and cetacea
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14
Q

Bicornate uterus

A
  • 2 uterine horns + 1 cervix
  • insectivores and ungulates
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15
Q

Simplex uterus

A
  • 1 uters + 1 cervix
  • less prolific/very few offspring
  • primates, chrioptera, edentates
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16
Q

Uterine histology - Eutheria

picture

A
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17
Q

Ovarian glands - picture

A
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18
Q

Ovarian glands

A
  • oocytes = primordial follicle
  • secondary follicle produces estradiol as the major ovarian sescretion in the first half of the cycle
  • the oocyte and the surrounding somatic cells cooperate to produce estradiol
  • the cells which make up the follicel are destined to become the corpus luteum in the second half of the cycle - which produces progesterone
    • pro = for, gest = gestation
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19
Q

The ovarian cycle - part 1

A
  • primordial follicle = oocyte and single layer of granulosa cells
  • as it becomes a pre-antral follicle the oocyte is much bigger
  • then have multiple layers of granulosa cells, start getting theca cells around the edge
  • theca cells differentiate to
    • theca interna (base membrane)
    • theca externa
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20
Q

The ovarian cycle - part 1

primordial follicle

A

oocyte + granulosa cells

  • oocytes start out as primordial germ cells in the yolk sac and invade the embryo (don’t start in gonads)
  • if teh germ cells find themselves in ovaries = oogonia, in testes = spermatogonia
  • oogonia enter meiosis, become oocytes, committed to meiosis
  • granluosa cells look after the eggs
    • somatic cells, like sertoli cells in males
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21
Q

The ovarian cycle - part 1

pre-antral follicle

A

oocyte + granulosa + theca cells

  • the primordial follicle becomes pre-antral follicle
  • granluosa cell layers divide
  • new cell type appears and surrounds the granulosa cells = theca cells
  • theca cells surrounding granulosa cells
    • like leydic cells around sertoli cells
    • leydig cells produce testosterone (androgen) in response to LH
    • theca cells produce androgens in response to LH
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22
Q

The ovarian cycle - part 1

antral follicle

A
  • has cavities - somatic cells divide by mitosis (exponentially)
  • however the follicle is a sphere so 4/3 Πr3
  • follicle grows more quickly than cells grow to fill it
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23
Q

The ovarian cycle - part 1

pre-ovulatory follicle

A
  • as this structure gets bigger, granulosa cells called mural granulosa cells (wall of follicle)
  • cumulus granulosa cells (form cloud around oocyte)
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24
Q

The ovarian cycle - part 1

follicles

A
  • primordial follicle
  • pre-antral follicle
  • antral follicle
  • pre-ovulatory follicle
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25
Q

Functions of estradiol

A
  • exerts negative feedback within HPG axis
  • acts on endometiral cells as a mitogen - stimulates proliferation of endometrium ready for embryo implantation
  • causes breast cells to divide
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26
Q

Follicular estradiol biosynthesis

A

cholesterol

→

progesterone

→

androgen

→ (requires enzyme CYP19A1 aromatase)

estrogen

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27
Q

Follicular estradiol biosynthesis

Androstenedone

A

→

estrone (E1)

(1 hydroxyl)

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28
Q

Follicular estradiol biosynthesis

Testosterone

A

→

estradiol (E2)

(2 hydroxyl groups)

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29
Q

Follicular estradiol biosynthesis

16-OH-testosterone

A

→

estriol (E3)

(3 hydroxyls)

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30
Q

Two cell - two gonadotrophin

model of follicular steroidogenesis

A

ovarian follicle has 2 major somatic cell types

  • theca cells
  • granulosa cells

separated by a strong basal membrane

  • theca cells make androgen
  • granulosa cell has no blood supply because of thick basal membrane which can’t be penetrated by blood vessels

→ no way to get blood supply to it (granulosa cells = avascular)

  • cholesterol can’t get to granulosa cells - has to rely on androgen to make steroids
    • converts androgen to estrone
    • (steroids can fuse through membrane)
  • theca cells respond to LH (like Leydig cells)
  • granulosa cells respond to FSH (like Sertoli cells)
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31
Q

Two cell - two gonadotrophin

model of follicular stroidogenesis

picture

A
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32
Q

The HPO axis in the follicular phase of the ovarian cycle

picture

A
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33
Q

The HPO axis in the follicular phase of the ovarian cycle

A
  • GnRH from the hypothalamus to the anterior pituitary wher it will stimulate the production of gonadotrophins (LH and FSH)
  • need both LH and FSH if going to make estradiol
  • estradiol is linked to long-loop negative feedback to suppress GnRH
    • whereas short-loop negative feedback suppresses LH and FHS
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34
Q

