Title | Lecture notes, lectures 1-20 - Reproduction, genetics and development |
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Author | brian Mwangi |
Course | Medicine |
Institution | University College London |
Pages | 93 |
File Size | 8.4 MB |
File Type | |
Total Downloads | 272 |
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First Edition Reproduction, Development & Genetics MBBS Y2 Brian Mwangi Reproduction 1 Lorem ipsum dolor rutur amet. Integer id dui sed odio imperd feugiat et nec ipsum. Ut rutrum massa non ligula facilisis in ullamcorper purus dapibus. The first week outer cell layer. This is, i...
Reproduction, Development & Genetics
MBBS Y2
Reproduction
1
Lorem ipsum dolor rutur amet. Integer id dui sed odio imperd feugiat et nec ipsum. Ut rutrum massa non ligula facilisis in ullamcorper purus dapibus.
Ourselves before birth
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The first week
outer cell layer. This is, in fact, where embyronic stem cells are harvested from.
Twins Identical twins can come about in different ways, for example, during cleavage, you can get a splitting of the embryo. This happens in 30% of cases and leads to them having separate membranes. Further on, you can also have a splitting of the inner cell mass, which happens 70% of the time, and you can tell because these have a common membrane. •
ovulation takes place and the oocyte is released
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fertilisation takes place in the ampulla once the egg is taken in, and then flows down the fallopian tube
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cleavage divisions begin to occur, with no increase in egg size, until the morula stage where it resembles a mulberry
•
compaction is where some cells flatten on the outside and other cells condense on the inside. These cells are now committed and have very different lineages •
trophoblast cells line the outside. These go on to produce the placenta
•
cells on the inside become the inner cell mass. These cells are pluripotent, which means they can become any cell except the placenta, which is the
Pre - Implantation Genetic Tests
for couples where it is suspected they will have a child with genetic defects, it is possible to, using IVF techniques, grow an embryo and during, say, the four cell cleavage stage, remove a cell and test it for the genetic defect. Due to regulation, the embryo can easily carry on to term, but if there’s a defect, it is also possible not to return it. Just look at twins!
Tetragenic Chimera This is the phenomenon where two genetically different embryos are fused, and go on to produce a normal, healthy individual.
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Implantation •
the fertilised egg flows down into the uterus, where it receives signalling molecules which cause the trophoblast layer to frantically replicate. •
•
Gastrulation
the replication is so rapid, in fact, that there isn’t even enough time to form a membrane, so the resulting product is a large multinucleate swarm of ‘cell’ called a syncytiotrophoblast.
the syncytiotrophoblast is extremely invasive and destroys extracellular material to make way for the embryo that it is dragging along behind.
•
Following this, the trophoblast is now called the cytotrophoblast because it’s covered in layers of hypoblast, and the inner cell mass has split into the epiblast and the hypoblast.
•
pools begin to form in the syncytiotrophoblast, and the enzymes lysing the extracellular material also dig in to blood vessels, forming lacunae, which are filled with the maternal blood, which is soon going to be exchanged with the child
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starts in week III
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initially, on the embryonic disk, there is the formation of the primitive streak, which is topped by the primitive node
•
cells of the epiblast are attracted therein, and the first lot to crawl over and go in are the first ingression, and once in, displace the hypoblast cells to create the endoderm
A chart showing the potential of different types of embryonic cells. The decidua are parts that are
• •
cells in the epiblast that go in after that form the second ingression, and go on to fill up the rest of the space as the mesoderm
•
cells that ingress through the primitive node become the notochord •
Stem villi •
•
•
the cytotrophoblast and the mesoderm underneath it begin to extend into the syncytiotrophoblast to form the stem villi. the mesoderm then differentiates into vessels which exchange blood with the nearby lacunae that are filled with the mother’s blood and linked to the uterine circulation This is finished by the 21st day
14d
•
mesoderm collects around the notochord •
paraxial - adjacent
•
intermediate
•
lateral plate - most lateral
the notochord releases signals to the ectoderm above it, which then kicks off the formation of the neural plate,, the precursor of the nervous system •
a ridge forms on day 20 which then starts the edges off folding, and thus begins the closing of the neural tube, which starts from the middle and zips up rostrally and caudally
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•
failure for the tube to close properly can cause anencephaly and spina bifida respectively.
Somites
Complexity Of SHH
These are a good example of embryonic induction. They are formed by paraxial meso-
SHH induces the formation of the floor plate and motor neurons in the neural tube, but at the same time, as you’ll see if you look at its effects on somites, it tells them to make the axial skeleton (sclerotome), without a motor neuron in sight.
Some daughters get dots, some get crosses, some get dots and crosses, others nothing at all. One thing’s for sure, cells that have crosses can’t
How does this happen? Simply, the neural tube is ectoderm and somites are mesoderm. Once they’ve committed, they only express particular transcription factors, as the surface
started down that line, they express TFs peculiar to it.
receptors, cascades and all the rest of it are the same as far as the two tissues are concerned.
