Meiosis Lecture Sep 25 Flashcards

1
Q

At the most basic level, how to mitosis and meiosis differ?

A

Meiosis involves one round of S and then two division: meiosis 1 and meiosis 2. THis results in 4 haploid cells.

Mitosis is an S and one division, resulting in 2 diploid cells.

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2
Q

How do mitosis and meiosis differ in terms of prophase 1?

A

For meiosis Prophae 1, homologous chromosomes will pair up and undergo crossing over/homologous recombination to promote genetic variability

In mitosis, homologous chromosomes do NOT pair up and will align single file during metaphase

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3
Q

What two characteristics of meiosis result in increased genetic variability?

A
  1. random assortment of the homologous chromosomes along the metaphase plate during metaphase 1. It is totally random which chromosome will face which spindle pole.
  2. Homologous recombination - crossing over of homologous chromosomes during prophase 1.
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4
Q

In meiosis, cohesins connect both the homologous chromosomes and the sister chromatids.

How then does the cell manage to have only the homologous chromosomes separate during anaphase 1 and not the sister chromatids?

A

A protein called Sgo complexes with the cohesins between the sister chromatids but not the homologous chromosomes.

The Sgo blocks APC activity against the cohesion between the daughter chromatids, but it isn’t present between the homologs, so APC ubiquinates the cohesins and breaks those down

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5
Q

Where does recombination occur along the homologous chromosomes?

A

at recombination molecules

there are usually about 2-3 per chormosome

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6
Q

what is another name for a homologous chromosome pair?

A

a bivalent

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7
Q

WHat causes nondisjunction?

When does it occur?

A

Nondisjunction results from a failure of chromosomes to separate normally in anaphase.

This can occur in meiosis 1 or 2! (can also occur during mitosis)

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8
Q

What does nondisjunction result in?

A

aneuploidy

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9
Q

What will happen to the number of chroomsomes in the 4 daughter cells after a nondisjunction in Meiosis 1?
After nondiscjuntion in Meiosis 2?

A

In meiosis 1: You’d get 2 daughter cells with n+1 chromosomes and 2 daughter cells with n-1 chromosomes

In meiosis 2: you’d get 2 daughter cells with the appropriate number of chromosomes, 1 daughter cell with n+1 chromosomes and 1 daughter cell with n-1 chromosomes

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10
Q

In what chromosomes do nondisjunctions usually occur?

A

the sex chromosomes

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11
Q

What is the attachment structure connecting the 2 homologous chromosomes together in prophase 1 called?

A

synaptonemal complex

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12
Q

Describe the steps and timing of spermatogenesis.

A
  1. Primordial germs cells develop and migrate to the developing gonads in the 4th week of embryonic development
  2. THe PGCs develop into spermatogonia
  3. The spermatogonia will reproduce via mitosis during fetal development.
  4. Eventually they will arrest after Mitosis and will remain dormant until puberty
  5. At puberty, the spermatogonia are stimulated to resume mitosis and increase in number again (this will continue in the seminiferous tubules of males for the rest of their life)
  6. Subsequently, subsets of spermatogonia (the primary spermatocytes) will enter Meiosis 1 (this continues through the entire life of the male). This forms secondary spermatocytes
  7. The secondary spermatocytes will enter meiosis 2 and become haploid spermatids
  8. Morphological transformation turns spermatids into spermatozoa (mature sperm)
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13
Q

Describes the steps and timin of oogenesis.

A
  1. primordial germ cells migrate to developing gonads at week 4 of development
  2. The PGCs develop into oogonia, which replicate through mitosis to form 7 million oogonia
  3. Between the 3rd and 5th months of fetal development, the oogonia will enter meiosis 1, arresting in prophase 1, becoming primary oocytes.
  4. At birth, a huge number of primary oocytes die off, leaving only about 400,000 - these are all the female will ever have
  5. THe primary oocyte will remain arrested in prophase 1 until puberty, protected within a follicle
  6. At puberty,, just before ovulation, a few primary oocytes will complete meiosis 1, becoming secondary oocytes.
  7. The larger secondary oocyte will enter meiosis 2, but will arrest in metaphse 2 during ovulation.
  8. If the ooctye is fertilized by sperm, it will complete meiosis 2
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14
Q

What enzyme induces the gonial cells to enter meiosis 1?