The ovarian cycle - part 2

ovulation

A
  • how an egg develops surrounded by somatic cells as it goes through primordial, pre-antran, and pre-ovulatory folllicles
  • the cells which are left behind form the corpus luteum
    • made up of luteinized granulosa cells and theca cells
  • when the corpus luteum dies it loses its yellow color and becomes a white body - the corpus albicans
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35
Q

The ovarian cycle - part 2

A

ovulation

  • release of cumulus-oocyte complex

corpus luteum (“yellow body”)

  • luteinized granulosa and theca cells

corpus albicans

36
Q

Luteinization

A
  • the change of granulosa and theca cells into granulosa luteal or theca luteal cells requires them to become mixed and vascularized
  • the cells become enormous, corpus luteum have
    • large luteal cells form granulosa cells (GL)
    • smallluteal cells from theca cells (TL)
  • driven by LH
  • hypertrophy, different pigment
  • mixing of vascularized granulosa- and theca-derived luteal cells
  • cellular hypertrophy
    • “large” luteal cells (GL)
    • “small” luteal cells (TL)
  • accumulation of lutein
    • antioxidant, carotenoid pigment
  • major product is progesterone
37
Q

Functions of progesterone

A
  • exerts negative feedback within HPG axis (on ovarian cycle)
  • thickens cervical mucus
    • blocks passage of sperm across cervical os
  • switches off estrogen receptor so uterine(?) can no longer proliferate
  • exerts anti-proliferative effect on endometrium (dec. ER expression)
  • stimulates differentiation of endometrial cells - decidualization
  • stimulates secretion of uterine nutrients from endometrial glands
  • increases bloodflow to uterus
  • estradiol about making the endometrium thick - progesterone about making the endometrium functional
38
Q

Two cell - one gonadotrophin model of luteal steroidogenesis

A
  • the 2 cells-2 gonadotrophin model of follicular steroidogenesis separated by basal membrane
  • when these cells are luteinized they’re all exposed to blood and all get cholesterol

→ theca-derived luteal cells will be able to make progesterone and secrete, and so will granulosa-derived theca cells → estradiol in primates

  • all of this is under the control of LH
  • THE CORPUS LUTEUM ONLY NEEDS LH
39
Q

Two cell - one gonadotrophin model of luteal steroidogenesis

picture

40
Q

HPO axis in the luteal phase

picture

41
Q

HPO axis in the luteal phase

A
  • if we switch to ovulation have corpus luteum in the ovary
  • if primate - will reduce progesterone
  • long- ad short-loop negative feedback to suppress LH
    when the corpus luteum is no longer needed it will undergo luteal regression
42
Q

Luteal regression/luteolysis

A

2 step process

functional luteolysis

  • corpus luteum stops making progesterone (dec. P4)

structural luteolysis

  • cells burst, corpus luteum → albincans then bursts
  • the corpus luteum will stop making progesterone about a month before it bursts
    • could reflec the decline in LH support
      • corpus luteum runs on LH
      • loss of LH could cause it to die
    • could reflect antigonadotrophic actions of PGF2α (ovarian or uterine)
      • in other species there is an active hormone that cuases the function of corpus luteum to stop working - PGF2α
      • the quickest way to transport something is counter current exchange in the ovary
      • hormones made in the uterus leaving the uterine (?) vein go straight into the uterine (?) artery
      • in priates we can take the uterus out and it doesn’t affect the corpus luteum
        • the prostaglandins may be made in the ovary itself
43
Q

The ovarian cycle has 2 phases

A
  • ovicular phase - dominated by ovarian follicles
  • luteal phase - dominated by the corpus luteum
44
Q

The ovarian cycles are distinct from either

A
  • oestrous cycles
  • menstrual cycles
45
Q

The menstrual cycle is really rare

A

only really seen in higher primates like humans,

possibly in elephants,

only in some bats

46
Q

The Menstrual (Uterine) Cycle

A
  • all about the endometrium
  • as higher primates we lose the surface layers of the endometrium at menses
  • can’t have menstrual cycle if there isn’t menses/loss of blood
  • the endometrium breaks down, gets thinner, then proliferates again
    • in humans if a 28 day cycle the endometrium proliferates over the first 14 days
47
Q

The menstrual cycle has 2 phases

A
  • proliferative phase
    • endometrium proliferates
    • estradiol
  • secretory phase
    • endometrium secretes
    • secretes nutrients for the early embryo
    • progesterone
  • making something for the blastocyst to attach to and implant
48
Q

