Embryology Flashcards
What is the working/scientific defintion of sex?
Blending genetic characteristics of two individuals of the nth generation to create the (n+1)th generation
What are the advantages and disadvantages of having sex (biological perspective)?
Advantages
1. Each individual has a new mix of genes that give it immunity to pathogens (the Red Queen syndrome) - pathogens evolving to escape our immune system, and so we need to mix our gene sets such that stay on top of the ‘arms race’
2. Each individual has a new mix of genes that determine its environmental interactions
Disadvantages
1. You need to find a partner/mate
2. Dilution of a ‘perfect’ set of genes (if your genes are perfect’) - as you’ll be mixing your genetic information with someone elses
How do the gametes of the two sexes differ?
Male - many small gametes (spermatozoa); provides nurture behaviourally or not at all - low energy intensive/investment needed
Female - many small gametes (spermatozoa); provides nurture behaviourally or not at all - more energy intensive/higher level of investment
Partly explains why females are more ‘picky’ when choosing mates, as conceiving a baby is much more energy demanding/intensive.
Difference between germ line and somatic cells?
Germ line - cells that give rise to gametes (early in development these cell’s are seperated/set aside)
Somatic cells - the rest of the body/anything thats not a germ line cell.
Name the different anatomical features of the testes.
What are these structures in the testes called?
Testes formed from tubular structures - Seminiferous tubules
Between tubules – connective tissue - stroma
When looking at the epithelium of the seminiferous tubules, what types of cell’s do we see? What are their functions?
Observe a gradient of maturing sperm cells from the outside the tube to the inside.
Outside
1. Myoid Cells - smooth muscles cells
2. Spermatogonia - stem cells of the whole system – normal diploid cells – self-renewal and potency to differentiate into spermatocytes
3. Spermatocytes - primary (2n - arises from stem cell division) followed by secondary (1n - arises from primary spermatocyte division
4. Spermatid - haploid gametes arising from secondary spermatocyte division (immature cell)
5. Spermatozoa - sperm cells (mature cell)
Note - in between the developing sperm cells you have sertoli cells - nurse/support mates for differentiating sperms cells - imortant as sperm cells remove as much metabolic function as possible – bare basic, hence requires support
What are the different stages of spermatogenesis?
- Proliferation of germ line stem cells by mitosis
- Reduction to haploid state by meiosis
- Differentiation into mature spermatozoa.
When does spermatogenesis begin?
- Begins at puberty
- Produces (at your age) about 10,000 sperm per second!
- Typically about 10^8 sperm / ml of semen.
(<2x10^7 / ml classified as subfertility)
Outline the steps that take place during meiotic divisions to create male sperm cells.
- Multiplication phase - stem cells undergo assymetric mitotic divisions - basal end of tubule
- Growth phase - Primary spermatocyte and first meiotic division to produce secondary spermatocytes
- Maturation phase - second meiotic division to produce spermatids
- Spermiogenesis - maturation of immature spermatids into spermatozoa - apical end of tubule
Interesting fact - Daughters of spermatogonium division are cross-linked with cytoplasmic bridges to share metabolism.
Outline the hormonal inputs that control spermatogenesis?
- Hypothalamus secretes Gonadotropin-releasing hormone (GnRH)
- Stimulates anterior pituatary gland to release FSH and LH
- Actions of FSH and LH on testes
a) FSH stimulates sertoli cells to stimulate spermatogenesis and produce inhibin
b) LH stimulates Leydig cells to produce testosterone and dihydrotestosterone - which acts locally to stimulate sertoli cells - Negative feedback
a) Inhibin - inhibits FSH release from anterior pituatary and GnRH from hypothalamus
b) Testosterone - inhibits LH release from anterior pituatary and GnRH from hypothalamus
What are the most significant events that take place during sperm maturation?
Theme – removal of the majority of material/metabolic acitivty - removed via cytoplasmic droplet
1. Nucleus and mitochondria remain - mitochondria organising into sheath
2. Vesicles/golgi fuse to form acrosomal cap – important for fertilization
What are the most significant events that take place during sperm maturation?
Theme – removal of the majority of material/metabolic acitivty - removed via cytoplasmic droplet
1. Nucleus and mitochondria remain - mitochondria organising into sheath
2. Vesicles/golgi fuse to form acrosomal cap – important for fertilization
What happens when sperm come into contact with our own immune system?
Most of the learning of self and non-self takes place during the fetal stages of development.
However, given that sperm production starts later in life – sperm located in the ‘wrong’ location, gives rise to an immunological response
Example - In Mumps we can observe immune cells invading the tubules – leads to inflammation and damage – possibility of infertility.
This is why there are tight junctions in the basal compartment of the seminiferous tubules in order to prevent the movement of fluid.
