DEVELOPMENT

Yesterday we had reached the point where we had fertilized the egg. Now we have the
first cell of the next human. This happens in the fallopian tube, and the reason why it has to
happen there is because it is about an eight day trip down the fallopian tube, and you know that
the egg only lives for about 24 hours, so the only place you could possibly get fertilized is in the
fallopian tube. But the cell does not just wander down the fallopian tube and get into the uterus
and start developingdevelopment starts immediately. As soon as the zygote is formed, the
zygote begins dividing mitotically, and that process of mitotic division is very rapid, so it is
called cleavage. The process of mitotic division is cleavage. Remember, when the egg got
fertilized, the vitelline membrane became very hard to prevent sperm from entering, but there is
a functional consequence of that: if that outer membrane is really hard, and the zygote is inside
of that membrane, it cannot get any bigger. So initially, during development, you are just making
more cells, and the cells are progressively getting smaller as you produce more of them, and all
of that is happening inside of the vitelline membrane.
Remember when we talked about deuterostome vs protostome, one of the characteristics
of being a deuterostome was having indeterminate cleavage. Because we have indeterminate
cleavage, the first two rounds of mitosis result in the production of four cells, each of them with
the capacity to form a complete human. It is during the third cleavage, when you go from 4 to 8
cells, that the cells then become more specialized and lose their ability to code for all human
properties. After the four cell stage, each cell acquires a more limited fate in the future organism.
So the cells divide as the conceptus is migrating down the fallopian tube (conceptus is a general
term that describes any point in development). The preembryo is anything prior to implantation;
when you were formed, your preembryonic development occurred while you were migrating

down the fallopian tube. When you got into the uterus, you implanted in the endometrium, and
once you were implanted in the endometrial wall, you became an embryo, and you were an
embryo as long as the endometrium provided your nutrients and oxygen. During the time you
were embryo, you were also forming what is called a placenta, which was derived from your
tissue. Once you had a placenta, you then used your placenta to acquire oxygen and nutrients
from your mothers circulatory system, you became a fetus. You are no longer a conceptus once
you born, you are a neonate.
So development is occurring as the zygote is migrating down the fallopian tube, then
when it gets to the point where it is in the isthmus, which is the boundary between the fallopian
tube and the uterus, it is developed to the point where it has two specialized cellular regions.
One region is called the trophoblast, and the other region is called the embryonic disc.
Collectively, this whole thing is called the blastocyst. At this point, if I were to look at it in cross
section, what I would see is a single layer of cells organized in a tubular structure, and then you
would see another collection of cells which is the trophoblast. The trophoblast is almost like a
parasite, it is ultimately going to furrow into the endometrium, killing all the cells as it goes
along, creating a puddle of fluid, and because the embryonic disc is attached to it, it will bring
the embryonic disc into the endometrial wall, and the endometrium will grow over the hole, and
now the blastocyst is burrowed into the endometrium. Overtime, the trophoblast continues to
break down surrounding endometrium, releasing the nutrients and oxygen in those cells that get
absorbed by the embryonic disc. At this point we have about 100 cells, eight days after
fertilization, it has burst out of the vitelline membrane, and now the trophoblast burrows into the
endometrium and the embryonic disc, which is attached to the trophoblast, follows, it gets walled
off, and that is implantation.

Now embryonic development begins. Right now you only have one layer of tissue, as it
has not specialized, you have not undergone blastulation, gastulation, or neurulation. You will
end up with three tissue types: ectoderm, mesoderm, and endoderm. The ectoderm will be your
outermost layer and will give rise to your outer body surface and nervous system; the endoderm
will give rise to all the endothelia, the inner lining of all your organs; the mesoderm will populate
everything in between, giving rise to things like muscles and bones.
You might remember when we were talking about the clydoic egg, or the amniotic egg,
we said there were layers, the corian, the amnian, the alintose, and the yolk sag, and you have
those same layers, but you are not inside of a closed shell that prevents desiccation, you are
inside of the uterus. You have what are called extraembryonic membranes. You are surrounded
by an amnion, and the amnion creates a fluid filled world, which is the amniotic fluid.
Remember with the clydoic egg, we had a sac that held all of the waste products from the
nitrogenous waste, that was the alentose; you do not have that sac hanging off you, you simply
create a mechanical connection between your circulatory system and the placenta, and the
placenta is connected to the maternal circulatory system, so instead of having a little sac holding
all your waste, you simply connect yourself via the placenta to your mothers circulatory system,
so your aletose becomes your umbilical cord, and the umbilical cord is ultimately attached to the
placenta, which is derived from your trophoblast; so your trophoblast, once it burrows into the
wall of the endometrium, begins differentiating and becoming your placenta. Then all of these
membranes are covered by a very durable outer membrane called the corion for protection.
Remember, the last thing inside a clydoic egg was the yolk sac that held all the nutrients; you do
not need those nutrients because your mother has nutrients in her bloodstream, so you just take
hers, but you still have a yolk sac that does other things unrelated to providing nutrients.

