Gametogenesis Flashcards
What is meant by a somatic cell?
A cell that contains 46 chromosomes arranged as 23 pairs
- there are 22 pairs of matching chromosomes (autosomes) and 1 pair of sex chromosomes
- these are known as diploid cells
What is a haploid cell?
A gamete (sperm or oocyte) is a haploid cell as it contains only 23 chromosomes
This is half the number of chromosomes as a somatic cell
What type of cell are the only cells in the body not to be a somatic cell?
Gametes are the only cells in the body that are not somatic cells
When does development begin?
Development begins following fertilisation
- this occurs when the male gamete (sperm) unites with the female gamete (oocyte) to form the zygote
What actually is gametogenesis?
When does it occur in relation to fertilisation?
it is the conversion of primordial germ cells into male and female gametes
- it occurs in preparation for fertilisation
- it involves meiosis to reduce the number of chromosomes allowing diploid precursor cells to become haploid gametes
What are the “4 M’s” of gametogenesis?
- Migration - of PGCs to the gametes
- Mitosis - an increase in the number of PGCs
- Meiosis (I & II) - to reduce the chromosomal numbers
- Maturation - of gametes
What cells give rise to gametes?
Where are these formed from and where do they migrate to?
Gametes are derived from primordial germ cells (PGCs)
- they are formed from the epiblast layer of the bilaminar disc during week 2
- they move through the primitive streak during gastrulation to migrate to the wall of the yolk sac
- they remain in the yolk sac for a number of weeks
Where do the PGCs migrate to after residing in the yolk sac?
What process do they undergo whilst migrating?
- during week 4 they migrate from the yolk sac towards the developing gonads
- they pass through the gut tube and across the dorsal mesentery to reach the primitive gonads by the end of week 5
- as they migrate towards the primitive gonads from the yolk sac, they undergo mitosis to form genetically identical cells
What is a teratoma?
How can they form during migration of PGCs?
- a teratoma is a benign (usually) tumour that contains tissue from all 3 germ cell layers
- it often contains skin, hair, cartilage, brain tissue and/or teeth
- they are formed when PGCs are misdirected to extragonadal sites
- this describes areas outside of the genital ridge
- PGCs are pluripotent and have the ability to develop into many different cell types
What are the 2 most common types of foetal teratoma?
Will those affected still have genitals?
- sacrococcygeal is the most common, followed by oropharyngeal
- if someone has a teratoma, the gonads will still develop if there is migration of some PGCs to the genital ridge
- if there are no PGCs reaching the genital ridge then the gonads will not develop
What is mitosis?
What type of cells does it produce?
- the process by which one cell divides to produce 2 genetically identical daughter cells
- each cell receives the complete complement of 46 chromosomes
What are the 4 stages of the cell cycle?
What proportion of this cycle is taken up by mitosis?
G1 phase
- growth phase in preparation for DNA replication
S phase
- replication of DNA to form 2 sister chromatids attached at the centromere
G2 phase
- growth phase in preparation for mitosis
M phase
- mitosis occurs to produce 2 genetically identical daughter cells, each containing 46 chromosomes
- this is a relatively short component of the cell cycle as most of it is spent in interphase
What mnemonic can be used to remember the 4 stages of mitosis?
PMAT
- P - prophase
- M - metaphase
- A - anaphase
- T - telophase
What occurs during prophase?
What does each chromosome consist of at this stage?
- the chromosomes condense and become visible
- the nuclear membrane disintegrates
- each chromosome consists of 2 sister chromatids joined at the centromere
- chromosomes continue to condense, shorten and thicken but chromatids only become distinguishable at prometaphase
What happens during metaphase?
- the chromosomes line up along the equatorial plane of the cell
- each chromosome is attached by its centromere to the centriole via microtubles, forming the mitotic spindle
What happens during anaphase?
- the centromere of each chromosome divides
- the sister chromatids are pulled towards opposite ends of the cell by the spindle (microtubles)
What happens during telophase?
