Folliculogenesis Flashcards

1
Q

Name 5 things that have to be achieved in order to be able to reproduce

A
  • sexual differentiation
  • sexual maturation
  • production, storage and release of sufficient supply of eggs and sperm
  • correct number of chromosomes in eggs and sperm (haploid - 23 otherwise there will be aneuploidy)
  • eggs and sperm have to meet
  • creation of new individual from genes from each parent
  • to nurture individual until capable of independent life
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2
Q

What are primordial germ cells?

A
  • cells that will become eggs or sperm
  • first identifiable in the yolk sac of the developing foetus at 3 weeks after conception
  • undergo many cycles of mitosis and then migrate to the genital ridge of the foetus
  • this genital ridge then becomes the gonad
  • further differentiation of the PGC depends on the development of the gonad (ovary or testis)
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3
Q

What is the cell lineage of primordial germ cells in females?

A
  • PGCs
  • if they go to the ovary, they become oogonia
  • these are egg-precursors which are diploid and multiply by mitosis. Once this stops, they enter meiosis and become primary oocytes
  • these get surrounded by granulosa cells to make the primordial follicles
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4
Q

How many oocytes to females have before vs after birth?

A
  • before = about 7 million
  • lots apoptose before birth, so left with about 500,000
  • through puberty and up to menopause, this number declines
  • cannot make anymore after birth
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5
Q

How are chromosomes duplicated?

A
  • chromosomes replicate during S-phase of the cell cycle
  • they remain attached at the centromere
  • each copy is a chromatid, the two copies are identical and so known as sister chromatids
  • during mitosis, spindles attach to these and pull them apart, producing two identical chromosomes
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6
Q

Meiosis overview

A
  • There is a replication of chromosomes
  • Unlike mitosis, this involves two divisions
  • 1st - chromosome number is reduced as each homologous chromosome pair is separated into two different cells, leaving each one with a member of each of the homologous pair
  • 2nd - the replicated chromatids of each chromosome are separated
  • meiosis begins with one diploid cell, and two divisions later gives 4 haploid cells
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7
Q

Why is there an uneven division of cytoplasm during cytokinesis?

A
  • After first division, there is the secondary oocyte and the first polar body
  • in the second division, the polar body produces two polar bodies, and the secondary oocyte produces the mature ovum and a third polar body
  • there is this uneven division as the mature ovum needs as much cytoplasm and cellular machinery as possible, it doesnt need to waste it in the polar bodies
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8
Q

Why are oocytes vulnerable in meiosis I?

A
  • chromatids are lined up on the spindle
  • there is more risk of chromosome abnormalities if there are errors in spindle dividing - don’t get proper movement of chromosomes - more or less in one of the divided cells than the other
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9
Q

How are the oocytes protected as the primordial follicle?

A
  • each becomes surrounded by protective layers and cells
  • in the foetal ovary, the surrounding cells condense around the oocyte and differentiate into the granulosa cells
  • these granulosa cells then secrete an acellular layer called the basal lamina
  • the whole structure is called the primordial follicle
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10
Q

What are the first stages in folliculogenesis?

A
  • as the follicles start to grow, the granulosa cells multiply and the oocyte secretes another protective acellular layer called the zona pellucida - which stays attached after ovulation
  • once growth of the follicles has started, a second layer of cells then differentiate around the basal lamina - the theca, which becomes vascularised
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11
Q

Is folliculogenesis driven by FSH?

A

YES

  • but early growth is independent of FSH and driven by other local factors
  • we can see this in FSH-deficient patients and people on the COCP, where the follicles will continue early growth, but then die
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12
Q

What happens as the follicle continues to grow?

A
  • It rapidly increases in diameter and granulosa cell divisions increase
  • Gaps begin to form in the granulosa cell layers
  • these gaps consist of flud-filled space which form an antrum
  • follicles with an antrum are known as antral or secondary follicles
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13
Q

How does the antrum develop?

A
  • gaps begin to form in the granulosa cell layers
  • these are initially found when the follicle is around 0.2-0.4mm
  • these join and make a larger, single antrum at 0.4-0.9mm
  • as the follicle grows, the antrum grows and displaces the oocyte to one side
  • the follicle can get 2-20mm, with the antrum displacing the oocyte to the side
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14
Q

How do we classify follicles?

A
  • Preantral or primary
  • antral or secondary (has an antrum)
  • preovulatory or Graafian (has an antrum, basal lamina, theca etc)
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15
Q

What are the stages of follicle growth?

A
  • Start off with a resting follicle
  • unknown factors trigger the initiation to grow into a preantral (larger) follicle
  • these two steps are FSH independent and take around 65 days
  • when they reach a certain size, they are recruited into the cycle
  • from these, one is selected to be the dominant follicle, which multiplies a lot and pumps out a load of oestrogen - this is destined to be ovulated
  • this process of recruitment to selection takes 15 days and is FSH/LH dependent
  • The egg that is ovulated will have started its growth about 3 months ago
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16
Q

What is the 2 cell, two gonadotrophin theory?

A
  • Theca cells produce androgens. Granulosa cells produce oestrogens
  • machinery required for cholesterol to androstenedione and testosterone conversion is only present in the theca
  • Aromatase, required to convert androstenedione to oestrone, is only present in the granulosa cells
  • You only have LH receptors on the theca and FSH on the granulosa (however at a much later stage, the granulosa cells can produce LH receptors too)
  • so LH causes androgen production, which go into the circulation and to the granulosa cells, to be converted to oestrogen
17
Q

How are the hormones produced from cholesterol?

A
  • Sequential removal of C atom from cholesterol
  • different enzymes at different stages
  • enzymes that an convert cholesterol to androgens are present in the theca
  • then androgens from theca are converted to oestrogens via aromatase inn the granulosa
  • however at a later stagem the granulosa cells will acquire LH receptors so they can make progesterone from cholesterol
18
Q

How is folliculogenesis controlled?

A
  • GnRH acts on the pituitary to produce LH/FSH
  • By stimulating the theca and granulosa you produce androgens, oestrogens and progesterone, which will act on the hypothalamus and pituitary in a negative feedbacl