Folliculogenesis Flashcards

1
Q

What are the main stages required for human reproduction to occur?

A

Differentiation into male or female

Sexual maturation

Production, storage and release of sufficient supply of eggs and sperm

correct number of chromosomes in eggs & sperm

Eggs and sperm have to meet ie. gamete transport

Creation of new individual with genes from both parents

To nurture individual until capable of “independent life”

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2
Q

How do germ cells enter the gonad?

A

PRIMORDIAL GERM CELLS
= precursors for eggs/sperm

  • PGCs found in yolk sac at 3 weeks gestation
  • PGCs undergo mitosis cycle
  • migrate to genital ridge in foetus
  • genital ridge then becomes the gonad
  • Differentiation of the PGC into gametes (M/F) depends on sexual differentiation of the gonads
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3
Q

What happens when PGCs enter the ovary?

A

PGCs = primordial germ cells
They become OOCYTE IN THE OVARY

  • become oogonia in the ovary
  • oogonia are precursors to the egg, are diploid and therefore multiple my mitosis
  • when mitosis stops, they enter meiosis (PRIMARY OOCYTES)
  • once they enter meiosis, cells become quiescent (arrest in G0)
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4
Q

What is the ‘Ovarian reserve’?

A

idea that all the eggs a woman will ever have are made within gestation of that foetus

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5
Q

What happens when oogonia enter meiosis I?

A

no more division occurs
become primary oocytes
these remain arrested in G0 until ovulated (and then fertilised)

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6
Q

What are the 4 main stages of mitosis?

A

prophase
metaphase
anaphase
telophase

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7
Q

What is meiosis?

A

2 divisions

meiosis I: similar to mitosis, duplication and separation of chromosomes (4n -> 2x 2n)

meiosis II: further division of 2n cells -> 2x n (haploid gametes are result)

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8
Q

What is the structural difference between mitosis vs meiosis and meiosis I vs meiosis II?

A

chromosomal alignment

meiosis I: sister chromatic pairs line up at equator

meiosis II: individual chromatids line up at the equator

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9
Q

What is the follicle?

A

egg surrounded by a single layer of granuloma cells

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10
Q

What is distinct about the divisions in oogenesis?

A

unequal division of cytoplasm during cytokinesis

produces daughter cell and polar body

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11
Q

What is the function of the retained cytoplasm in the main egg (in oogenesis)?

A

used for nutrition

helps development of egg/embryo

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12
Q

Where are primary oocytes stored? How is the structure adapted to this?

A

packed into the outer layer of the ovary = CORTEX

Cortex is AVASCULAR - allows greater packing of primary oocytes here

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13
Q

What are the protective layers surrounding an oocyte in the ovary?

A
  • [in foetal ovary] surrounding cells condense and form GRANULOSA CELLS
  • granulosa cells secrete the BASAL LAMINA (acellular layer)

Together this is the PRIMORDIAL FOLLICLE

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14
Q

What is comprised in the primordial follicle?

A

oocyte + granuloma cells + basal lamina

[develops in foetal ovary]

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15
Q

How are the primordial follicles affected perinatally?

A

The number of primordial follicles postnatally determines the ovarian reserve and reproductive lifespan

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16
Q

What happens when the ovarian reserve of primordial follicles is depleted?

A

menopause

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17
Q

What is folliculogenesis?

A

growth and development of follicles

from the earliest stages in foetus to ovulation

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18
Q

What is the nature of follicular growth in ovaries?

A

most are NOT growing.

After puberty, a subset of follicles will start growing but v. slowly and tightly regulated

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19
Q

What happens when folliculogenesis begins after puberty?

A

granuloma cells multiply
oocytes secrete the ZONA PELLUCIDA (protein-rich acellular layer)
ZP remains attached after ovulation

After initiation of follicular growth, a second layer of cells differentiate around the basal lamina: the THECA

20
Q

How is the THECAL layer formed?

A

condensation of stromal cells surrounding oocyte

occurs at same time as formation of zona pellucida

21
Q

What is the regulation of follicle growth?

A

initiation of process and early stages are largely unknown

granuloma cells multiply 
oocyte enlarges (though still in meiotic arrest)
22
Q

What factors drive folliculogenesis?

A

GENERAL: FSH main regulator for folliculogenesis

early growth: FSH-independent, driven by local factors as cortex is avascular so no systemic hormone entry

late growth: FSH-dependent (astral follicles)

23
Q

What are the main stages occurring in follicular growth?