Why does this not occur in males until puberty when it happens during development in females?

A

Retinoic acid is what induces the gonial cells to enter meiosis 1.

This doesn’t happen until puberty in males because they have a cytochrome that inhibits retinoic acid until its broken down in puberty

Females don’t have thi cytochrome, so the retinoic acid is never inhibited and the oogonia enter meiosis 1 during fetal development

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15
Q

What protein is involved in the primary ooctye arrest in prophase 1 until puberty?

A

high cAMP levels are produced and maintained by the primary occyte and the surrounding follicle cells.

This keeps M Cdk activity low, arresting further progress.

However, at the beginning of puberty, the cAMP levels with drop in a select few follicles in response to the FSH/LH surge in each menstrual cycle.

This relieves the inhibition of M Cdk activity and meiosis re-commences

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16
Q

What proteins causes the arrest of the secondary oocyte in metaphase 2 during ovulation?

A

The FSH/LH surfe induces cytostatic factor (CSF) which inhibits APC

Thus, the ovulated occytes arrest in metaphase 2 and cannot enter anaphase 2 unltess they’re fertilized

Fertilization leads to the inactivation of CSF, allowing meiosis to be completed

17
Q

What are the 4 main steps of fertilization?

A
  1. capacitation
  2. acrosome reaction
  3. sperm-egg fusion and block of polyspermy
  4. first cell cycle
18
Q

What does capacitation entail?

A

As the sperm is in the female reproductive tract (for about 5-6 hours), changes will occur to increase the fertility of the sperm:

You get a cholesterol efflux from plasma membrane

membrane hyperpolarizes

you increase the cytosolic pH

it unsmaks the cell surface receptors that bind the sperm to the egg

Ca2+ and HCO3- enter the sperm and activate a soluble adenylyl cyclase enzyme to increase cAMP, leading to the tyrosine phosphorylation of many proteins

19
Q

What is the basic structure of a sperm?

A

It has a head with the acrosome out from (a lysosomal structure with hydrolytic enzymes)

There is a nucleus filled with very condensed haploid DNA

There is a flagella for motility which has a cable to microtubules in it which come off of a centrosome near the nucleus

Mitochondria are high in number around the microtubules to provide energy for flagella motion

20
Q

What are the layers that surround the egg?

aka, what is the structure of an oocyte?

A

The first barrier is the follicle cells of the ovary.

Just under the follicle cells (so the outside of the oocyte) is the zona pallucidum which has 3 important proteins: ZP1, ZP2, and ZP3.

Beneath that is the egg plasma membrane

Just below the membrane are corticle grandules containing hydrolytic enzymes.

21
Q

How does the sperm enter the egg?

A
  1. The sperm penetrates through the follicle cells by beating ot its flagella
  2. At the zona pellucida, plasma membrane proteins on the sperm specifically bind to ZP-3 in the zona pellucida - the sperm receptor
  3. Binding to ZP3 activates sperm plasma membrane Na+/H+ transporters and Ca++ transporters. This reuslts in an increase in sperm cytoplasmic pH
  4. the increase in pH signals a wave of Ca++ influx.
  5. THe Ca++ influx signals exocytosis of the acrosomal vesicle, liberating its hydrolytic contents