Generation of complexity The egg doesn’t start off with muscle, rather, cells differentiate to form the different groups of cells found there. cells are committed to a path, for example, into the mesoderm, where they might commit to being somites, and then go on to form dermatomes. Once they’ve
make things that require dots, and so on
Localised determinants •
found in rapidly dividing organisms
•
laid down in the cytoplasm
•
when the cell splits, different daughter cells get different mixes of the determinants depending on where in the cytoplasm the cleavage happened, and so this expresses a particular concoction of TFs, meaning the cell takes a different turn
Embryonic induction •
adjacent cells signal to one another
•
the factor acts at a cell surface receptor, to set off chains of cascades leading to a change in transcription
derm, called so because it is adjacent to the notochord. they form rostrally to caudally, at specific times and have the potential to form a variety of tissue such as dermatome, the connective tissue beneath skin, the myotome that forms every skeletal muscle cell in the body, and finally the sclerotome, which is involved in creating the axial skeleton (minus the sternum) • SHH •
part of the hedgehog family
•
produced from the notochord
•
causes the somites to produce sclerotome and primes other locations to be responsive to other signalling factors
• WNT •
released from the dorsal neural tube
•
induces epaxial myotome, alongside hypaxial myotome formation from somites
• BMP
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•
induces the formation of hypaxial myotome, in conjunction with WNT
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Placentation
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The placenta
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Haemochorial
extravillus cells
• •
the circulations of mother and baby are always separate
remain in the fetal compartment and migrate into the syncytiotrophoblast (losing their membranes etc in the process)
•
these build bridges that anchor the villi to the mother
•
Two parts •
maternal
if they don’t develop properly, you have a thin shelled implantation that just sits on the sur-
•
foetal
face. Associated with growth restriction and pre-eclampsia.
Development Implantation
•
an outer syncytiotrophoblastic layer which is multinucleated and highly invasive. The hormone producing metabolic factory of the placenta. •
•
zygote (fertilised) travels down the fallopian tube and becomes a morula, then a blastocyst with an inner cell mass (embryoblast) and an outer cell layer known as the trophoblast •
•
•
this implants into decidualised (the endometrial epithelia and supporting tissue (stroma) are swollen, filled with blood and secretory of mucus and glycogen) endothelium on day 8, the trophoblast should have split into two distinct layers •
an inner cytotrophoblastic layer which is mononucleated. They are like trophoblastic stem cells and actually give rise to the syncytiotrophoblast •
villus cells
secretes hCG which is a marker of the rate of differentiation of cytotrophoblast into syncytiotrophoblast i.e. doesn’t correlate with the mass of the organ
Chorionic villi •
13-15d
•
primary
terminally differentiated
HCG
•
this molecule, in the first trimester, is used to ascertain pregnancy and as a marker of viability. ectopic pregnancies implant outside of the uterus e.g. fallopian tube and even the ovary. In a healthy pregnancy, hCG levels will double every 24h. in a miscarriage, they rise and fall. in an ectopic pregnancy, the levels rise sub-optimally
•
•
central cytotrophoblastic mass
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peripheral syncytiotrophoblastic surround
secondary •
in a week, get an (extra embryonic) mesodermic core
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villi become branched
•
the syncytiotrophoblastic layer becomes covered in microvilli
tertiary •
you get extra-embryonic blood vessels in the core of a tertiary villus
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•
extremely branched
Basalis •
at the end of the fifth week, you can see them all, but predominantly tertiary
Syncytial Sprouts bits of syncytiotrphoblast split off and are found in the pulmonary tissue. They have a role in triggering and sustaining the immune response, and therefore the immune tolerance of the foetus
the core of the villus
•
•
mesenchymal cells arranged in a network of collagen fibres with cavities often containing macrophages or hofbauer cells. The latter play a role in the filtration of anti-fetal antibodies
•
the collagen fibres begin to condense and better define the fluid filled channels, fully developing by 16w
capsularis
which are life-threatening to the embryo, but after this period of time, the embryo develops enzymes which can cope with radical insult.
the outer cytotrophoblastic shell is the one that separates fetal and maternal circulations •
protects it from high pressure and oxygen
•
maternal blood perfuses into the intervilus spaces after roughly 12w because of the breakdown. Beforehand, blocked out of the intervillus space by cytotrophoblastic plugs. This was shown because oxygen levels were initially very low, sealed by the cytotrophoblast shell, because highly oxygenated blood contains free radicals
•
•
covered in decidua basalis •
large, compact cells, abundant in glycogen and lipids
good for their increase in surface area •
Chorion fondrosum/chorion laeve •
villi now cover most of the chorion
•
the villi at the embryonic pole go on to make the chorion frondosum (bushy chorion)
•
this, alongside the decidua basalis is the only bit participating in exchange, and therefore, is termed the placenta
the villi at the abembryonic pole (the opposite pole to the implanting pole), at the same time, begin to degenerate and form the chorion laeve (smooth chorion)
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•
covered in decidua capsularis •
as the amniotic cavity expands into the chorionic cavity, this gets stretched and thinner, until it contacts the uterine wall (decidua parietalis - related to the organ/uterus) and they fuse and close off the uterine lumen forming the amniotic membrane, this is the one that bursts during labor
so at this point, we’re left with villus trees which are bathed in maternal blood that pools in lacunae formed in the syncytiotrophoblast. trophoblastic invasion (extravillus) •
invasion of spiral arteries by extravillous trophoblast •
•
destroys the media of the uterine arteries and replaces them with fibrinoid material, turning them from thick walled vessels into flaccid, high capcity uteroplacental vessels •
can passively dilate to accommodate increases in maternal bloodflow
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the cytotrophoblasts change their adhesion receptors to mimic those they’re replacing
this is necessary because arteries produce jets not lakes. the foetal circulation needs to be slower to maximise exchange time. therefore, breaking down the muscular wals reduces the pressure. as this happens, the cells switch phenotype to mimic the cells they’re invading, and in cases of preeclampsia, this mechanism doesn’t work.
