4 - Embyrology Flashcards
Give an overall summary of the process of human embryology during the eight weeks after fertilisation
At what stage of pregnancy is the conceptus referred to as a fetus?
After 8 weeks of development, the conceptus is referred to as a fetus (being recognisable as human)
The later stages of pregnancy are concerned mostly with growth and elaboration of the structures that develop during the first two months.
Summarise the process of ferilisation and early human development
When is embryological development usually considered to start?
Embryological development is usually considered to start with Fertilisation
This leads immediately into Preimplantation Development of the conceptus
Outline pre-implantation development of the human conceptus
Preimplantation development normally occurs within the Fallopian tube (oviduct) over a period of ~6 days, and is characterised by a series of cleavage divisions, which sequentially double the number of cells in the conceptus (2, 4, 8, 16 cells) to produce a ball of undifferentiated cells (the Morula).
The Morula differentiates so that the inner cells differ from those on the outside (Figure 5.2.3).
This then develops into the Blastocyst, a structure that has an outer layer of trophectoderm, an inner cell mass, and a fluid-filled cavity.
Summarise the conversion of an embryo into a morula and blastocyst
Preimplantation development normally occurs within the Fallopian tube (oviduct) over a period of ~6 days, and is characterised by a series of cleavage divisions, which sequentially double the number of cells in the conceptus (2, 4, 8, 16 cells) to produce a ball of undifferentiated cells (the Morula).
The Morula differentiates so that the inner cells differ from those on the outside (Figure 5.2.3).
This then develops into the Blastocyst, a structure that has an outer layer of trophectoderm, an inner cell mass, and a fluid-filled cavity.
The Blastocyst then hatches from the Zona Pellucida (within which it has developed up to this time, about day 6 after fertilisation), and begins to implant in the uterine lining (Session 3.3), a process which is complete about 10 days post-fertilisation. By this time the inner cell mass, which was a group of undifferentiated cells (Figure 5.2.3), has become a bilayer disk, composed of hypoblast and epiblast cells (Figure 5.2.4). This bilayer disk gives rise to all the tissues of the human fetus, through a complex series of changes.
Outline how the bilayer disk of the blastocyst gives rise to all the tissues of the human fetus
This bilayer disk gives rise to all the tissues of the human fetus, through a complex series of changes.
The first of these is gastrulation, which converts the bilayer of hypoblast and epiblast cells into a trilaminar embryo, containing the three layers of Germ Cells (Ectoderm, Mesoderm and Endoderm), occurring during days 14-18 post fertilisation.
Summarise the process of gastrulation
GASTRULATION
This process is summarised in Figure 5.2.5., showing the proliferation (P) of epiblast cells, which then differentiate (D) to form mesoderm cells; these move (M) into the space between the epiblast and hypoblast.
These mesoderm cells are thought to differentiate further to generate the endoderm, which replaces the hypoblast cells which are lost by apoptosis (A).
Formation of the three germ layers is a key stage in embryology, as they are the precursors to all the tissues in the body.
What does the ectoderm give rise to?
ECTODERM
Skin
CNS
What does the mesoderm give rise to?
MESODERM
Muscles
Blood
Skeleton
Heart
Kidney
What does the endoderm give rise to?
ENDODERM
Gut
Lungs
Liver
Why are tissues normally derived from a mixture of germ layer types?
Mesoderm gives rise to musclar and vascular tissues
These are found in many other tissues such as the skin and gut
What is Neurulation?
Before Gastrulation is complete, Neurulation has been initiated
Neurulation is the differentiation of the Ectoderm (Epiblast) to generate the central nervous system (Brain and Spinal cord), under the control of the notocord in the mesoderm of the developing embryo.
The early stages are shown in Figure 5.2.6, with development of the neural plate; this develops two folds, which increase in size until the meet over the neural groove and fuse to form the neural tube (Figure 5.2.7).