- the chromosomes uncoil and lengthen
- a nuclear membrane forms around the chromosomes at opposite poles of the cell
- the cytoplasm divides (cytokinesis) to form 2 genetically identical daughter cells
What are the main differences in mitotic ability in males and females?
- Mitosis of PGCs continue once they reach the genital ridge
In females:
- there is rapid mitosis of oogonia during months 2-5 of foetal development
- this peaks at around 7 million oogonia
- the majority of oogonia then undergo atresia (degenerate and break down)
- atresia of oogonia continues throughout life until the menopause
In males:
- spermatogonia maintain the ability to divide throughout life
- there is no rapid mitosis during development
What are the 3 key differences between meiosis and mitosis?
In what way are they similar?
- meiosis reduces the number of chromosomes to produce haploid cells (23 single chromosomes)
- meiosis involves 2 successive divisions - meiosis I & II
- meiosis produces daughter cells that are genetically unique
- they are similar in the way that they are both preceeded by the S phase to replicate the DNA of each chromosome prior to division
What is different about the way the chromosomes line up during prophase I?
- S phase occurs so that each of the 46 chromosomes is replicated into sister chromatids
-
homologous chromosomes align themselves in pairs in a process called synapsis
- replicated maternal and paternal homologues line up with each other
- Following synapsis, crosslinking occurs which allows maternal and paternal chromosomes to swap some genetic material
- the point where the crosslinking occurs is called a chiasma
How is genetic variability produced during meiosis I?
How many daughter cells are produced by meiosis?
- crosslinking redistributes genetic material between maternal and paternal homologues
- there is random distribution of homologous chromosomes to the daughter cells as the way the pairs align on the equator during metaphase I is random
- meiosis produces 4 genetically unique haploid daughter cells
What is meant by oogenesis?
the process by which oogonia differentiate into mature oocytes
What happens to PGCs once they reach the gonad of a genetic female?
- PGCs differentiate into oogonia, which then undergo a number of mitotic divisions
- by the end of month 3 they are arranged in clusters surrounded by a layer of flat epithelial cells (follicular cells)
- these are derived from the surface epithelium covering the ovary
How are primary oocytes formed?
- the majority of oogonia continue to divide by mitosis
- some oogonia reside in the prophase stage of meiosis I - these are primary oocytes
- they undergo rapid mitosis until the 5th month of development where the number of germ cells in the ovary reaches 7 million
- following this, the oogonia and primary oocytes begin to undergo atresia
Following atresia of oogonia and primary oocytes, which structures remain?
- all surviving primary oocytes have entered prophase I of meiosis
- they are individually surrounded by a layer of flat follicular epithelial cells to form a primordial follicle
Near the time of birth, what happens to the primary oocytes that remain?
- all primary oocytes have started prophase I of meiosis
- they do not proceed into metaphase, but enter the diplotene stage
- this is a resting stage of prophase that the oocytes will remain in until puberty
How many primary oocytes remain at puberty?
What happens during a menstrual cycle?
- around 40,000 primary oocytes remain at puberty
- with each cycle, a number of follicles begin to develop but usually only one will reach full maturity
- the others will degenerate and become atretic
- this secondary follicle induces a surge in LH, which causes the primary oocyte to complete meiosis I
- there is formation of 2 daughter cells of unequal size - a secondary oocyte and the first polar body (receiving less cytoplasm)
What happens to the secondary oocyte after its formation?
- the cell enters meiosis II but arrests in metaphase II around 3 hours prior to ovulation
meiosis II is only completed if the oocyte is fertilised
- the cell degenerates 24 hours after ovulation if fertilisation does not occur
What is meant by spermatogenesis?
When does this occur?