What prefix is used to indicate the testes?
Orch- = prefix for testis (Gk.)
eg orchitis, orchidectomy, cryporchidism etc
Where do sperm ‘learn’ the ability to swim?
Sperm are shed and flow to the epididymis - note at this point the sperm don’t swim but rather are moved passively via smooth muscle contractions
The epididymis the sperm encounter altered seminal fluid - these epididymal secretions (glycoproteins etc) activate sperm and make them capable of swimming
Are irregularly shaped sperm thought to be defective?
Irregular sperm – not a defect per se – studies from mice – irregular sperm can form blood clots – blocks movement of sperm from other competing mates
Do females have germ line stem cells? If no, what are the implications of this?
UNLIKE men, adult women have no germ line stem cells
Note - they may have oogonial stem cells, but for some reason they do not do anything, so functionally there are no relevant germ-line stem cells.
Consequences…
1. During foetal life - mitosis bulks up the number of germ line cells which then differentiate via meiosis into oocytes (partially)
2. 12-50 years of age - most oocytes remain ‘frozen/paused’ while each month a set of follicles complete meiosis, with one being released (menarche to menopause)
Rate of female gamete production – 13/yr
Outline the steps that take a primordial follicle to being released each month.
- Primordial follicle - arrested in meiosis I - follicles are supported by granulosa cells
- Starting in puberty, some primodrial follicles (~50) are stimulated and re-enter the cell cycle to finish off meiosis I
- Primary follicle - During this phase (about 8.5 days), oocyte grows and synthesises rRNA and mRNA. It does not progress further through meiosis.
- Ripening follicle - During this phase (10 days), the oocyte synthesises a glycoprotein zona pellucida, and granulosa cells multiply.
- Granlulosa cells secrete follicular fluid that form the fluid-filled “antrum” - around the follicle you find thecal cells – form shell around oocyte
- Critical stage of the cycle the developing follicle receives a surge of LH from the pituitary gland - stimulates thecal cells to release androgens which then stimulate granulosa cells to produce estrogen.
- The follicle that receives the LH surge at the correct time matures to form a Graafian follicle - the rest die.
- Antral stage - follicle maturation - enters and is arrested in meiosis II and release of polar body.
- Termination of meiosis II of the mature follicle only takes place upon fertilisation
What is the name of the structure left behind following follicle release?
The remains of the ruptured follicle become the corpus luteum.
The Corpus luteum produces hormones (progesterone, oestrogen) that prepares the lining of the uterus to receive an embryo
Unless the woman is pregnant, the CL dies after a week or so – requires signals form embryo
What are the hormonal ouputs from the follicles at different stages?
What are the hormonal inputs to the follicles during menstrual cycle?
How can oogenesis be stimulated artificially?
- Exogenous FSH
- Drugs that block oestrogen detection and thus drive higher production of endogenous FSH - oestrogen drives negative feedback (occurs during the early follicular phase)
What is capacitation? Why is it important for fertilisation?
Capacitation - Process by which glycoprotein and sterol coat, which is acquired in epididymis, is removed by proteases in the uterine/ cervical fluid.
This causes the cell membrane to become more permeable to calcium ions - These (indirectly, via cAMP) activate strong tail lashing and make the acrosome reaction possible later.
Hence… Capacitation is required for fertilisation
What region in the fallopian tube does fertilisation normally take place?
Takes place in the ampulla (closer to the fimbriae) - Embryo needs to start development prior to arriving in the uterus
Kool fact - Specialized cells present in the lower tract of the oviduct – trap sperm – release after ovulation - make it such that sex and ovulation don’t need to be co-occur at the same moment.
What is the acrosome reaction?
When sperm meet the Zona Pellucida of the egg, they undergo an Acrosome Reaction - lock and key type mechanism
- Acrosome membrane and plasma membrane fuse at many points
- Acrosomal contents spill out (e.g. enzymes) and can digest the zona pellucida
Following sperm and egg fusion, how does the oocyte ensure that no other sperm fuse?
Quickest sperm fuses with oocyte membrane - – allows for movement of nuclei into the oocyte (note that the sperm mitochondria die off)
Fusion causes….
1. Waves of calcium to flow into the oocyte
2. This changes the polarization of the membrane and blocks the entrance of another sperm cell
3. Calcium influx also results in the release of cortical granules – these alter the ZP and make it impenetrable by sperm - block polyspermy
Note - Calcium influx also causes meiosis of the oocyte to resume and complete
After sperm fusion and Ca2+ influx, what happens next?
Chromosomes decondense and form the male and female pronuclei - membranes of pronuclei dissolve, allowing for the fusion of genetic material
Note - at this point we also ge the release of a polar bodies (multiple?)