This fusion process continues during week 4 of development (Figure 5.2.7), as the central nervous system becomes a sealed tube. Note that the structure of the neural folds is much more complex at the upper (cranial) end of the embryo; brain development has started by this stage.
What process occurs in parallel with neurulation?
In parallel with neurulation, the precursors of other tissues are developing within the embryo, and it is being converted from a flattened structure into a 3-dimensional embryo (Figure 5.2.8).
In addition to structures developing within the embryo during this third week of development (days 14-21), at least two groups of cells are present outside the embryo proper; the primordial germ cells (PGC) in the yolk sac endoderm at the caudal end of the embryo, and the cardiac and vascular progenitors in the primary heart field at the cranial end of the embryo (Sessions 5.3 and 5.4).
Folding of the embryo occurs both laterally, which fuses the ventral midline (chest and abdomen) of the embryo (Figure 5.2.8), and in the anterio-posterior direction, which folds the PGCs into the hind gut, and the developing heart progenitors under the head of the embryo (Figure 5.2.9).
What has developed in the embryo by the end of week 4 of development?
By the end of week 4 of development, the precursors of all internal tissues have been laid down, and many external structures are also developing.
Development during weeks 5-8 involves mostly the elaboration of the tissues generated during the early weeks.
What structures all develop rapidly during the second month of development?
Urogenital, cardiac, facial and lung development all proceed rapidly during the second month of development.
In addition to these structures, limb development occurs over this same time-frame (Figure 5.2.10), as the initial limb buds grow, and the terminal regions are converted to hand or foot plates that in turn develop digits.
Summarise human development during weeks 5-8 post-fertilisation
When does embryonic development technically cease?
Technically, embryonic development ceases after 8 weeks post-fertilisation
This is because the conceptus is now clearly human, and is therefore classified as a fetus – so fetal development would be the correct terminology.
Give an overview of development during the first trimester of pregnancy
Can be summarised as the simple bilayer of cells of the ICM of the blastocyst develops to form all the human structures.
What is the incidence of gross limb/digit defects?
Around 0.5/1000 births
But this can be increased by teratogens such as thalidomide
What is the incidence of less severe hand/digit defects?
Less severe complications, such as polydactylyl (more than 5 digits per hand or foot), are more common
1-10 in 1000 births
Causes are not well understood
Which is more common: polydactylyl or oligodactylyl?
Polydactylyl - more than 5 digits per hand or good
Oligodactylyl - loss of digits
POLYDACTYLYL IS FAR MORE COMMON
Summarise limb development
This is a process that occurs over a number of weeks
What was the effect of thalidomide on limb development?
LIMB DEVELOPMENT AND THALIDOMIDE
Thalidomide was a pharmaceutical drug developed in the early 1950‘s, and marketed as a treatment for morning sickness.
In a majority of countries it was available it was available between approximately 1957-1961, until the link between thalidomide and fetal abnormalities was accepted
Many different abnormalities were reported, affecting many organ systems; in the surviving infants, maldevelopment of the upper limbs was one of the most common outcomes
What is the likely mechanism of action of thalidomide?
THALIDOMIDE: MECHANISM OF ACTION
it seems that it damages developing blood vessels, thus depriving the adjacent cells of nutrients and preventing their proper growth and development.
In humans, it seems that the timing of thalidomide administration (8 weeks of pregnancy onwards, as this is the starting point for severe cases of morning sickness), matches with upper limb development, 6 weeks post-fertilisation.
Also the upper limb blood vessels seem to be particularly sensitive to thalidomide, giving rise to the decreased limb development often observed.
It should be noted that the effects of thalidomide on blood vessels help explain the very wide range of linked complications, as all embryonic tissues depend on normal vascular development for the provision of nutrients.
Define ‘Intersex’
INTERSEX
‘Intersex’ is a preferred terminology to describe sexual development that is neither 100% female or 100% male, and may not match the chromosomes present in the cells of the individuals.
