W4 - Folliculogenesis Flashcards

1
Q

How does the Germ cells enter the gonad?

A
  • Cells that will become eggs or
    sperm originate from primordial
    germ cells (PGC)
  • PGCs first identifiable in the yolk
    sac of the developing foetus at 3
    weeks after conception
    – Undergo many cycles of mitosis
    – They migrate to the genital ridge in
    the foetus
    – The genital ridge becomes the
    gonad
    – Further differentiation of the PGC into male/female gametes depend on the sexual differentiation/development of the gonad i.e. into ovary or testis
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2
Q

What happens if PGCs enter ovaries?

A
  • Germ cells become oogonia when in the ovary
  • Oogonia are egg-precursors, diploid and multiply by mitosis
  • Once mitosis stops and they enter into meiosis, known as primary oocytes
  • Surrounded by layer of GC – now known as primordial follicle
  • Establishment of the true “ovarian reserve”
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3
Q

How do Germ cells turn to eggs?

A
  • All the eggs that a woman will ever have are
    made at this stage
  • The mitotic divisions are therefore critical
  • Once the oogonia enter the 1st stage of
    meiosis no more division occurs and they
    become primary oocytes
  • The primary oocytes remains in the first phase
    of meiosis until it is ovulated (or dies)….maybe
    for 52 years!
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4
Q

How are primary oocytes packed?

A

Primary oocytes are packed into the
outer layer of the ovary: the cortex

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5
Q

What are primary oocytes?

A

Primordial Follicle
* Oocyte arguably the most important cell in the body and will
in the vulnerable 1st meiotic phase for many years
* Therefore each one becomes surrounded by protective layers
and cells
* In the foetal ovary, the surrounding cells condense around
the oocyte and differentiate into the granulosa cells (GC)
* The granulosa cells then secrete an acellular layer called the
basal lamina (BL)
* The whole structure is called the primordial follicle - you cannot be born with a naked oocyte.

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6
Q

How does the duplication of chromatids occur?

A
  • Chromosomes replicate during S-phase of cell cycle
  • Remain attached at the centromere
  • Each copy known as a chromatid → the 2 copies are
    identical to each other → “sister” chromatids
  • Exact copy of original chromosomes

In males, it would start with 1 diploid cell and make 4 haploid daughter cells. Oocytes is arrester in meiosis I and will stay there since ovulation.
In females, you have your oogonium and it becomes a primary oocyte. At its first meiotic division, it would divide into 2 daughter cells. There is unequal division of cytoplasm during cytokinesis after the first meiotic division. The smaller of the divisions will be called a polar body. In the second meiosis stage, there may not be other polar bodies being created, but there will be a mature egg.

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7
Q

What is Folliculogenesis?

A

The growth of the follicle.
* Defined as the growth and development of follicles from the earliest “resting” stages as laid down in the foetus, through to ovulation
* Most of the follicles in the ovary are not growing – after puberty a cohort of follicles initiate growth each day
* As the follicles start to grow, the granulosa cells (GC) multiply and the oocyte secretes another protective acellular layer called zona pellucida(ZP)
* Once growth of the follicles has started a
second layer of cells then differentiate around the basal lamina (BL): the theca, which is vascularised.

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8
Q

What is follicle growth?

A
  • The factors controlling initiation of growth and the early stages are
    largely unknown, but granulosa cells multiply & oocyte enlarges
    (though still in meiotic arrest)
  • FSH drives most of folliculogenesis but early growth is independent of
    FSH i.e. driven by local factors
    – Apparent in FSH-deficient patients or those with mutations of FSHr
    – Also means that even when FSH is suppressed eg. on COCP, the follicles will still
    continue early growth but then die
  • As follicle starts to grow it increases rapidly in diameter and granulosa
    cells divisions increase, but gaps begin to form in the granulosa cell
    layers
  • These gaps consist of fluid-filled spaces which form an antrum & are
    filled with follicular fluid
  • 2 main phases of follicle growth labelled by absence or presence of
    antrum
  • Follicles with an antrum are known as antral or secondary follicles
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9
Q

How do you classify follicles?

A
  • Prenatal or primary follicles
  • Antral or secondary follicles
  • Preovulatory or Graafian follicle
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10
Q

What are Antral follicles?

A

*Characterised by a cavity or “antrum”
*Contains fluid formed as exudate of plasma containing secretory products of oocyte & GC
*Known as “follicular fluid”
*As follicular fluid volume and antrum expands, oocyte is displace to one side

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11
Q

How is AF visible on ultrasound?

A

Pre-antral follicles are NOT visible on u/s but are
present all the time until menopause
You can tell dominant healthy follicle with antral follicles as small black spaces.

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12
Q

Basically, what is follicuogenesis?

A

*A cohort of early follicles
leaving the resting pool and
grow continuously
*This is known as follicle
initiation
*They will NOT continue to
grow unless they reach the
size at which they respond to
changes in FSH that occur in
the menstrual cycle
*This is known as follicle
recruitment
*Human pelvis designed in
general to carry a single
foetus therefore,
–From the group that are
recruited only one will
subsequently be selected
for ovulation

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13
Q

What are the stages of follicle growth?

A

Primordial follicle - about 0.02mm
This turns to prenatal follicle with BL and thecca cells etc but no antrum - 0.2mm
These two stages can take 65+ days and does not need Gonadotrophin.
It then forms a small astral - 2mm. This growth needs FSH
From this cohort, one is chosen to become the dominant follicle to ovulate. These stages are gonadotrophin dependent.

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14
Q

What are the features of the antral ovarian follicle?

A
  • Follicular fluid
  • Basement membrane
  • Theca layer
  • Cumulus cells
  • Granulosa cells
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15
Q

Why is the theca vasculature important?

A

This means the follicle is now open to influence from the surrounding environment. Anything produced by the follicle can now enter into vascular.

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16
Q

How does the ovarian follicle produce steroids?

A

Theca cells will produce androgens starting with cholesterol. This conversion of androgens to cholesterol is driven through the binding of LH to LH receptors located on the Theca cells.

Granulosa cells takes these androgens and converts them to Estradiol. This is done via the aromatase enzyme. This conversion is driven by FSH binding to the. FSH receptor. These receptors are only found on granulosa cells.

These two cells both being required has lead to the 2-cell, 2-gonadotrophin theory. Anything produced by these two cells can also be taken out into the circulation.

17
Q

How does LHR and FSHR link to Theca Cells and Granulosa cells?

A

Theca cells:
Cholesterol is converted into pregnenolone by the P450scc cleavage enzyme. This can then go into 2 pathways.
1) Can be covered into 17-hydroxypregnanalone via P45017a hydrolase. This is then converted to DHEA via P45012a lyase, which is then converted to androsteindiol. These are then interconverted to testosterone and andosteronedione.

2) Can be metabolised into the delta4 pathway to create progesterone then 17 hydroxy progesterone.

Driven by LH

Granulosa cells:
Driven by FSH
FSH drives estrogen production in follicular phase.

There is only one instance where LH is present in Granulosa cells and that is when there is dominant selection. This allows it to make progesterones.

18
Q

What happens to the primordial follicles?

A

Thousands of primordial follicles…most die
through atresia, a few make it into the menstrual
cycle & even less ovulate