The Menstrual (Uterine) cycle

(picture)

49
Q

The phases of the menstrual/endometrial cycle corresponde with

A

the phase of the ovarian cycle

but they are 2 separate cycles

50
Q

The proliferation of the endoemtrium is driven by

A

estradiol - a mitogen

  • in us this is identical to the follicular phase of the ovarian cycle
  • the words are not interchangeable
51
Q

The secretory phase is driven by

A

progesterone from the corpus luteum

  • secretory phase of the endometrial cycle corresponds with the luteal phase of the ovarian cycle
52
Q

In us - because we menstruate we…

A

take out timing for menses

  • when we talk about day 1 we talk about te first day of menstruation
53
Q

Menstrual and Ovarian Cycles

(picture)

54
Q

The menstrual cycle depends on

A

the ovarain cycle

55
Q

In the follicular phase of the ovarian cycle we starte wtih some

A
  • follicle stimulating hormones (FSH)
  • wake up those follicles that have been sleeping for maybe 40 years
  • this stimulates the production of estradiol which increases as the follicles grow
  • the the follicle goes from primordial to pre-antral to antral to ovulatory it produces more and more estrogen which stimulates the endometrium to proliferate
  • around mid-gestation get a surge in LH
  • the follicle ruptures, the remnants become a corpus luteum which makes progesterone which causes the endometrium to secrete
  • this is not coincidental - the steroids coming from the ovary are driving the endometrium
56
Q

What if an animal doesn’t menstruate?

A

if dealing with any other mammals, especially non-primates, talk about the oestrous cycle

57
Q

Oestrous

A

period of sexual receptivity

  • when a female is in heat
58
Q

When should oestrous occur?

A

at the time of ovulation

  • only makes sense to do when fertile
  • the day of oestrous will be the day of ovulation
59
Q

Day 1 of the oestrous cycle is

A
  • the start of ovulation
  • means that start the cycle with the corpus luteum and progesterone
  • start with luteal phase and go to the follicular phase of the next ovarian cycle
60
Q

Oestrous cycle

(picture)

61
Q

Menstrual v Oestrous Cycle

A
  • menstrual cycle - day 1 coincides with the start of the follicular phase
  • oestrous cycle - reference point starts at luteal phase of one cycle then the follicular phase of the next, and then the next ovulation
62
Q

Folliculogenesis

A
  • primordial follicle = oocyte + single layer of granulosa cells
  • preantral follicle = oocyte + multiple layers of granulosa cells
  • antral follicle = multiple layers of Gc and theca cells + antrum
  • ovulatory follicle = multiple layers of GC and TC + single large antrum
  • the sphere gets bigger faster than doubling so get small gaps opening betwen the granulosa cells which will coalesce to form a single antrum
63
Q

Folliculogenesis

(steps)

A
  • primordial follicle
  • pre-antral follicle
  • antral follicle
  • ovulatory follicle
64
Q

Folliculogenesis

(picture)

65
Q

The development of the pirmordial and pre-antral follicles doesn’t require

A

hormones

  • but if there are they’re local hormones
  • not LH or FSH
  • don’t need FSH for early stages of folliculogenesis
  • it’s only early antral follicles which respond to FSH
  • when that gap starts to appear between the granulosa cells that the cells become responsive to FSH
  • that regulate FSH receptors
66
Q

When the gap starts to appear between the granulosa cells

A

the cells become responsive to FSH

67
Q

When a follicle matures it

A

becomes responsive to LH as well

68
Q

The theca cells were always LH-responsive, but in the late antral stages …

A

the granulosa cells (around ovulation) become responsive to LH as well

69
Q

LH and FSH in folliculogenesis

A
  • the development of primordial and pre-antral follicles does not require hormones
  • early antral follicles respond to FSH
  • when the gap starts to appear betewen the granulosa cells they become responsive to FSH
  • when a follicle matures it becomes responsive to LH as well
  • theca cells were always responsive to LH bu tin te late atnral stages the granulosa cells become responsive to LH as well
  • an ovulatory follicle respodns to LH everywhere
  • early antral follicles - FSH only
  • late antral follicle s- FSH in the granulosa, LH in the theca
  • ovulatory follicles - every cell is responding to LH because LH receptors have been switched on in the granulosa cells
70
Q