•
therefore, it is an allograft (same species) and would require immunological tolerance otherwise rejection would occur
•
mechanisms •
villous trophoblast doesn’t express MHC antigens
•
the extravillous trophoblasts have HLA-G which is protective
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the decidual tissue around it has also been shown to be immuosuppressive
Pre-eclampsia in this condition, there is an inadequate infiltration of trophoblasts into the spiral arteries (limited to intradecidual) leading to an insufficient blood supply to the foetus. Eclampsia, associated with HBP, proteinurea, is fitting of the mother. Preeclampsia preceeds this by many weeks.
Cotyledons these are septae formed by the decidua which infiltrate the chorion but don’t make it all the way through to the chorionic cavity. The cytotrophoblasts fail to switch their adhesion phenotype.
happens in two stages
Placenta as a graft or tumour? •
intradecidual
•
intramyometrial
•
the placenta would contain paternal antigens
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pelvic viscera
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Pelvic structures revision •
the pelvic inlet and the pelvic brim are the same thing and mark the entrance into the true pelvis •
•
•
•
this bulk of muscle makes up the majority of the pelvic diaphragm (=pelvic floor)
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the main bulk originates from the pelvic walls and progresses medially and posteriorly, joining up in the midline
this is more circular in women than men
muscles •
•
•
there’s a division anteriorly known as the urogenital hiatus that admits structures into the perineal cavity
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pubococcygeus
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puborectalis
obturator internus •
originates from the deep surface of the obturator foramen
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leaves via the inferior sciatic foramen after a sharp turn and inserts into the greater trochanter
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innervated by nerve to obturator internus
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covered by a fascical thickening known as the arcus tendineus on the surface of which lies the pudendal canal internal pudendal vessels
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attached anteriorly to pubic arch
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pudendal nerve
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free posterior membrane
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attached superiorly to the urogenital hiatus
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both sexes have a urethral hiatus and women additionally have a vaginal hiatus
originates from the sacrum
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inserts into the greater trochanter
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innervated by direct branches of the lumbosacral plexus, L5, S1, S2
•
skeletal muscle sphincter
• •
levator ani •
the muscle in the bladder walls is called the detrusor muscle
perineal membrane/deep perineal pouch
•
•
•
iliococcygeus
•
piriformis
normally lies behind the pubis when empty, and when full, swells and rises above it. However, it is always anterior to peritoneum, never behind it.
this muscle is important in the maintenance of fecal continence, as it acts like a sling on the rectum, pinching it to occlude the lumen and relaxing when its time to evacuate
•
•
•
the perineal body is a thick bit of connective tissue that serves as an attachment site for many muscles of the pelvic floor
bladder
•
the urachus is like the front horn of the bladder, it used to connect the bladder to the umbilical cord but is now called the medial umbilical fold.
ureters •
they come down from the kidneys and into the pelvis, crossing the internal iliac arteries as they do
•
enter at the top of the trigone (a triangle formed by the ureters and the urethra) behind the bladder. At the point of entry, the vas deferens from the testicles hooks over
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•
in females, the uterine artery runs on top of the ureter as they’re both beneath the broad ligament. It’s important for surgeries of that area
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Male viscera •
Urethra the bladder pretty much sits on top of the prostate gland in men •
•
Note: in the place of the rectouterine pouch girls have, e have a rectovesical pouch, between the rectum and the base of the bladder •
preprostatic • •
•
surrounded by prostate
•
the membrane goes into a longitudinal fold called the urethral crest which then expands into the seminal colliculus
membranous •
its called this as it makes its way through the deep perineal pouch
•
here it’s surrounded by the external urethral sphincter (skeletal)
spongy called this as it makes its way through erectile tissue, ends at the tip of the penis in a navicular fossa.
•
they develop in the posterior abdominal wall, descending at birth, and so drag services with them, including lymph, so they don’t drain into inguinal nodes, rather into the pre-aortic, lateral aortic and lumbar nodes.
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their effluent drains into the vas deferens which travels into the body from the scrotum through the spermatic cord
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the testes themselves are riddled with seminiforous tubes which are really tortuous. These then become straight tubules, which collect in the rete testes. From here, they enter into the intensely coiled single tube, the epididymis (head)...