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HRM > 1 - The Menstrual Cycle Overview / Folliculogenesis > Flashcards

1 - The Menstrual Cycle Overview / Folliculogenesis Flashcards

1
Q

What are the names of the two aspects to the menstrual cycle?

A

1) Ovarian cycle

2) Uterine cycle

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2
Q

What are the 2 functions / end-goals of the menstrual cycle?

A

1) Transport gametes to the site of fertilisation

2) Provide suitable site for implantation

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3
Q

What process occurs if fertilisation fails?

A

Menses (endometrial shedding)

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4
Q

What are the 3 phases to the uterine cycle?

A

1) Menstrual phase
2) Proliferative phase
3) Secretory phase

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5
Q

What days in the uterine cycle does the ‘menstrual phase’ take place?

A

Days 1-5

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6
Q

What days does the ‘proliferative phase’ take place during the uterine cycle?

A

5-14

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7
Q

What days does the ‘secretory phase’ take place during the uterine cycle?

A

14-28

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8
Q

At what day in the ‘ovarian cycle’ does ovulation take place?

A

Day 14

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9
Q

What hormone predominates the follicular phase within the ‘ovarian cycle’?

A

Estrogen

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10
Q

What hormones predominates the luteal phase of the ‘ovarian cycle’?

A

Progesterone (+ estrogen)

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11
Q

What is the ‘oestrous cycle’?

A

Behavioural strategy to ensure mating occurs at the time of ovulation

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12
Q

What 3 aspects make up the ‘oestrous cycle’?

A

Attraction - more attracted to the male

Receptivity - more willing to accept male advances

Proceptivity - behavioural gesture to entice female (e.g. dancing)

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13
Q

What what point in human life does the menstrual cycle manifest?

A

Puberty

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14
Q

In the initiation of puberty, what hormone is FIRST produced within the hypothalamus?

A

Kisspeptin

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15
Q

Where does Kisspeptin act on and what hormone is stimulated ?

A

Acts WITHIN the hypothalamus.

Stimulates production of Gonadotrophin Releasing Hormone (GnRH)

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16
Q

Where is GnRH released from?

A

Neurones within the hypothalamus

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17
Q

Where does GnRH act? And what hormones are produced?

A

Acts on the ANTERIOR pituitary gland.

Produces gonadotrophins (LH and FSH)

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18
Q

What kind of feedback does estrogen have on GnRH in FEMALES?

A

Positive

AND

Negative

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19
Q

What kind of feedback does estrogen have on GnRH in MALES?

A

Negative

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20
Q

Define puberty

A

Immature individuals acquiring the physical and behavioural attributes that enable them to reproduce.

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21
Q

What controls the onset of puberty?

A

Genetics - most important

External factors (e.g. stressful events, relationships, adiposity)

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22
Q

What is the biggest external factor to pubertal initiation?

What evidence support this? Why?

A

Adiposity

Fatties have early puberty. Malnourished /athletes have late puberty.

Puberty is very energy-demanding process + LEPTIN LEVELS.

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23
Q

What two locations is Kisspeptin produced within the hypothalamus?

A

1) Arcuate nucleus

2) Anteroventral periventricular nucleus

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24
Q

What type of GnRH release is the arcuate important for?

A

Pulse generation

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25
Q

What feature of the Anteroventral periventricular nucleus (AVPN) separates it amongst males / females?

A

Sexually dimorphic (way more in females)

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26
Q

What type of GnRH release is the AVPN for? What is the resulting function?

A

GnRH / LH Surge

Important for Ovulation.

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27
Q

What gene is responsible for Kisspeptin transcription?

A

Kiss1

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28
Q

In K/O studies, what 2 phenotypes occur when Kiss1 is removed?

A

Failure of sexual maturation

Infertility

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29
Q

Kisspeptin therapy in juvenile rats results in what change?

A

Advances timing of puberty

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30
Q

What receptor does Kisspeptin target? Where are they found?

A

GPR54 receptor

Expressed within GnRH neurones

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31
Q

What 3 domains make up G-protein coupled receptors?

A

Ectodomain (-NH2 / outside)

Transmembrane domain

Cytoplasmic (-COOH / inside)

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32
Q

G-protein’s consist of how many sub-units? What are their names?

A

3

Alpha / Beta / Gamma

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33
Q

When activated, what subunit dissociates away from the receptor?