****THIS IS THE ACROSOMAL REACTION****

  1. The hydrolytic enzymes digest the zona pellucida and allow the sperm to contact the egg plasma membrane by exposing specific membrane components involved in sperm-egg binding and fusion
  2. Once they’re in contact, the sperm and egg plasma membranes will bind to each other and fuse (using Izumo and CD9)
  3. Fusion allows sperm phospholipase C to produce IP3 from phosphatidylinositol
  4. IP3 will go to the oocyte ER and trigger a massive release of Ca++ into the oocyte cytoplasm
  5. The Ca++ wave triggers cortical granule exocytosis

11, The contents of the cortical granules modify the zona pelludia and destroy the sperm binding capabilities of ZP3 and harden the zona, preventing polyspermia

****THIS IS THE ZONA REACTION******

22
Q

What triggers the fertilized oocyte to complete meiosis 2?

A

The Ca++ wave stimulates the egg to increase its rate of mRNA and protein synthesis.

It also leads to the destruction of CSF

Since the CSF is no longer around to inhibit APC, the oocyte can enter anaphase 2 and complete meiosis

this produces a haploid pronucleus

23
Q

How do the sperm and egg pronuclei join together?

A

While still separate, both pronuclei (haploid!) will enter S phase of the first cleavage division

While in S phase, the pronuclei will approach each other through the action of microtubules and microfilaments.

The nuclear envelopes fuse

They enter M phase and the condensed replicated chromosomes will mingle on the forming metaphase plate

24
Q

What is the first step if a couple is having a hard time getting pregnant?

A

Semen processing and intrauterine insemination

This is done when the total sperm count falls below 50 million/ejaculate and less than 50% motility

  1. sperm collection
  2. sperm processing (harvest healthy sperm from a pellet using the “swim up” method)
  3. Intrauterine insemination (place collected sperm in the uterus of the female)

This is usually enough to fix subfertility stemming from abnormalities in sperm volume, concntration or mophology and antibody-based infertility

25
Q

If semen processing and intrauterine insemination don’t work, what are some techniques couples could try?

A

assisted reproduction techniques

This involves harvesting both sperm and egg

  1. Gamete IntraFallopian Transfer (GIFT)
  2. In Vitro Fertilization-Embryo Transfer (IVF-ET)
  3. Sub-Zonal Insemination (SUZI)
  4. Intracytoplasmic SPerm Injection (ICSI)
26
Q

How does Gamete Intrafallopian Transfer work?

A

a few eggs and a lot of sperm are placed directly into the fallopian tube, usually about 1.5 cm into the ampulla
via US-guided transvaginal delivery by catheter

27
Q

How does In Vitro Fertilization-EMbryo Transfer work?

A

Eggs and sperm are combined in a petri dish and allowed to undergo fertilization

If fertilization is successful, the embryos are then placed into the fallopian tube or uterus

28
Q

How is ZIFT different from IVF-ET?

A

ZIFT basically does the same thing as IVF-ET, but instead of implanting the embryo, you implant the zygote

29
Q

How does sub-zonal insemination work?

A

in a petri dish, 2-10 sperm are injected with a micropipette directly into the space between the zona pellucida and the oocyte plasma membrane (peri vitelline space).

Fertilization is monitored and the zygotes or embryoes are replaced in the uterus or fallopian tubes

***This is used in cases where sperm are unable to traverse the zona pellucida***

Zonal drilling is similar

30
Q

How does intracytoplasmic sperm injection work?

A

A single sperm is placed into a micropipette and microinjected directly into the egg cytoplasm

Fertilization is monitored and embryo/zygote is implanted into the uterus

The sperm doesn’t have to be motile or even alive!

This is highly effective in severe cases of male factor infertility, but technically demanding

31
Q

What is the success rate for hormonal treatment of anovulatory deficits in females?

A

High - 73% in polycystic ovary syndrome and 95% in weight related amenorrhea

32
Q

What is the success rate of IVF?

A

60% currently, but this may not be straightfoward because clinics select for good candidates

33
Q

What reproduction assistance method is the most common now?

A

Intracytoplasmic Sperm Injection