A

follicle rapidly increases in diameter + granulosa cells divide more
gaps form between granulosa cell layers
gaps = follicular fluid filled spaces, form an antrum
= antral follicles

24
Q

What are the 2 main types of follicles?

A

Pre-antral follicles (FSH-independent)

Antral follicles (FSH-dependent). Theca, which is vascularised, has formed by this stage, so hormones from systemic circulation can enter

25
Q

What are the (alternative) names for the different types of follicles?

A

Primary (Pre-antral)

Secondary (Antral)

Pre-ovulatory (Graafian)

26
Q

What stages produce an antral follicle?

A

migration of granulosa cells towards edge
formation of cumulus cells (surrounded by fluid filled antrum)
fluid is formed by transudate of the plasma (neoangiogenic capillaries) surrounding follicle

27
Q

What is an antral follicle?

A

contains cavity = antrum
antrum contains fluid formed as plasma exudate
FOLLICULAR FLUID = contains secretory products from oocyte and granulosa cells
asymmetric displacement of oocyte as antrum fills

28
Q

Which types of follicles are not visible by USS?

A

pre-antral follicles

but are present all the time until menopause

29
Q

What is follicular atresia?

A

death by apoptosis

regression following thinning of membrane and eventual death

30
Q

Which follicles undergo folliculogenesis?

A
  • cohort of early follicles, which leave the resting pool to grow (FOLLICLE INITIATION)
  • will not continue to grow unless they reach size at which they are FSH-sensitive (to changes in menstrual cycle) FOLLICLE RECRUITMENT
  • however only one follicle (DOMINANT FOLLICLE) will be selected for ovulation in one cycle
  • remaining follicles will die off by atresia
31
Q

How does the COCP affect folliculogenesis?

A

will have small follicles and will still grow

however lack of FSH mean that antral follicles are not ovulated and just die instead

32
Q

What is the function of the zona pellucida in fertilisation?

A

prevents further sperm entering (after one has got in)

therefore prevents POLYSPERMY and ANEUPLOIDY

33
Q

What hormone is produced by granulosa cells?

A

oestrogen

34
Q

What hormone is produced by theca cells?

A

androgens

35
Q

What is the importance of the vasculature in theca cells?

A

follicle can now be exposed to hormones that travel in the systemic circulation
e.g. FSH

36
Q

What is the 2-cell-2-gonadotrophin theory in folliculogenesis?

A

LH stimulates thecal cells to produce androgens
FSH stimulates granulosa cells to produce oestrogen from androgens (via aromatase)

only granulosa cells have aromatase - this is FSH-dependent

theca cells have only LH receptor

granulosa cells have both LH and FSH receptors

37
Q

What happens to androgens produced by theca cells?

A

may enter systemic circulation

or have autocrine effects on follicle

38
Q

When is the theca formed in folliculogenesis?

A

during the pre-antral stage

39
Q

What is the role of theca cells in steroidogenesis?

A

contains LH-R only

LH drives androgen and progesterone synthesis from theca

40
Q

What is the role of granulosa cells in steroidogenesis?

A

contain FSH-R: FSH drives oestrogen production in follicular phase of menstrual cycle

LH-R are acquired from the mid-follicular phase onwards (in dominant follicle)

LH then drives progesterone and oestrogen production too

41
Q

What is the HPG axis control of folliculogenesis?

A

hypothalamus: GnRH
pituitary: LH/FSH
ovary: oestrogen and progesterone

=> negative feedback on hypothalamus and anterior pituitary

42
Q

What occurs during ‘foetal development’ stage of folliculogenesis?

A

PGCs differentiate into oogonia
Proliferation by mitosis
Enter meiosis and arrest in G0
Form primordial follicles

43
Q

What occurs in the ‘postnatal stage’ of folliculogenesis?

A

Some basal growth of primordial follicles

But no further progression

44
Q

What occurs in the ‘post-pubescent stages’ of folliculogenesis?

A

[Once puberty commences]
Primordial follicles grow continuously until menopause
eggs remain arrested in meiosis I until ovulation
The egg then completes meiosis I, enters meiosis II and then arrests again (until fertilisation)

45
Q

What is aneuploidy?

A

high risk in older eggs (>35yo), presence of abnormalities in egg

e.g. defects in spindle proteins or abnormal chromosomal number

increased risk of complicated pregnancy or congenital issues