A

Alpha subunit

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34
Q

What three alpha subunits are important in reproduction?

A

G(alpha)Q
G(alpha)S
G(alpha)I

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35
Q

What occurs in response to the activation of G(alpha)Q?

A

Activation of phospholipase C

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36
Q

What occurs in response to the activation of G(alpha)S?

A

Activation of adenylate cyclase

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37
Q

What occurs in response to the activation of G(alpha)I?

A

Inhibition of adenylate cyclase

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38
Q

What alpha subunit is the GPR54 receptor?

A

GaQ

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39
Q

Children with mutations in the GPR54 have what phenotype?

A

Delayed puberty

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40
Q

What hormone is responsible for regulating GPR54 / Kisspeptin?

A

Leptin

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41
Q

Kiss1 neurones express what important receptor?

A

Leptin receptor

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42
Q

GPR54 k/o animales fail to attain … ?

43
Q

What phenotype is witnessed when GPR54 mutations occur?

A

Hypogonadotropic hypogonadism

44
Q

How does sexual dimorphism in the AVPN occur?

A

Early in gestational life, testosterone presence removes neuronal setting which enables estrogen-positive feedback.

K/O of testosterone mice feminises AVPN.

45
Q

What cells within the anterior pituitary produce LH / FSH?

A

Gonadotrophs

46
Q

What two subunits make up FSH / LH?

A

Alpha

Beta

47
Q

Which sub-unit is the same in the glycoproteins LH / FSH?

48
Q

What is the role of the Beta-subunit that is in FSH / LH?

A

Confers specificity to respective receptors.

49
Q

What feature of GnRH will favour the production of FSH or LH?

A

Pulse frequency

50
Q

Slow GnRH pulse frequency produces which gonadotropin?

A

FSH

S for SLOOWWW

51
Q

Fast GnRH pulse frequency produces which gonadotropin?

52
Q

How is FSH released into circulation?

A

Constitutively - little storage capacity, released on production.

53
Q

How is LH released into circulation?

A

First packaged into granules then exocytosed when GnRH stimuli arrives.

(held near capillary wall)

54
Q

What storage protein is LH packaged in vesicles with?

A

Secretogranin II

55
Q

What are the 3 regulatory programmes required for follicular development?

A

FSH
LH
Follicle itself (oocyte + somatic cells)

56
Q

Why are the presence of somatic cells so important for follicular development?

A

Oocyte doesn’t have receptors, so somatic cells have to transmit signals from ant. pituitary.

57
Q

What are the 4 steps that make ‘primordial follicles’

A

1) Migration of primordial germ cells from YOLK SAC to FETAL OVARY
2) Mitosis but incomplete cytokinesis (forming germ cell cysts)
3) Oocytes enter meiosis (arrested in prophase of M1)
4) Breakdown of intracellular bridges + enclosure

= Primordial follicles

58
Q

How many primordial follicles exist at birth?

59
Q

What study / experimental procedure showed oogonal stem cells being present in adult ovary?

Potential therapeutic target

A

Anti-DDX4 antibody

Showed prescence of DDX4 (evolutionary-conserved germ-cell specific RNA helicase, only present in stem cells)

Labelled them (GFP)

Placed them back into ovarian biopsy

Produced primordial follicles.

60
Q

At what stage of meiosis are primordial / primary / secondary / tertiary follicles arrested at?

A

Prophase of Meiosis 1

61
Q

What 2 features constitute the primordial follicle?

A 
Primary oocyte 
Granulosa cells (squamous)
62
Q

What 3 features constitute the primary follicle?

A

Primary oocyte
Granulosa cells (CUBOIDAL)
ZONA PELLUCIDA

63
Q

What 4 features constitute the secondary follicle?

A

Primary oocyte
Granulosa cells (multiple layers)
Zona pellucida
THECA (Interna & externa)

64
Q

What follicular stages characterise ‘early follicular stage’?

A

Primordial
Primary
Secondary

65
Q

What feature separates the early follicular stage from the ‘late follicular stage’?

A

Early follicular stages are Gn-INDEPENDENT.

66
Q

What 2 groups of factors promote development along the early follicular phase?

A

Oocyte-secreted Factors (OSFs) (members of TGF-Beta family)

Granulosa Cell factors

67
Q

Name two important OSFs

A

GDF 9 (Growth differentiation factor 9)

BMP 15 (Bone morphogenic protein 15)

68
Q

Name two granulosa cell factors involved in folliculogenesis

A

Kit ligand

AMH (Anti-mullerian Hormone) [suppresses]

69
Q

What is the clinical relevance of AMH?

