L7: Ovary 2: Oocyte and Ovulation Flashcards

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1
Q

What happens to oocyte during follicle development?

A
  • it maintains meiotic arrest
  • but at same time, it develops the competence to resume meiosis later
  • it grows, and acquires more components as it grows
  • it undergoes genomic imprinting
  • around the time of ovulation, it resumes meiosis
  • crucially, it acquires developmental competence (ability to support the development of a viable embryo and then healthy individual if fertilised)
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2
Q

What is germinal vesicle?

A

Simply the term for the nucleus of an oocyte

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3
Q

What is nuclear maturation of an oocyte?

A

only processes within germinal vesicle (GV)

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4
Q

What is cytoplasmic maturation of an oocyte?

A

Excludes processes within GV

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5
Q

What is zona pellucida?

A

Specialised ECM formed from secretion from the oocyte and surrounding granulosa cells (both cell types are needed!)

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6
Q

When is zona pellucida formed?

A

As follicles start to grow

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7
Q

What is zona pellucida made of?

A

Repeating dimers of ZP2 and ZP3 linked together by occasional cross-linking of ZP1

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8
Q

How is ZP3 important?

A

At fertilisation ZP3 is key - stops polyspermy

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9
Q

Why does oocyte accumulate mRNAs and organelles as it grows?

A
  • the oocyte is in meiotic arrest, with an extra set of all chromosomes, and so has four copies of each chromosome.
  • While meiosis is arrested, the chromosomes themselves are active, including mRNA production and transcription of proteins.
  • Some proteins are used as the oocyte grows, other mRNAs and proteins are used only after fertilisation, providing a maternal source of RNAs that can support the embryo until its own genome is activated.
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10
Q

What are the cytoplasmic organelles of an oocyte?

A
  • mitochondria
  • lipids
  • cortical granules
  • vesicles
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11
Q

How is mitochondria important for an oocyte?

A
  • site of energy production
  • circular DNA, high mutation rate (particularly susceptible to reactive oxygen species - likely why mitochondria from sperm do not contribute to embryo)
  • as mammals become older, mitochondria in oocytes become increasingly vacuolated - poor quality - and reduced in number
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12
Q

What is mitochondrial bottleneck?

A

Each oocyte inherits only a small proportion of a female’s mitochondria: has important implication in mitochondrial diseases, depending on the mitochondrial DNA that the oocyte receives –> depends the severity of the disease
That’s why three parent embryos created, also with mitochondrial DNA, so diseases not inherited
- As PGCs are dividing at each division you will only get a few mitochondria going into oocytes – bottleneck

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13
Q

How are cortical granules important for an oocyte?

A

secretory organelles produced by Golgi, needed to block polyspermy along with ZP3

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14
Q

How is the interaction between oocyte and granulosa cells important?

A

Now very clear that both cell types (granulosa and oocyte) are dependent on each other for their development.
Oocyte regulates:
- differentiation,
- follicle organization,
- steroidogenesis,
- proliferation,
- expansion.
Granulosa cells regulate:
- meiotic arrest,
- oocyte growth,
- metabolic substrates,
- meiotic maturation.

Without granulosa cells the oocyte doesn’t stay in meiotic arrest.

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15
Q

How do granulosa cells and oocyte communicate?

A

Via gap junctions - collections of intracellular channels

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16
Q

What are gap junctions composed of?

A

12 connexins - six coming from each of the two contacting cells.
Cx43: granulosa cell to granulosa cell
Cx37: granulosa cell to oocyte

17
Q

What is the function of gap junctional communication?

A

Supports metabolism and prevents meiotic resumption (keep oocyte in meiotic arrest), removal of granulosa cells leads to resumption of meiosis

18
Q

Where are the oocyte-granulosa cell gap junctions located?

A

They sit on unusual structures called trans-zonal projections, that go between the oocyte and the granulosa cells

19
Q

What is genomic imprinting of oocytes?

