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Some General
Considerations
In this chapter, we shall consider some topics of interest to the student of embryology that do
not deal with the development of any particular organ as such.
Fourth Week
At the beginning of the fourth week, the embryonic disc undergoes folding, and it becomes
C shaped. Folding of the embryo also leads to the formation of the foregut, the midgut and the
hindgut.
The pharyngeal arches start appearing at the end of the fourth week.
The heart produces a large prominence on the ventral aspect of the embryo. The heart
starts functioning by the end of the fourth week.
At this stage the forebrain is the most cranial and most prominent structure of the embryo.
The upper limbs appear as paddle shaped buds.
The otic pits and the lens placodes become visible.
Fifth Week
Further development of the head and of the face occurs rapidly.
The mesonephric kidney starts forming.
Sixth Week
The upper limbs show further differentiation so that the elbow and digits can be recognised.
The lower limb buds and the external ear start forming.
Further development is seen in the eyes, eyelids and ear.
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Seventh Week
The hand shows formation of digits. Ossification of bones starts in the upper limb.
Eighth Week
The limbs and digits are fully formed. Movements start taking place in the limbs.
Bone formation begins in the lower limbs.
The neck appears between the head and the thorax.
The external genitalia may start showing sex differences.
The tail disappears.
At the end of the embryonic period the embryo can be recognised as human even though
its size (CR length) is only about 30 mm.
age. Various other measurements are also used. For example (with the use of ultrasound) we
can measure the dimensions of some parts of the fetus (e.g.,head, foot length).
The eyes and ears are now in their definitive positions. As a result the fetus becomes more
human.
The process of ossification is seen in all long bones.
Intestinal loops that had herniated out of the abdominal cavity now return into it.
The male and female external genitalia can be visualised using ultrasound imaging.
Urine formation begins.
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The lower limbs reach their final relative length as compared to the rest of the body.
Movements in the limbs are not very strong but can be seen on ultrasound examination.
Maternal Factors
Adequate availability of nutrition in maternal blood and its transfer across the placenta are
essential for normal growth of the fetus. Malnutrition in the mother affects fetal growth and
can possibly cause fetal malformations. As a rule, maternal hormones do not pass through
the placenta and hence they cannot affect fetal growth. However, they can influence the fetus
indirectly by controlling maternal metabolic processes.
Placental Factors
1. Hormones secreted by the placenta can influence the fetus indirectly by influencing
maternal metabolism. For example, somatomammotropin (hCS) secreted by the placenta
has an anti-insulin effect leading to increased plasma levels of glucose and amino acids in
maternal blood. The availability of these to the fetus is, thereby, increased.
2. Placental hormones also have a direct influence on fetal growth. Somatomammotropin
increases fetal growth. Human chorionic gonadotropin (hCG) stimulates growth of the
fetal testis.
Fetal Factors
Fetal growth is influenced by genetic factors. However, genetic factors that determine the
height of the individual operate mainly in postnatal life (through the action of the growth
hormone and of the thyroid hormone). Fetal endocrine glands start functioning near the
middle of intrauterine life. The effects of hormones produced by them may be different from
those seen in postnatal life, the modifications being necessary for requirements of the fetus.
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For example, the fetal adrenal gland starts producing cortisol in the 9th week. In an adult,
cortisol has a catabolic effect. To prevent this, cortisol secreted by the fetus is converted to
cortisone (which does not have this effect).
Growth hormone (produced by the hypophysis cerebri) and thyroid hormones have very
little effect on fetal growth. Infants in whom these hormones are deficient do not show growth
retardation.
However, as discussed earlier, sex hormones produced by developing gonads greatly
influence differentiation of genital organs in both sexes.
the mother may not even be aware of her pregnancy. Therefore she may not take the
necessary precautions.She may keep on consuming harmful products like drugs, alcohol
or cigarettes.
During the fetal period that follows, teratogenic influences become much less severe.
2. The type of malformation produced depends on the exact timing of the teratogenic
influence. Each organ seems to have a critical period during which it is most sensitive to
teratogens.
3. The susceptibility to a teratogen is influenced by genetic factors. A fetus of one genotype
can be much more susceptible to the same teratogen than a fetus of another genotype.
4. Teratogenic agents act by influencing metabolic processes.
5. The dose and duration of exposure to teratogen is also important. High concentration and
long period of exposure to a teratogen is relatively more harmful.
About 80 per cent of all congenital malformations are produced by a combination of genetic
and environmental factors. Of the remaining 20 per cent, about half are caused exclusively by
genetic or chromosomal factors and the remaining half exclusively by environmental factors.
Hereditary Causes
Anomalies may be caused by defects in a specific chromosome or in a specific gene.
Chromosomal defects owe their effects to the absence of certain genes, or presence of
extraneous ones on them. Hence, all hereditary defects are ultimately caused by failure of
the cells to synthesise the right proteins (specially enzymes) at the right time. In producing
an anomaly, the genetic defect may directly affect the organ, or may have an indirect effect.
