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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
What feature of the Anteroventral periventricular nucleus (AVPN) separates it amongst males / females?
Sexually dimorphic (way more in females)
26
What type of GnRH release is the AVPN for? What is the resulting function?
GnRH / LH Surge Important for Ovulation.
27
What gene is responsible for Kisspeptin transcription?
Kiss1
28
In K/O studies, what 2 phenotypes occur when Kiss1 is removed?
Failure of sexual maturation Infertility
29
Kisspeptin therapy in juvenile rats results in what change?
Advances timing of puberty
30
What receptor does Kisspeptin target? Where are they found?
GPR54 receptor Expressed within GnRH neurones
31
What 3 domains make up G-protein coupled receptors?
Ectodomain (-NH2 / outside) Transmembrane domain Cytoplasmic (-COOH / inside)
32
G-protein's consist of how many sub-units? What are their names?
3 Alpha / Beta / Gamma
33
When activated, what subunit dissociates away from the receptor?
Alpha subunit
34
What three alpha subunits are important in reproduction?
G(alpha)Q G(alpha)S G(alpha)I
35
What occurs in response to the activation of G(alpha)Q?
Activation of phospholipase C
36
What occurs in response to the activation of G(alpha)S?
Activation of adenylate cyclase
37
What occurs in response to the activation of G(alpha)I?
Inhibition of adenylate cyclase
38
What alpha subunit is the GPR54 receptor?
GaQ
39
Children with mutations in the GPR54 have what phenotype?
Delayed puberty
40
What hormone is responsible for regulating GPR54 / Kisspeptin?
Leptin
41
Kiss1 neurones express what important receptor?
Leptin receptor
42
GPR54 k/o animales fail to attain ... ?
Puberty
43
What phenotype is witnessed when GPR54 mutations occur?
Hypogonadotropic hypogonadism
44
How does sexual dimorphism in the AVPN occur?
Early in gestational life, testosterone presence removes neuronal setting which enables estrogen-positive feedback. K/O of testosterone mice feminises AVPN.
45
What cells within the anterior pituitary produce LH / FSH?
Gonadotrophs
46
What two subunits make up FSH / LH?
Alpha | Beta
47
Which sub-unit is the same in the glycoproteins LH / FSH?
Alpha
48
What is the role of the Beta-subunit that is in FSH / LH?
Confers specificity to respective receptors.
49
What feature of GnRH will favour the production of FSH or LH?
Pulse frequency
50
Slow GnRH pulse frequency produces which gonadotropin?
FSH | S for SLOOWWW
51
Fast GnRH pulse frequency produces which gonadotropin?
LH
52
How is FSH released into circulation?
Constitutively - little storage capacity, released on production.
53
How is LH released into circulation?
First packaged into granules then exocytosed when GnRH stimuli arrives. (held near capillary wall)
54
What storage protein is LH packaged in vesicles with?
Secretogranin II
55
What are the 3 regulatory programmes required for follicular development?
FSH LH Follicle itself (oocyte + somatic cells)
56
Why are the presence of somatic cells so important for follicular development?
Oocyte doesn't have receptors, so somatic cells have to transmit signals from ant. pituitary.
57
What are the 4 steps that make 'primordial follicles'
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
How many primordial follicles exist at birth?
1,000,000
59
What study / experimental procedure showed oogonal stem cells being present in adult ovary? **Potential therapeutic target**
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
At what stage of meiosis are primordial / primary / secondary / tertiary follicles arrested at?
Prophase of Meiosis 1
61
What 2 features constitute the primordial follicle?
``` Primary oocyte Granulosa cells (squamous) ```
62
What 3 features constitute the primary follicle?
Primary oocyte Granulosa cells (CUBOIDAL) ZONA PELLUCIDA
63
What 4 features constitute the secondary follicle?
Primary oocyte Granulosa cells (multiple layers) Zona pellucida THECA (Interna & externa)
64
What follicular stages characterise 'early follicular stage'?
Primordial Primary Secondary
65
What feature separates the early follicular stage from the 'late follicular stage'?