A

Usually we have two copies of each gene (other than XY sex chromosomes)
But not all genes are equally transcribed across the two copies!
Happens with key developmental genes (only small amount of genes). Expression of one copy of the gene is usually repressed, this happening either in the sperm or in the egg (during sperm or egg development)

20
Q

At which stage of meiosis does meiotic arrest take place? When does meiotic arrest take place?

A

Oocytes held in meiotic arrest (at dictyate stage of Prophase 1) from time of follicle formation (before birth) all the way through to ovulation

21
Q

What maintains meiotic arrest?

A
  • Activation of GPCRs on the oocyte leads to production of cAMP, keeping levels high, resulting in downstream pathway together maintaining meiotic arrest.
  • The oocyte needs to maintain high levels of cAMP (dependant on granulosa cells, that gap junction lets keep high levels of cAMP) if cAMP levels fall, they resume meiosis
22
Q

What happens to meiotic arrest as ovulation approaches?

A

GPCR receptors are no longer activated, production of cAMP falls, downstream pathway no longer stimulated. Meiosis resumed

23
Q

What is the function of polar bodies?

A

Is not clear, one theory was that it was used for defective chromosomes to be thrown out, however Ma et al. showed that the chromosomes in an egg were not defective.

24
Q

What is the usual sign that meiosis has resumed?

A

Germinal vesicle breakdown

25
Q

What are the steps of an oocyte once it ovulates? What is the sequence of these events?

A
  1. resume meiosis
  2. get fertilised
  3. undergo early cell divisions
  4. implant
  5. continue to develop properly to the stage of birth

it turns out that it acquires the ability to carry out these processes step-by-step, and in the same order that it will later fo on to do them (if it is ovulated)

26
Q

What happens to a follicle as ovulation approaches?

A
  • Antrum enlarges (cumulus cell expand) and pre-ovulatory follicle diameter increases.
  • cumulus cells secrete hyaluronan in response to factors secreted from the oocyte (GDF9 and BMP15)
27
Q

How is ovulation induced?

A

Ovulation is induced by the LH surge. Positive feedback effect of very high levels of follicular E2 induces a dramatic increase in hypothalamic GnRH and a huge rise in serum LH concentration

28
Q

What is the cause of follicle rupture?

A

Just before ovulation, the ovulatory ‘stigma’ (a bit of basal membrane) bulges out just prior to rupture, strongly suggesting that this area of the follicle has become weakened and the connective tissue has been broken down

29
Q

What happens after ovulation to corpus luteum and the follicle wall?

A

Formation of the corpus luteum and repair of the damage from ovulation.
In the follicle wall, there is:
- increased blood flow
- increased ingress of white blood cells in the ovarian capillaries
- thinning of connective tissue around the follicle wall
- apoptosis of ovarian surface epithelial (OSE) cells imediately above the stigma

30
Q

How is ovulation and follicular rupture characterised?

A
  • By vasodilatation, increased vascular permeability, tissue remodelling - similar to events involved in acute inflammatory process
  • cytokines, prostglandin and proteases are elevated in the region of the follicular rupture
31
Q

How is inflammation after follicle rupture controlled?

A

Cortisol in follicular fluid rises after LH surge and provides an anti-inflammatory environment so that ovarian damage is limited

32
Q

Why worry about ovarian inflammation?

A
  • 90% of ovarian cancers originate in the ovarian surgace epithelium (OSE)
  • successive bouts of OSE cell inflammation have been shown to induce DNA damage, with the potential to lead to mis-repair of DNA and subsequent malignant changes
  • pregnancy and breast-feeding (fewer ovulations) protect against ovarian cancer
33
Q

What are the final steps of ovulation?

A
  • the oocyte is picked up by the fimbria of the Fallopian tube and transported by ciliary action into the open end of oviduct
  • the oocyte then travels down the Fallopian tube (by ciliary action and peristalsis) to the isthmus (the site of fertilization) where its progress is blocked (unless fertilisation occurs)
  • the oocyte remains viable for about 24 hours