What are the typical reasons why we need assisted fertilisation?
Female
Blocked/absent oviducts - pelvic inflammatory disease, Chlamydia or Gonorrhoea often damage oviducts, congenital absence, endometriosis of earlier elective tubal ligation.
Female Age
Male
Blocked vasa deferentia/ eferentia
Impotence - erectile dysfunction
Low male fertility
Why does female fertility decrease with age?
Fertility drops from the 30s
Oocyte age is the determining factor – as the presence of young donor egg still allow for pregnancy to occur at older age
What are intra-cytoplasmic sperm injections (ICSI)?
Sometimes sperms don’t fertilize – requires assistance
ICSI is a technique used to inject nucleus of the sperm into the oocyte – more risks + incidence of abnormalities are higher
How are genes different to a engineering blueprint?
Outline the early different stages of embryo development (fallopian tube).
- Cleavage division – divisions without growth – point: bulk up cell numbers
- Activation of the embryonic genome - At the 4 cell stage – mRNA synthesis from embryo’s own DNA begins. Maternal mRNA is destroyed at an increasing rate.
- First differentiation event of cells based on location in the embryo - e.g. in the Morula (32-60 cells) - cells on the inside have contact all round. Whereas, cells on the outside have a free surface. This is the first difference, and the embryo uses it.
- Formation of different cell types/layers
a) Cells located on the outside – differentiate to form trophoblasts - forms an epithelium called the trophectoderm - functions to pump fluid – forms blastocyst - these cells will ultimately form the placenta.
b) Cells located on the inside - inner cell mass makes the body itself, plus some extra-embryonic membranes - Trophoblasts produce HCG – signals to maintain the corpus luteum – signals to the body that pregnancy has taken place – maintains thickness of uterine lining.
- Blastocyst ‘hatches’ through Zona Pellucida;
- Embryo journeys down fallopian tube into the uterus.
What happens during blastocyst implantation?
Implantation – the trophoblast of the hatched blastocyst invades the uterine epithelium
Starts the formation of the placenta (mainly formed by the baby/embryo)
Epithelium will also react to form the mother’s part of the placenta
On this picture of an embryo, what are the arrows pointing to?
How does differentiation of cells in the embryo begin?
Based on the different positioning and exposure (what they are in contact with) of the cells - the cells of the inner cell mass are able to differentiate - difference in signalling
Hypoblast - Cells located on the in the inner cell mass that exposed to the fluid filled cavity differentiate into hypoblasts and migrate along the sides of the internal cavity
Epiblasts - Cells located inside the cell mass are solely exposed to the other cells, and thus differentiate into epiblasts
Final product - two disticnt cell layers - epiblasts and hypoblasts - disc shape structure is surrounded by two fluid cavities - Yolk sac and amniotic cavity.
What happen when you have two babies sharing the same placenta (monozygotic twinning)?
Danger of foetal transfusion syndrome (‘twin-to-twin transfusion syndrome)
One fetus consumes more of the blood supply - result is that one of the fetuses grows in starving conditions – adult presents with a group of symptoms – barker syndrome
Note - Correction of blood supply via surgery is possible.
Outline the principle/idea by which an embryo converts it initial radial symmtery (2 axes) into 3 axes?
Principle - create polarity on the the 2 axes structure
How is this done?
Central hypoblast cells start producing Hex - these cells migrate to one pole, in turn setting up a Hex gradient (high one side and low the
other)
Hex expressing cells also express inhibiting proteins that block epiblasts cells in the vinicity from transforming into ‘tail’ cells of the primitive streak. However, this inhibition is limited at the opposite pole, as a result those cells are able to differentiate into ‘tail’ cells
As a result, we get polarity in our structure - with the head and tail at opposite ends.
What is the third way, very rare, form of forming monozygotic twins?
Rare form of forming monozygotic twins - formation of two primitive streaks - result of hex cells not congregating together - two distinct sites expressing hex - formation of two heads and tails.
Embryos share everything + no barrier between the two twins
How are cojoined twins formed?
Partial axis duplications
Two head organizing areas still joing with one tail site
Outline the process by which gastrulation takes occurs.
- Cells in the epiblast layer migrate down into the space between the epiblast and hypoblast - these cells form the mesoderm - largely form the connective tissue of the body
- Some of these epiblast cells join the hypoblast layer, moving the hypoblast cells laterally - this layer of cells is called the endoderm (forms the inner surface of the body)
- The top layer becomes the ectoderm, which develops to form the epithelial surface and neural tissue.
Three layers in order…
1. Ectoderm
2. Mesoderm
3. Endoderm
Which germ layer gives rise to gastrointestinal tract?
