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Human Repro > Lecture 3 > Flashcards

Lecture 3 Flashcards

1
Q

GnRH

A

10 amino acids

acts at GnRH receptor – a GPCR that signals through Gαq

stimulates transcription FSH & LH

stimulates FSH & LH release

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2
Q

two modes of GnRH release:

A

pulses & surge

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3
Q

FSH & LH secretion from Anterior Pituitary

A

dimeric glycoproteins - a and B subunit

subunits identical; B-subunits confer hormone specificity

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4
Q

FSH domination

A

early follicular phase
stimulated by slow GnRH pulse frequencies
released through constitutive pathway

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5
Q

LH domination

A

late follicular phase
stimulated by fast GnRH pulse frequencies
packaged in electron-dense granules in association with storage protein secretogranin II

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6
Q

FSH/ LH release

A

movement of granules to cell membrane abutting a capillary - polarisation

GnRH -> Gaq -> PLC -> Ca2+ -> LH release

GnRH -> Gaq -> PLC -> PKA -> MAPK -> transcription -> FSH/ LH release

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7
Q

3 regulatory programmes for follicle development driven by

A

FSH
LH
Follicle (somatic cells and oocytes)

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8
Q

Follicular development

A

Primordial germ cells migrate from yolk sac to fetal ovary

Mitosis but incomplete cytokinesis: interconnected cells (germ cell cysts / nests)

oocytes enter meiosis (arrested in PROphase of meiosis I) breakdown of intracellular bridges enclosure of oocytes

primordial follicles (≈1x106 at birth)

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9
Q

oogonia stem cells

A

Isolated cells expressing DDX4 from human adult ovary using an anti-DDX4 antibody

DDX4 – DEAD box polypeptide 4; evolutionary conserved germ-cell specific RNA helicase

isolated cells mitotically active

labelled isolated cells with GFP

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10
Q

Primordial follicle

A 
Primary oocyte (MI prophase)
Granulosa cells (flat)
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11
Q

Primary follicle

A 
Primary oocyte (MI prophase)
Granulosa cells (cuboidal)
ZP
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12
Q

Secondary follicle

A 
Primary oocyte (MI prophase)
Granulosa cells (multiple layers)
Zona pellucida
Theca – interna & externa
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13
Q

activation is Gn-independent

A

Oocyte-secreted factors (OSF)
- members of TGFβ superfamily
GDF 9 (Growth Differentiation Factor 9)
BMP15 (Bone Morphogenic Protein 15)

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14
Q

Granulosa cell

A

kit ligand – promotes follicle development

AMH (Anti-Mullerian Hormone) – may restrain development

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15
Q

Tertiary follicle (antral follicles)

A 
Primary oocyte (MI prophase)
Zona pellucida
Theca – interna & externa
Granulosa cells – mural & cumulus
Antral cavity: absent in FSHβ k/o mice
Sex steroids
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16
Q

Early follicular phase

A

there are no sex steroids being produced
no negative feedback to the hypothalamus Slow pulses so AP produces FSH, some LH
FSH produces secondary follicles which can produce tertiary

17
Q

Sex steroid synthesis

A

acetate -> cholesterol -> pregnenolone

  • > progesterone / 17-hydroxypregnenolone
  • > DHEA -> androstenedione
18
Q

androstenedione

A

aromatase -> estrone

19
Q

testosterone

A

aromatase -> 17-estradiol

20
Q

Thecal cell

A 
LH binds to LHR 
Thecal cell releases androgens
androgens diffuse into granulosa cell 
FSH binds to FSHR 
granulosa cells have aromatase which binds to androgens to produce 17-estradiol
21
Q

FSH & LH Receptors

A

GPCRs

present on somatic cells in ovarian follicles (initially LH Receptor is only expressed on the thecal cells, but as it matures it then is found on the granulosa cells

generally coupled to Gs

activates adenylate cyclase

cAMP activates protein kinase A (PKA) - phosphorylation - Arg-Arg-X-Ser/Thr-X motif in proteins

e.g. enzymes in steroidogenesis
CREB -> nucleus

22
Q

OSF

A

Oocyte influences granulosa (cumulus) cell via OSF

bind to cell surface Ser/Thr kinases activate Smad signalling molecules
translocate to nucleus
act as transcription factors

23
Q

regulate granulosa cell

A

proliferation

differentiation

extracellular matrix production if ovulated so can stick to oviduct to move along

estradiol production

metabolism

24
Q

Cumulus cells influence oocyte

A

nutrients

meiotic arrest

25
Q

cAMP

A

cAMP -> PKA -> wee1 -> CyB+CDK1 (MPF inhibition) - ARREST

26
Q

cGMP

A

5’AMP - blocks cAMP

27
Q

Oocyte – granulosa cells co-operate to influence follicle development

A

Granulosa (cumulus) cells influence oocyte via gap junctions (GJ)

connexin 43 important in GJ formation

Human Repro (11 decks)

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