Folliculogenesis (repro) Flashcards

1
Q

Germ cells enter the gonad

A
  • cells that will become eggs or sperm originate from primordial germ cells (PGC)
  • PGCs first identifiable in yolk sac of developing foetus at 3 weeks after contraception
  • undergo many cycles of mitosis
  • migrate to genital ridge in foetus
  • genital ridge becomes the gonad
  • further differentiation of the PGC into male/female gametes depend on the sexual differentiation or development of the gonad ie into ovary or testis
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2
Q

Changes of PCGs in ovary

A

if PCGs enter the ovary they become oocytes:

  • germ cells become oogonia when in ovary
  • oogonia are egg-precursors, diploid and divide by mitosis
  • once mitosis stops, they enter into meiosis
  • they become primary oocytes
  • surrounded by layer of germ cells known as primordial follicle
  • establishment of the true ‘ovarian reserve’
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3
Q

Germ cells to eggs

A
  • all 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
  • primary oocytes are packed into the outer layer of the ovary (the cortex)
  • primary oocytes remain in first phase of meiosis until it is ovulated (or dies)
  • could be for 52 years
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4
Q

primordial follicle

A
  • oocytes are arguably the most important cell in body and are in vulnerable 1st meiotic phase for many years
  • therefore, each one becomes surrounded by protective layers and cells
  • in foetal ovary, surrounding cells condense around the oocyte and differentiate into granulosa cells (GC)
  • granulosa cells then secrete an acellular layer called the basal lamina (BL)
  • whole structure is called primordial follicle
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5
Q

Duplication of chromatids

A
  • chromosomes replicate during S phase of cell cycle
  • remain attached at the centromere
  • each copy known as a chromatid (2 copies are identical) and are sister chromatids
  • exact copy of original chromosomes
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6
Q

Overview of mitosis

A
  • mitosis broadly divides into 4 stages: (interphase), prophase, metaphase, anaphase, telophase
  • DNA replication during interphase forms 2 sister chromatids, which are banded together to form a chromosome
  • during mitosis, sister chromatids separate and move to opposite ends of the cell
  • During cytokinesis, the parent cell divides, forming two daughter cells
  • each daughter cell has 2 copies of each chromosome (homologous pairs)
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7
Q

Overview of meiosis

A
  • the diploid parent cell contains 2 homologous pairs of chromosomes
  • DNA replication during interphase forms 2 copies of each chromosome and the copies remain attached
  • during meiosis l, homologous chromosomes separate into 2 haploid cells, each containing one member of each homologous pair
  • oocyte is arrested in meiosis l
  • during meiosis ll, sister chromatids separate and four haploid daughter cells are formed that will develop into gametes
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8
Q

Folliculogenesis

A
  • defined as growth and development of follicles from earliest ‘resting’ stages as laid down in the foetus through to ovulation
  • most of follicles in ovary are not growing - after puberty a cohort of follicles initiate growth each day
  • as follicles start to grow, the granulosa cells (GC) multiply and the oocyte secretes another protective acellular layer called zone pellucida (ZP)
  • once growth of follicles has started a second layer of cells then differentiate around the basal lamina (BL), the theca which is vascularised
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9
Q

follicle growth

A
  • factors controlling initiation of growth and the early stages are largely unknown, but granulosa cells multiply and oocyte enlarges (though still in meiotic arrest)
  • FSH drives most of folliculogenesis but early growth is independent of FSH ie 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 cell layers
  • these gape consist of fluid-filled spaces which form an antrum and 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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10
Q

Classification of follicles

A
  • Antral or secondary
  • Preantral or primary
  • Preovulatory or Graafian
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11
Q

Antral follicle

A
  • Characterised by a cavity or ‘antrum’
  • contains fluid formed as exudate of plasma containing secretory products of oocyte and GC
  • known as ‘follicular fluid’
  • as follicular fluid volume and antrum expands, oocyte is displaced to one side
  • AF is visible on ultrasound
  • preantral follicles are not visible on ultrasound but are present all the time until menopause
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12
Q

Follicle initiation and recruitment

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

Theca cells and Granulosa cells

A
  • theca cells always have LHR and never FSHr
  • LH drives androgen and progesterone production from theca
  • granulosa have FSHr
  • FSH drives oestrogen production in follicular phase
  • LHR acquired from mid-follicular phase onwards (in DF)
  • LH will then drive progesterone and oestrogen production as well
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14
Q

Many follicles to one

A
  • thousands of primordial follicles
  • most die through atresia
  • a few make in into the menstrual cycle
  • even less actually ovulate
  • 99.999% die
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15
Q

Summary

A
  • PGCs differentiate into oogonia, proliferating by mitosis, and enter into meiosis and arrest
  • they then form primordial follicles
  • there is a bit of basal growth of primordial follicles (PF), but do not progress
  • once puberty commences, PF initiate growth as a continuum until all follicles are depleted and menopause has started
  • eggs remain arrested in meiosis l until ovulation
  • they then enter meiosis ll and arrest again
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16
Q

Glossary

A
  • Primordial Germ Cell (PGC) – precursor “stem” cells that will become either egg or sperm
  • Oogonia – precursors to eggs, they are diploid and multiply by mitosis
  • Primary oocytes – eggs that have entered meiosis and stopped at meiosis I
  • Secondary oocytes – eggs that have completed meiosis I, entered into meiosis II and stopped
  • Oogenesis – the process of egg development covering the stages from an immature oogonium to a mature ovulated egg ready for fertilization
  • Follicle – oocyte-containing structure containing several cell types i.e. granulosa and theca cells
  • Antrum – fluid-filled space in a follicle
  • Preantral follicle – follicle without an antrum consisting of various stages depending on number of layers of granulosa cells.
  • Antral follicle (AF) – follicle with an antrum filled with follicular fluid
  • Folliculogenesis – the process of follicle development covering the stages of growth from a resting primordial follicle to antral follicles and selection of the dominant follicle destined for ovulation
  • Sex steroids – large group of molecules derived from common sterol precursor: cholesterol. There are 4 main families of steroids – the progestogens; androgens; oestrogens (American spelling estrogen) and corticosteroids. Only the first three are defined as sex steroids. Within each family there are several members.