A

Indicator to fertility lifespan.

Low AMH means NOT MUCH SUPPRESSION, so more follicles released = earlier menopause.

70
Q

Tertiary follicles are also known as ‘what’ follicles?

A

Antral follicles

71
Q

What feature of tertiary follicles differentiates them from the ‘early follicular’ counterparts?

A

FSH-dependent

72
Q

What happens to the granulosa cells in follicular progression from the secondary into the tertiary phase?

A

Differentiate into:

mural granulosa (edge)
cumulus granulosa (oocyte)
73
Q

What structure forms as a result of granulosa cell secretions?

A

Antral cavity (fluid filled)

74
Q

What structure doesn’t develop in FSH-Beta k/o mice?

A

Antral cavity

75
Q

What is one really important feature of tertiary follicles? They are now capable of producing what?

A

Sex steroids

76
Q

Thecal cells express what receptor?

A

LH-receptor

77
Q

Thecal cells produce what hormone?

78
Q

Granulosa cells express what receptor?

A

FSH-receptor

79
Q

How do androgens get from the thecal cell to the granulosa cell?

A

Diffusion (lipid-based)

80
Q

What enzyme is situated in granulosa cells?

81
Q

The conversion of androgen –> 17B-estradiol occurs in which follicular cell?

A

Granulosa cell

82
Q

FSH and LH receptors have what alpha subunit?

83
Q

Oocyte secreting factors work through activating which signalling molecules?

A

SMAD

move to nucleus and act as transcription factors

84
Q

What 5 effects do OSFs have on granulosa cells?

A

1) Proliferation
2) Differentiation (mural / cumulus)
3) Stimulate matrix production
4) Estradiol production
5) Stimulate metabolism

85
Q

What 3 nutritive functions does the oocyte rely on surrounding granulosa cells for?

A

1) Glycolysis (occurs in granulosa cells then products transported into oocyte)
2) Amino acid uptake (e.g. alanine) (requires transporters)
3) Cholesterol production

86
Q

What is the reason for why the oocyte is so incapable of metabolic processes?

A

Avoid oxidative stress by outsourcing all catabolic processes.

87
Q

What cell is responsible for maintaining meiotic arrest of the oocyte?

A

Granulosa cell

88
Q

What two compounds does the granulosa cell provide the oocyte with to maintain meiotic arrest?

89
Q

What is the mechanism through which granulosa cells inhibit the progression of meiosis?

A

1) Granulosa cells give cAMP and cGMP
2) cGMP inhibits conversion of cAMP into 5’AMP
3) cAMP activates PKA
4) PKA activates Wee1
5) Wee1 phosphorylates MPF (CDK1 + CYB)
6) MPF inhibited

= Meiotic arrest

90
Q

Through what structure does granulosa cell provide cAMP / cGMP / nutrients?

A

Gap junction

91
Q

What component of the gap junction is particularly important for GJ formation?

A

Connexin 43

92
Q

What is the name of the oocyte stem cell?

93
Q

What stage of meiosis is the secondary oocyte arrested at?

A

Metaphase II

94
Q

What are the pockets of follicular fluid within the late, secondary follicle made of?

A

Hyaluronic acid

95
Q

What effect does low estrogen levels have on hypothalamus / pituitary?

A

Inhibitory

96
Q

High levels of estrogen result in what change and what effect?

A

Positive feedback on hypothalamus

HIGH FSH and LH

97
Q

Why is there only an LH surge in response to positive feedback on GnRH?

A

Inhibin is also released from the tertiary follicle and inhibits FSH

98
Q

What is the importance of pulsatility in regards to GnRH release?

A

Inhibits downregulation of GnRH

99
Q

Slow pulsatile release occurs at what rate?

A

every 2-3h

100
Q

Fast pulsatile release occurs at what rate?

101
Q

What two mechanisms can confer specificity to which gonadtrophin hormone is produced?

A

Pulsatility

Release mechanism

102
Q

What is the corona radiata?

A

The single layer of granulosa cells that surrounds the zona pellucida

103
Q

What is the mechanism of FSH stimulating granulosa cells to produce estradiol?

A

Activates aromatase enzyme

HRM (9 decks)

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