- this is the process by which spermatogonia are transformed into spermatozoa
- unlike oogenesis (which begins prior to birth), this begins at puberty
- the sperm cells complete meiosis II immediately
What are the 2 different types of chromosomal abnormalities?
chromosomal abnormalities can be numerical or structural
- numerical abnormalities are aneuploidies in which the cell contains an abnormal number of chromosomes
- structural abnormalities can include deletions and fragile sites
in a deletion, small parts of the chromosome are accidentally lost
a fragile site is a region of the chromosome that is susceptible to damage and often DNA loss occurs here
What are the 3 mechanisms by which Down’s syndrome can occur?
What type of chromosomal abnormality is this?
- it is trisomy 21 - a form of aneuploidy as each cell contains an extra chromosome so is not euploid
- 95% cases are due to non-disjunction occuring during M1 or 2
- 4% of cases are due to an unbalanced translocation
- 1% of cases are due to mosaicism (mitotic non-disjunction)
What are the features of Down’s syndrome?
- hypotonia
- small nose with flat nasal bridge
- small mouth with protruding tongue
- eyes that slant upwards and outwards
- flat occiput
- sandal gap (large space between first and second toe)
- broad hands with short fingers
- single transverse palmar crease
- below average weight and length at birth
- 1 in 10 will also have additional difficulties such as ASD or ADHD
Why do people with Down’s syndrome often have a reduction in life expectancy?
Due to the associated complications, such as:
- glue ear
- 50% also have congenital heart defect
- bowel problems (constipation, diarrhoea, coeliac disease, reflux)
- visual impairments
- hypothyroidism
- increased risk of infections
- increased risk of developing dementia at a younger age
What is meant by non-disjunction?
this is the failure of homologous chromosomes to separate during meiosis I
or of sister chromatids to separate in meiosis II or mitosis
this results in daughter cells with an abnormal number of chromosomes - ANEUPLOIDY
What is the result of non-disjunction occurring during meiosis I?
- a pair of homologous chromosomes fails to separate, leading to a dissimilar number of chromosomes in the second set of cells
- this unequal sharing of genetic materal means that all 4 daughter cells have an abnormal chromosome number
- 2 daughter cells will have an extra chromosome (24 or n+1) and 2 will be missing a chromosome (22 or n-1)
- this will result in either a trisomy (if a gamete with 24 chromosomes is fertilised) or a monosomy (if a gamete with 22 chromosomes is fertilised)
What is meant by mosaicism?
mosaicism is non-disjunction that occurs during mitosis
- this results in some daughter cells having an abnormal chromosome number (aneuploid) and some being normal
- the aneuploid cells continue to replicate and make up a subpopulation of cells
How can Down’s syndrome occur due to mosaicism?
Why might someone have a varied expression of this condition?
- Down’s syndrome due to mosaicism can occur:
- in mitosis of a normal zygote
- in mitosis of a trisomy 21 zygote
- there is varied expression of the symptoms of DS as there are 2 different cell populations within the same zygote
- as well as abnormal trisomy 21 cells, there are also normal cells
How can mosaicism in a normal zygote lead to trisomy 21?
- the sperm and oocyte both contain 1 copy of ch21
- fertilisation occurs to produce a normal zygote containing 2 copies of ch21
- mitosis occurs to produce genetically identical cells
- non-disjunction occurs, leading to 1 cell containing 1 copy of ch21 and the other containing 3 copies
- the cell containing 1 copy of ch21 does not survive
- the cell containing 3 copies continues to divide to produce a subset cell population
How can Down’s syndrome result from mosaicism occurring in a trisomy 21 zygote?
- one of the gametes is abnormal and contains 2 copies of ch21
- fertilisation occurs to produce a zygote containing 3 copies of ch21
- non-disjunction occurs to produce a daughter cell with 4 copies of ch21 and the other with 2 copies of ch21
- the cell with 4 copies of ch21 does not survive
- the cell with 2 copies of ch21 continues to divide and make up a normal diploid cell population
- there is also a trisomy 21 cell population from normal mitosis following fertilisation with an abnormal gamete
What is meant by a chromosomal translocation?
What is the difference between an unbalanced and a balanced translocation?