Early follicular stages are Gn-INDEPENDENT.
66
What 2 groups of factors promote development along the early follicular phase?
Oocyte-secreted Factors (OSFs) (members of TGF-Beta family) Granulosa Cell factors
67
Name two important OSFs
GDF 9 (Growth differentiation factor 9) BMP 15 (Bone morphogenic protein 15)
68
Name two granulosa cell factors involved in folliculogenesis
Kit ligand AMH (Anti-mullerian Hormone) [suppresses]
69
What is the clinical relevance of AMH?
Indicator to fertility lifespan. Low AMH means NOT MUCH SUPPRESSION, so more follicles released = earlier menopause.
70
Tertiary follicles are also known as 'what' follicles?
Antral follicles
71
What feature of tertiary follicles differentiates them from the 'early follicular' counterparts?
FSH-dependent
72
What happens to the granulosa cells in follicular progression from the secondary into the tertiary phase?
Differentiate into: ``` mural granulosa (edge) cumulus granulosa (oocyte) ```
73
What structure forms as a result of granulosa cell secretions?
Antral cavity (fluid filled)
74
What structure doesn't develop in FSH-Beta k/o mice?
Antral cavity
75
What is one really important feature of tertiary follicles? They are now capable of producing what?
Sex steroids
76
Thecal cells express what receptor?
LH-receptor
77
Thecal cells produce what hormone?
Androgen
78
Granulosa cells express what receptor?
FSH-receptor
79
How do androgens get from the thecal cell to the granulosa cell?
Diffusion (lipid-based)
80
What enzyme is situated in granulosa cells?
Aromatase
81
The conversion of androgen --> 17B-estradiol occurs in which follicular cell?
Granulosa cell
82
FSH and LH receptors have what alpha subunit?
GalphaS
83
Oocyte secreting factors work through activating which signalling molecules?
SMAD | move to nucleus and act as transcription factors
84
What 5 effects do OSFs have on granulosa cells?
1) Proliferation 2) Differentiation (mural / cumulus) 3) Stimulate matrix production 4) Estradiol production 5) Stimulate metabolism
85
What 3 nutritive functions does the oocyte rely on surrounding granulosa cells for?
1) Glycolysis (occurs in granulosa cells then products transported into oocyte) 2) Amino acid uptake (e.g. alanine) (requires transporters) 3) Cholesterol production
86
What is the reason for why the oocyte is so incapable of metabolic processes?
Avoid oxidative stress by outsourcing all catabolic processes.
87
What cell is responsible for maintaining meiotic arrest of the oocyte?
Granulosa cell
88
What two compounds does the granulosa cell provide the oocyte with to maintain meiotic arrest?
cAMP | cGMP
89
What is the mechanism through which granulosa cells inhibit the progression of meiosis?
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
Through what structure does granulosa cell provide cAMP / cGMP / nutrients?
Gap junction
91
What component of the gap junction is particularly important for GJ formation?
Connexin 43
92
What is the name of the oocyte stem cell?
Oogonium
93
What stage of meiosis is the secondary oocyte arrested at?
Metaphase II
94
What are the pockets of follicular fluid within the late, secondary follicle made of?
Hyaluronic acid
95
What effect does low estrogen levels have on hypothalamus / pituitary?
Inhibitory
96
High levels of estrogen result in what change and what effect?
Positive feedback on hypothalamus HIGH FSH and LH
97
Why is there only an LH surge in response to positive feedback on GnRH?
Inhibin is also released from the tertiary follicle and inhibits FSH
98
What is the importance of pulsatility in regards to GnRH release?
Inhibits downregulation of GnRH
99
Slow pulsatile release occurs at what rate?
every 2-3h
100
Fast pulsatile release occurs at what rate?
<1h
101
What two mechanisms can confer specificity to which gonadtrophin hormone is produced?
Pulsatility Release mechanism
102
What is the corona radiata?
The single layer of granulosa cells that surrounds the zona pellucida
103
What is the mechanism of FSH stimulating granulosa cells to produce estradiol?
Activates aromatase enzyme

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