Cells derived from the endoderm eventually form many of the internal linings of the body, including the lining of most of the gastrointestinal tract, the lungs, the liver, the pancreas and other glands that open into the gastrointestinal tract, and certain other organs
Image shows how a flat disc-shaped layer of cells lengthing and stretch out to form the internal lining/tube.
Apart from the GI tract, what other ‘tube’ has to be developed in the body?
There are actually two tubes…
a) One open - the gut
b) One closed - the central nervous system
The CNS derives from the ectoderm
Outline the process by which the neural tube is formed?
Ectoderm – cell signaling drives changes in cell shaped, which when pushed/moved due to surrounding cell proliferation results in the formation of a ‘valley’.
Eventually the tube dissociates and is cleaved off from the ectoderm to form the neural tube
Start of the nervous system formation
What are two conditions that are caused by the failure of the neural tube closure? What is the main cause of these conditions?
Spina bifida - one of the most common fetal abnormalities
Anencephaly - no brain – dorsal end of the neuroectoderm does not close - consequence is that the dorsal end does not form, which is central to brain development. Hence, the brain morphogenesis is significantly impaired.
Failure to ‘zip up’ the neuroectoderm
Mainly environmental driver (not only genetics) - Maternal diet requires folic acid – neural tube closure happens before mothers are aware of their pregnancy – highlights the importance of healthy diets prior to pregnancy
What is another example of tissues failling to close in the mouth?
Orofacial cleft: also called ‘cleft lip and ‘cleft palate’
Another place that needs to be ‘sealed up’ is the secondary palate: this often fails.
But this can be treated by surgery
What is another example of tissues not closing properly in the urogenital region?
Hypospadias - 1/250 male births (most are mild forms)
A birth defect in boys in which the opening of the urethra is not located at the tip of the penis - urethra opening normally has to migrate up to the top of the penis - closing zip mechanism
Is the human body proportionate?
Yes, these proportions were described by Da Vinci in his depiction of the Vitruvian man
Note - that proportionatlity also exists internally
It is the role of human development to ensure that all body organs and tissues develop in proportion.
What hormone is responsible, in part, for our bodies growth and development?
Growth hormone produced by the pituatary gland - discovered in patients with a pituatary adenoma resulting in gigantism
Post natally, GH either…
a) acts directly on muscle tissue
b) acts indirectly by stimulating the releases of IGF-1 and IGF-2 (mainly from the liver)
Note - double knockout mice for GH can not survive
If one side of the body’s growth is inhibited, e.g. leg, what mechanism ensures, once inhibition is released, that the leg is able to catch up to the contralateral side?
To understand the mechanism, we first need to understand how internal signalling drives bone growth.
Firstly, dying cells at the growth plate relase CNP, which stimulates younger cells to proliferate and mature.
These younger cells also send signals to the sheath of bone (indian hedgehog), which in turn drives PTHrP release, which tells stem cells to proliferate and differentiate.
Hence, understanding this we can see how in a underdeveloped bone the distance that Indian hedgehog and PTHrP need to travel are reduced, meaning that they will be able to illicit a stronger stimulus - allowing for the bone to catch up in growth
How did thalidomide cause limb abnromalities?
Thalidomide – used to control morning sickness
However, thalidomide inhibits blood vessel growth – thus interfering with limb growth
Now it is used to treat cancer – but not prescribed to pregnant women/women of child bearing age
Environmental cause of a non-vitruvian body
How does the correct amount of skin develop?
Human skin responds to mechanical forces (excessive stretch - stretch receptors) - in turn driving skin growth
Where in the body do the gonads develop?
Your gonads developed in the trunk of your body, about half way between shoulder and pelvis (whatever sex you are) - in the genital ridge
Outline what happens to germline cells during gastrulation?
The germ line cells are derived from epiblast cells that were removed from the body around the time of gastrulation.
Therefore the germ line cells end up outside the body, in the yolk sac. Hence, they need to return to the body later during the development.
Outline how the germ line cells migrate back into body during development.
Primordial germ cells use the gut and its mesentery as a way to invade the body
Mesentery - the sheet-like connection between gut and the rest of the body
When they reach the level of the developing gonads, they move up the mesentery and then move across to enter the gonads themselves.
Around this time, the gonad has to make a decision about whether to develop into a testis or an ovary - XX or XY
Do other tissues in the body respond to the SRY gene?
In eutherian (placental) mammals, the rest of the body pays no attention at all to whether it has a Y chromsome.
It has to take its cues from the testis
The testis communicates with the rest of the body by excreting androgenic hormones - testosterone and anti-Mullerian hormone
What are some external phenotypes that differ between males and females?
Externally obvious differences in:
1. Average height & mass
2. Body shape
3. Development of external genitalia
4. Development of mammary glands
5. Body hair pattern (extent varies with race)