For example, a genetic defect that leads to agenesis of the testis, may indirectly influence the
developing external genitalia by interfering with the production of hormones necessary for
their development. Similarly, an anomaly of a blood vessel may interfere with the blood supply
of an organ and hence adversely affect its development.
2. Malnutrition
The developing fetus requires all elements of nutrition in adequate quantity for normal
development. In experimental animals, deficiencies of vitamins, minerals (like calcium or
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phosphorus), certain trace elements, and of some amino acids have been shown to cause
anomalies. It is believed that iodine deficiency causes endemic cretinism. However, the extent
to which nutritional deficiencies are responsible for anomalies in humans is controversial.
3. Antigenic Reactions
The body of every animal contains a large number of proteins. The proteins differ not only
from species to species, but even amongst individuals of the same species. The body has the
ability to recognise any protein that is foreign to it. A foreign protein is often called an antigen.
Whenever such a protein enters the body, substances called antibodies are produced and their
function is to destroy the antigen. Remember that a protein normally present in one person
may act as an antigen when introduced into another person, whose body does not contain
it. One such protein present in the blood of most persons is called the Rh-antigen. Persons
having it are Rh-positive and those without it are Rh-negative. It is sometimes possible for an
Rh-negative mother to have an Rh-positive fetus. Some Rh-antigen from the fetus can enter the
mothers blood. If this happens, the mothers body produces antibodies against this antigen.
These antibodies pass back into the fetal blood where they destroy the blood cells containing
the antigen. This breaking up of blood cells is called haemolysis and the disease is called
haemolytic disease of the newborn.
5. Hormones
Administration of synthetic oestrogens or progestins can cause malformations. Progestins
ethisterone and norethisterone can cause masculinization of female genitalia. Fetuses exposed
to diethylstilbestrol (a synthetic oestrogen) in intrauterine life, show increased incidence of
carcinoma of the vagina and cervix in later life. Maternal diabetes can also cause congenital
malformations.
Physical Factors
Physical environmental conditions are less likely to influence mammalian embryos that
grow within the uterus, as compared to those that grow in eggs, or in water. However, the
mammalian embryo is not completely immune to these influences. The greatest danger lies
from radiations of various kinds, including X-rays and radioactivity. These are capable of
producing permanent changes (mutations) in the nature of genes, specially in the germ cells,
and these in turn can lead to the production of congenital anomalies. Some physical factors
that can produce abnormalities are as follows.
1. In experimental animals, hypoxia has been shown to produce anomalies.
2. Abnormal intrauterine environment due to an abnormal site of implantation, due to the
presence of twins, because of an abnormal position of the fetus within the uterus, because
of too much amniotic fluid (hydramnios) or because of too little fluid (oligamnios).
3. Insufficient or excessive availability of oxygen. Too much oxygen leads to a condition
called retrolental fibroplasia.
4. Hyperthermia or increased body temperature is teratogenic. Increase in temperature may
be due to fever secondary to infection, or due to bathing with hot water for long duration.
Hyperthermia leads to mental retardation, cleft lip and cleft palate, limb deficiency, spina
bifida and anencephaly.
Ultrasonography
Ultrasonography is widely used to assess the condition of the developing fetus in utero because
the investigation is cheap, readily available, and has no harmful effects. One can determine
fetal age and size, position of placenta, condition of fetal membranes and the presence of
multiple births. Birth defects can be detected at an early stage of pregnancy.
Amniocentesis
In this procedure a needle is passed through the abdominal wall of the mother and made to
enter the amniotic cavity of the fetus. About 20 ml of amniotic fluid is withdrawn. This procedure
is usually performed between the 15 and 18 weeks of gestation. Amniotic fluid obtained is
used for chemical analysis (alpha fetal protein and acetylcholinesterase). Amniotic fluid also
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contains epithelial cells from the skin of the fetus. These can be used for karyotyping. These
epithelial cells can also be used for determining the sex of the fetus by the simple procedure
of detecting sex chromatin. Such tests are however illegal in India as they often lead to female
feticide.
Fetoscopy
The fetal body may be directly observed for congenital anomalies by using a fiber-optic lighting
instrument. This procedure is usually performed during 17 to 20 weeks of gestation.
MR Imaging
Magnetic resonance imaging of a fetus can be performed to get further information about
conditions that have been detected in ultrasonographic images. MRI is safe and provides high
soft tissue contrast and resolution.
FETAL TREATMENT
In selected cases, treatment of a third trimester fetus is possible with limited success. Such
treatment has been used for fetal anemias, hemolytic disease, fetal cardiac arrhythmia,
thyroid dysfunction and surgical corrections.
Fetal Transfusion
Fetal transfusion is given directly into the umbilical vein by the PUBS procedure.
Fetal Surgery
Surgical correction of some birth defects in the fetus has become possible. In this procedure
the uterus is opened by cesarean section and the fetus is operated upon directly. After repair of
the defect the fetus is placed back into the uterus. Most of the surgeries in utero are performed
after 28th weeks of pregnancy.