Folliculogenesis Flashcards

1
Q

What is required to reproduce?

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

What cells do oocytes or sperm differentiate from?

A

Primordial Germ Cells (PGCs)

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3
Q

When are PGCs first identified?

A

First identified in the yolk sac of the developing foetus three weeks after conception

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4
Q

Describe the cycle of primordial germ cells

A
  • Undergo many cycles of mitosis to increase the number of PGCs
  • They migrate to the genital ridge in the foetus
  • The genital ridge becomes the gonad
  • Further differentiation of the PGC into male/female gametes depends on the sexual differentiation/development of the gonads e.g into ovary or testes
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5
Q

What happens when PGCs enter the ovary?

A

Germ cells become oogonia when in the ovary

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6
Q

Describe what oogonia are?

A

Oogonia are egg-precursors that are diploid and multiply by mitosis

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7
Q

What is the process of oogonia to primary oocytes?

A
  • Oogonia are diploid and multiply by mitosis
  • Once mitosis stops they enter into meiosis and form primary oocytes
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8
Q

What is difference between male and female fertillity?

A

Women are born with an entire stock of eggs, when these are depleted we enter menopause

Men however do not have a defined fertillity

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9
Q

When are all the primary oocytes made?

Specify the particular stage.

A
  • They are made when the oogonia enters the 1st stage of meiosis
  • They remain in the first phase of meiosis until it is ovulated (or dies) - maybe up to 52 years
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10
Q

Explain the duplication of chromosomes

A
  • Chromosomes replicate during S-phase
  • Remain attached at the centromere
  • Each copy is known as a chromatid, the 2 are identical ‘sister chromatids’
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11
Q

Give a brief description of mitosis

A

Prophase, Metaphase, Anaphase and Telophase

  • DNA replication occurs in interphase and forms two sister chromatids which form a chromosome
  • Sister chromatids seperate and move to opposite ends of the cell
  • Spindle shorten pulling the sister chromatids apart to opposite poles
  • Cytokinesis the parent cell divides, forming two daughter cells.
  • Each daughter cell has two copies of each chromosome (46 chromosomes per cell)
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12
Q

Give an overview of meiosis

A
  • Chromosomes line up adjacent to each other (paternal and maternal chromosome 1 line up)
  • Homologous chromosomes pair and exchange genetic material = synapsis
  • First division - chromosome number is reduced as the two homologous pairs are seperated into two cells
  • Second division - the replicated chromatids of each chromosome are seperated
    • Meiosis begins with one diploid cell and ends up with four haploid cells
  • Both meiotic divisions has four stages similar to those in mitosis
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13
Q

What is the difference between oogenesis and folliculogenesis?

A

In oogenesis you will not get four mature eggs, but one mature egg with unequal division of cytoplasm during cytokinesis.

The rest is ejected as polar bodies

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14
Q

Describe the stages of oogenesis

A
  • Oogonium
  • Primary oocyte
  • Secondary oocyte
  • First polar body
  • Mature ovum and polar bodies
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15
Q

Summary of folliculogenesis

A
  1. Primordial follicle forms around the primary oocyte - making one of the first granulosa cell layers
  2. Granulosa cells secrete an acellular layer called the basal lamina
  3. Primary follicle secretes another protective layer called the zona pellucida - stays attached after ovulation + plays a role in fertilisation
  4. Tertiary (Graafian) follicle - theca cell layers, follicle fluid filled antrum and granulosa cell layers
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16
Q

What is follicle growth driven by?

A
  • Early stages of follicle growth are large unknown - granulosa cells multiply and oocyte enlarges (though remained in meiotic arrest)
  • FSH will drive mose of folliculogenesis but early growth is independant of FSH + driven by local factors
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17
Q

What proof is there that follicle growth is driven by FSH and local factors?

A

Early growth is driven by local factors due to

Follicle growth being present in

  • FSH-deficient patients or those with FSHr mutations
  • When FSH is supressed e.g on COCP the follicles continue early growth and then die
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18
Q

What happens when there is a gonadotrophin surge at the middle of the menstrual cycle?

A

Stimulates re-entry of the oocyte into meiosis as far as metaphase II

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19
Q

Why does the oocyte need to be surrounded by layers of cells?

A

Surrounded by layers of protective cells as they are the most important cell in the body

20
Q

What happens to the cells around the oocyte in the foetal ovary?

A

The surrounding cells condense around the oocyte and differentiate into granulosa cells

21
Q

What do the granulosa cells secrete?