Endocrine support of follicle development and function

A
  • primordial and pre-antral follicles
    • gonadotrophin-independent
  • early antral follicles
    • respond to FSH
  • ​late antral follicles
    • respond to FSH (granulosa) and LH (theca)
  • ovulatory follicles
    • respond to LH
71
Q

Follicular atresia

(picture)

A

(first cells = preantral follicles)

(antresia = apoptosis via caspases etc)

(final cell = monotocus - only 1 antral goes through)

72
Q

Most follicles die

A

follicular atresia

(eg picture - of this pool in a given month of pre-antral follicles, only 6 made it through and rest lost by a process of atresia)

(of those pre-antral follciles we’re monotocus - only 1 makes it through)

the only one that doesn’t undergo atresia is the one that responds well to FSH and LH

73
Q

Atresia

A
  • a process of apoptosis
  • expression of caspases and other mitochondrial genes associated with apoptosis
74
Q

Follicle selection/Dominance

A
  • the follicle that makes it through is the one that responds well to LH
  • the others die of atresia
  • dominant follicle in monotocus
  • produces most estradiol → greatest negative feedback, suppress FSH and LH to kill ones that aren’t very sensitivte → still responds to jsut LH
75
Q

Follicle selection/Dominance

(picture)

76
Q

Changing responsiveness to gonadotrophins in the dominant follicle

A
  • the most FSH-responsive follcile makes the most E2
  • negative feedback from E2 suppresses FSH
  • E2 upregulates LHCGR (LH receptor) on GCs
  • only one follicle which responds to LH and FSH the best will go through to ovulation
  • still have follicular dominance in a polytocus specis because not all of them make it through
  • the dominant/selected follicles are the ones that produce the most estradiol
  • produce most estradiol, therefore have the greatest exertion of negative feedback on the pituitary gland
  • the largest follicles - the dominant follicles - will suppress FH and LH
  • that will kill all of the follicles that aren’t very sensitive
  • only the most sensitive one will continue to respond to those declining levels of FSH
  • that follicle which is responsive to FSH cuts off the FSH supply to everything else
  • it’s the one that becomes responsive to just LH
  • producing estradiol, suppressing FSH, running on LH
77
Q

Follicular dominace

summary

A
  • the most FSH-responsive follicle is the one which makes the most estradiol
  • estradiol suppresses FSH but crucially upregulates LH receptor (LHGCR) on the granulosa cells
  • the follicle that switches to not needing FSH and denyint it to every other follicle in the cell
78
Q

Ovulation occurs mid-cycle between

A

the follicular phase and the luteal phase

79
Q

Ovulation occurs mid-cycle between the follicular phase and the luteal phase

80
Q

Ovulation occurs mid-cycle between the follicular phase and the luteal phase

A
  • end of the follicular phase
  • start of the luteal phase
81
Q

Text books are wrong

A
  • say you go from primordial trough to ovulatory follicle in the 2 weeks of the follicular phase
  • will you tell that the corpus lutuem dies within 2 weeks
  • when we look at timings of events, it takes 6 weeks in a human to remove from a pimordial to a pre-antral follicle
  • it takes another month for that follicle to evolve from being a pre-antral follicle to an antral follicle
  • so in total = 3 months
  • 3 months for primordial follicle to wake up and go through to ovulation
  • most of them will not make it
82
Q

Human folliculogenesis timetable

(picture)

83
Q

Human folliculogenesis takes

A

12 weeks

  • 6 weeks primordial to pre-antral
  • 4 weeks pre-antral to antral
  • 2 weeks antral to graffian/ovulatory
  • primordial follicle - 3 months ago will start developing
  • in this specific ovarian cycle, all that will happen pre-ovulation, all that will happen is the progression from antral to an ovulatory follicle
  • the last 2 weeks occur this month - the rest occurred 3 months ago
84
Q

Human folliculogenesis

(follicles)

A

primordial follicle

  • oocyte + single layer of granulosa cells

pre-antral follicle

  • oocyte + multiple layers of GC

antral follicle

  • multiple layers of GC and theca cells + antrum

graffian/ovulatory ollicle

  • multiple layers of GC and TC + single large antrum
85
Q

The ovarian cycle

progression

A
  • the progression from FSH dependence to LH dependence
  • that late ovulator follicle depnds on LH, s does the corpus luteum
  • the corpus luteum lives for 2 weeks - dies in the following month
  • that progression through corpus albicans happens after the cycle finishes
  • functional luteolysis - stops making progesterone
  • structural luteolysis - then becomes corpus albicans and dies
86
Q

The ovarian cycle

progression

(picture)

Reproductive and Developmental Biology (8 decks)

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