It is estimated to occur in ~0.5/1000 births.
Summarise the main stages of human kidney development
During human development, primitive forms of kidney develop (pronephros and metanephros), which do not contribute to the final kidney that develops from the metaneophros (Figure 5.4.1).
This figure also shows how the kidney changes position during development, and also the relationship between the nephric tissues and the developing gonad.
Note that the ureters, which connect the kidneys to the bladder, extend in length during this process, retaining the kidney-bladder connections; in contrast the kidneys form new connections with the developing arterial system as they move, so that renal arteries break down and re-form during this process.
What typical abnormalities of kidney development can occur?
One kidney may be retained in the pelvis
Retention of an extra artery (or another problem) may obstruct (partly or fully) the ureter, and cause enlargement of the renal pelvis
The kidneys form separately, but may fuse to form a horseshoe kidney and the extra tissue makes it impossible for it to move, so it will remain in the pelvis as shown.
All these abnormalities may compromise kidney function. In an adult, one functional kidney may suffice, but this may not always apply during development.
Summarise early gonadal development
The gonads arise from intermediate mesoderm within the urogenital ridges of the embryo
The genital ducts arise from paired mesonephric and paramesonephric ducts
The mesonephric ducts give rise to MALE genital ducts (Wolffian system)
The paramesonephric ducts give rise to FEMALE genital ducts (Mullerian system)
The gonads and reproductive tracts are indifferent up until 7 weeks of development; differentiation is influenced largely by the presence or absence or SRY (on the Y chromosome)
If SRY+, then development proceeds along the male path
If SRY-, then development proceeds along the female path
Summarise the movement of primordial germ cells during early development
In parallel with the developing reproductive tissues, the primordial germ cells (PGC) are following a separate developmental pathway.
PGC will give rise to the gametes within the gonads, and seem to have a very different development compared with most cells in an embryo.
They originate in the epiblast, but then migrate to the caudal part of the yolk sac (Figure 5.4.5A).
Once the main caudal structures of the embryo proper have developed, the PGC migrate through the hind-gut and dorsal mesentery to the mesonephros and thence to the developing gonads.
By week 7 of development, the embryo has an indifferent reproductive system (Figure 5.4.6), which can differentiate to form either female or male structures.
Describe the indifferent reproductive system prior to its differentiation
Summarise the development of the external genitalia
Succintly summarise the key events in cardiac development
Folding of embryo and heart tube fusion
Heart looping
Septation
Outflow tracts divide
Outline development of the heart
The cardiogenic cells develop in a U (or horseshoe) pattern outside the embryo proper.
These form a pair of heart tubes, which fuse to form a single heart tube by ~21 days post-fertilisation.
This tube is already able to pump blood unidirectionally.
Looping of the heart and septation give rise to the 4-chambered structure of the normal human heart
During this process the vascular connections are maintained, so that the major veins are connected to the atria, and major arteries to the ventricles.
Valves develop, to ensure that blood flows unidirectionally within the heart.
Describe circulation within the fetal heart
The provision of oxygen to the embryo and fetus from the placenta is linked to the main structural difference between the heart in utero, and after delivery.
As little blood flow to the lungs is needed, there is a gap between the atria, the foramen ovale (Figure 5.5.2).
This allows blood returning to the heart (which is relatively high in oxygen) to pass from the right atrium to the left atrium, thence to left ventricle, from where it is pumped through the aorta to the body.
The other major difference is that the main artery from the right ventricle is connected to the aorta by the ductus arteriosus (Figure 5.5.2), diverting blood that would normally go to the lungs into the rest of the arterial system.
Describe what changes occur in the fetal heart at delivery
At birth, the ductus arteriosus and foramen ovale should close, converting the circulation to the ‘figure of 8’ system and allowing oxygenation within the lungs Figure 5.5.3).
What is the Tetralogy of Fallot?