A

An acellular layer called the basal lamina

22
Q

What is the structure of the primoridal follicle?

A

Granulosa cell and basal lamina

23
Q

What is the ovarian reserve?

A

Build up of the primordial follicles at the beginning of birth

24
Q

Folliculogenesis

A

The growth and development of follicles from the earliest ‘resting’ stages as laid down in the foetus, through to ovulation

25
Q

What happens during follicle growth?

A

Granulosa cells multiply and the oocyte will secrete another protective acellular layer called the zona pellucida - stays attached after ovulation

Second layer of cells then differentiate around basal lamina - called the theca

  • Theca has a blood supply allowing for influence of external hormonal influences
  • As follicle starts to grow it increases in diameter and granulosa cell divisions increase, gaps form in granulosa cell layers
    • Gaps consist of fluid flilled spaces forming an antrum and are filled with follicular fluid
26
Q

What is an antrum?

A

Gaps in granulosa cell layers consisting of fluid filled spaces with follicular fluid

27
Q

What divides the primary and secondary antral follicles?

A

Labelled by the presence or absence of an antrum

28
Q

Describe the antral follicle

A
  • Characterised by a cavity or ‘antrum’
  • Contains fluid formed exudate of plasma containing secretory products of oocyte and granulosa cell
  • Known as follicular fluid
  • As the follicular fluid volume and antrum expands the oocyte is displaced to one side
29
Q

Which follicles are not present on an ultrasound?

A
30
Q

Follicle initiation - what is it?

A

A cohort of early follicles leave the resting pool and grow continuously

31
Q

What is follicle recruitment?

A

The follicle will not continue to grow unless it reaches the sizr at which they respond to changes in FSH which occur in the menstrual cycle

32
Q

Why is only one follicle recruited?

A

The human pelvis is only designed to carry a single foetus therefore only one will be selected for ovulation

33
Q

How many cycles does it take for a follicle to go from resting stage to ovulation?

A

3 cycles

34
Q

What parts of the cycle are gonadotrophin independant?

A

Primordial and pre antral

35
Q

What parts of the cycle are gonadotrophin dependant?

A

Antral + Ovulatory

36
Q

Describe the structure of the antral ovarian follicle

A
  • Oocyte with cumulus cells surrounding it
  • Follicular fluid
  • Granulosa cell layer
  • Basement membrane
  • Theca layer
37
Q

Why is the theca vasculature important?

A

Theca vasculature brings all the circulating influences particularly FSH and LH

38
Q

What does the ovarian follicle produce?

A

Produces steroids

39
Q

What is the 2-cell, 2-gonadotrophin theory?

A
  • LH will bind to LH receptors on the theca cell = produces androgens and progesterone
  • The granulosa cell layer will convert these to oestrogens which have FSH receptors and FSH will bind and stimulate aromatase
40
Q

Describe how LH stimulates theca cells?

A

It binds to the LH receptor which stimulates the theca cell to turn cholesterol to androstenedione which is then released into the circulation

41
Q

How does FSH stimulate granulosa cells?

A
  • Androstenedione diffuses into the granulosa cell
  • FSH binds to the FSH receptor
  • Aromatase converts androstenedione into estradiol that is then released into the follicle
42
Q

What receptors do theca cells have?

A

LH not FSH receptors

43
Q

Which receptors do granulosa cells have?

A

Have FSH receptors and LH receptors

44
Q

Why are LH receptors needed on granulosa cells?

A
  • They are acquired from mid-follicular phase on
  • The LH will drive progesterone and oestrogen production as well
45
Q

How is folliculogenesis controlled?

A
  • Hypothalamus releases GnRH into the anterior pituitary
  • This then produces FSH/LH which stimulates the production of oestrogen and progesterone
  • Then feedback influences the anterior pituitary and hypothalamus
46
Q

What happens to a follicle if it doesnt make it to the menstrual cycle?

A
  • Most will die through atresia, few make it into the menstrual cycle and even less ovulate
47
Q

Describe the summary of folliculogenesis

A
  • PGC differentiate into oogonia, proliferating by mitosis and enter into meiosis + meiotic arrest
  • These then form primordial follicles
  • There is basal growth of primordial follicles but these do not progress
  • Once puberty commences, primordial follicles initiate growth as a continuum, until all follicles depleted and woman enters into menopause
  • Eggs remain arrested in M1 until ovulation
  • They then enter into M2 and arrest again