- translocations occur when a chromosome breaks and a piece of one chromosome attaches onto another
Balanced translocation:
- this occurs when there is no loss of genetic material
- breakage and reunion occurs between 2 chromosomes but as no critical genetic material is lost, the individuals are often asymptomatic
Unbalanced translocation:
- this involves loss or duplication of genetic material, resulting in an altered phenotype
How can Down’s syndrome result from a translocation?
it can result from a translocation occurring in a 14-21 carrier
What is meant by a 14-21 carrier?
- in an individual, the long arm of ch21 breaks off and joins onto ch14
- this individual is asymptomatic as the translocation is balanced
- there is no loss of any genetic material
How can Down’s sydrome result from a 14-21 carrier?
- if a parent has a balanced 14-21 translocation, they can pass this on to their offspring
- this results in extra material from ch21
- there is trisomy 21 as there is an extra copy of ch21 attached onto the ch14 that has been inherited from the aysymptomatic parent
What is Turner syndrome?
What is significant about this condition?
There is absence of the second X chromosome, resulting in a 45,X karyotype
It is the only monosomy that is compatible with life
By which 3 mechanisms can Turner’s syndrome occur?
- non-disjunction of the male gamete
- structural abnormalities of the X chromosome
- mosaicism
- 98% of foetuses with this condition are spontaneously aborted
What are the key features of Turner’s syndrome?
- female gender and appearance
- gonadal dysgenesis (failure of the ovaries to form)
- short stature
- webbed neck
- lymphedema of extremities
- broad chest with widely spaced nipples
What is meant by Klinefelter syndrome?
What symptoms does it tend to produce?
there is an extra copy of the X chromosome in males, producing an 47,XXY karyotype
- individuals tend to be asymptomatic but may have some speech / learning difficulties and dystonia of the face
- clinical features are usually detected by amniocentesis and include:
- testicular atrophy
- sterility
- hyalinisation of the seminiferous tubules
- gynaecomastia
Why is there an increased incidence of chromosomal abnormalities with increased maternal age?
- from puberty, 10-30 primary oocytes complete meiosis I each menstrual cycle
- some primary oocytes can be arrested in prophase I for 40 years
- primary oocytes are vulnerable to damage during M1 arrest
The longer an oocyte is arrested in development, the greater chance of chromosomal abnormalities
Why can problems with fertilisation also become more common with increasing maternal age?
- as more oocytes undergo atresia, the follicle pool reduces over time
- in older women, there is a smaller pool of remaining viable follicles
Why does the risk of Down’s syndrome increase with maternal age?
- the rate of non-disjunction increases with age and this is responsible for 80% cases of DS
- this is related to the length of time that the primary oocyte is arrested in the M1 stage of development
Why does only one follicle become mature during each menstrual cycle?
What happens to the others?
- 10-30 primary follicles begin the maturation process each cycle
- while meiosis resumes, the follicular cells surrounding the oocyte also undergo maturation
- only one follicle will mature to a Graafian follicle which can erupt from the ovary
- the other follicles undergo atresia to form polar bodies
How long does spermiogenesis take?
What 4 main changes have to occur during this process?
- the process takes around 74 days
- several changes occur as the spermatid matures into a spermatozoom:
- condensation of the nucleus
- formation of the acrosome
- formation of the neck, middle piece and tail
- shedding of the cytoplasm
Where are developing sperm ejected into?
At what point do they become motile?
- developing sperm are ejected into the semiferous tubercles, which push them along towards the epidydimis
- they do not become motile until maturation is completed within the epididymis
How frequently are abnormal sperm formed?
What are the 4 most common abnormalities?
- unlike oocytes, abnormal sperm occur quite frequently (10%)
- the most common abnormalities are:
- duplicated head or tail
- absent tail
- giant or dwarf sperm
- immotility
How can the presence of abnormal sperm affect fertility?
- the effect of sperm morphology on fertility is not known
- sperm concentration and motility have a correlation with fertility
- subfertility can occur when there is a small portion of abnormal sperm, leading to increased difficulty with conception