THE TETRALOGY OF FALLOT
One aspect is septal defect between the ventricles which allows deoxygenated blood into the left ventricle, and the stenosis of the pulmonary artery (decreasing blood flow to the lungs).
There are many variants involving the transposition of blood vessels; transposition of the great arteries (Figure 5.5.5) is one of the easier ones to understand. The aorta is connected to the right ventricle, and the pulmonary artery to the left ventricle. This generates two separate blood flows; oxygenated blood is cycled through the left side of the heart via the lungs; de-oxygenated blood through the right side of the heart to the rest of the body.
Before birth, this does not matter, as the foreman ovale and ductus arteriosus allow mixing of the blood flows sufficiently to sustain fetal growth and development.
The closure of these connections after delivery separates the blood flows, so the infant becomes cyanotic (‘blue baby syndrome’). Immediate treatment may involve administering prostaglandins to keep the ductus arteriosusopen, and perhaps opening of a link between the atria.
Definitive treatment would usually involve the switching of the two arteries, to restore the normal blood flows.
The precise pattern of vascular changes can be very variable, so the best treatment can vary considerably between individual patients.
Describe the classical presentation of spina bifida
the classic structure of spina bifida (literally ‘two spines’, showing parallel tissues either side of the spine itself.
In the other images, alternative presentations are shown; the spinal defect is often found towards the lower part of the back, and therefore affects the lower limbs, but the central image shows that spina bifida is not necessarily a single defect, nor is the defect always on the lower back.
When does fusion of the neural tube normally occur during pregnancy?
Formation of the neural tube, the precursor of the central nervous system occurs early in pregnancy, about 3 weeks after fertilisation
Fusion should occur through the neural tube, but in spina bifida this process is not completed.
What is Anencephaly?
ANENCEPHALY
Compromised development of the head and skull is a rarer complication than spina bifida, with an incidence of ~0.2/1000 births.
The general aetiology is thought to be similar to spina bifida, though the result of a lack of closure of the anterior neuropore.
Some studies have suggested that folic acid can also decrease the incidence of anencephaly, although the smaller numbers make it difficult to determine the scale of the benefit.
Outline facial development
FACIAL DEVELOPMENT
The primary structures of the face form on the sides of the head.
This pattern persists until at least 5 weeks post-fertilisation.
The precursors of the nose, cheeks, lips, mouth and chin are also formed during this time period.
As summarised in Figure 5.7.1., these structures then move over a period of about 5 weeks until the reach the expected positions, with the nose centrally placed, and the eyes facing forwards on the face (Figure 5.7.1).
This requires the movement of pre-existing structures (e.g. eyes) through the tissues of the developing face, a process that is not fully understood.
Why are clefts formed during facial development?
While the process may not be understood, the events that occur can be described, and are summarised in Figure 5.7.2.
It seems that repeated formation of clefts in the face, and then filling in of the clefts, leads to sequential loss of tissue from the centre of the face, and the movement of tissues to the correct places.
What is pathological clefting?
One result of this need to form the face from two separated halves is that the process may not function completely, which can give rise to clefts in the lip (usually upper lip, Figure 5.7.3. left) or in the palate.
Clefting in both lip and palate may also be found.
Note that cleft lip is often asymmetric, as only one of the two clefts shown in Figure 5.7.2. does not function correctly, whereas cleft palate is usually symmetric as the halves of the palate do not meet and fuse correctly.
How are cleft structural defects modified?
Surgery
High cell turnover in infants = little to no scarring
Summarise the process of lung development
LUNG DEVELOPMENT
Note that the times used are embryological, not gestational ages: the embryonic period starts at week 0 (not labelled, but implied), and Birth is shown at 38 weeks.
When does the production of surfactant begin?
The production of surfactant begins early in the third trimester of pregnancy (Figure 5.8.1) and gradually increases.
Adequate production of surfactant is necessary for normal lung function at birth.