Another thing we need to talk about embryonic and fetal life is the functioning of the
cardiovascular system. You were 18 days when your heart first started beating, because the role
of the heart is to pump oxygen and nutrients to the cells of the body when they are too far away
from their source, so by 18 days you were too big so your heart developed and you sent your
blood vessels out, and invaded the endometrium. When you saw the embryological development
in the chick, the veins went out and invaded the yolk. Remember we said, when we were
talking about the heart itself, we said you really had two functionally separate hearts, the right
side took blood coming back from the body and that then sent it to the lungs, then the blood
came back from the lungs to the left side which then pumped it to the body, and then it was
returned back to the right side. In the developing embryo and fetus, the blood is getting
oxygenated in the placenta. We need to send the circulatory system out to the placenta, and then
the blood comes back, so the placenta is part of the systemic circuit, the left side is pumping
blood out to the placenta and it is coming back via the veins to the right side of the heart. In the
fetus, oxygen levels are highest in the veins coming back to the heart. In the fetus, the blood
coming back from the veins is high in oxygen, we do not need to pump it to the lungs. The lungs
are not even in contact with air and we already oxygenated the blood, so we want to get the
blood to bypass the lungs and get to the left side. There are two bypasses: one takes blood out of
the right atrium and sends it across to the left atrium, this connection is the foraminal valley, the
oval hole, and then sometimes blood will still eject out of the pulmonary trunk, so we have
another bypass that takes blood out of the pulmonary trunk and moves it into the aorta, called the
ductus arteriosis.
The last thing we need to talk about before fetal development is the placenta. The
placenta has a number of functions: respiration, digestion, excretion, and producing hormones.

On the maternal side, the maternal circulatory system comes to the edge of the placenta, and the
umbilical arteries form a very complicated capillary bed on the fetal side, then the umbilical
veins go back into the fetus. On the placental side, we will simply dump off our carbon dioxide,
it will diffuse into the maternal circulatory system, and then she will exhale it. On the maternal
side, oxygen will diffuse out of the maternal circulatory system and into the placenta where it is
picked up by the fetal circulatory system, so the placenta acts as a respiratory membrane.
Similarly, to get its nutrition, the fetal blood comes indirectly in contact with the maternal
circulatory system; the two bloods do not mix at all, the cellular components are separate, but
nutrients can diffuse out just as they would in any other part of the body, and then maternal
nutrients are picked up by the fetal circulatory system and delivered to the cells of the fetus, so
here the placenta acts as a digestive organ. Also, all the waste produced by fetal cells simply
diffuse out of the placenta, and those wastes are picked up by the maternal circulatory system
and delivered to her liver and kidney to be processed, so here it acts as an excretory organ. In
addition, it is also an endocrine organ; up to this point in time, the conceptus needed the
endometrium as a force of oxygen and nutrients. What has been keeping the endometrium alive?
Estrogen and progesterone from the corpus luteum. And what is keeping the corpus luteum
alive? HCG. So now we do not need the endometrium anymore, so we do not need HCG
anymore, but we still need estrogen and progesterone, but if we are not going to make HCG
anymore and the corpus luteum is going to die, what is going to make the estrogen and
progesterone? The placenta makes the estrogen and progesterone. The placenta will make a
number of unique hormones also, to co-op maternal physiology: HCT, human corionic
thyrotropin, which increases maternal metabolism, that is why pregnant women have a much
greater appetite; HCS, human corionic somatomamotrophin, causes the mammary glands to

mature; HPL, human placentolactinogen, causes the maternal metabolism to stop using glucose
but instead use other things like lipids and aminoacids, this causes glucose levels to become
higher in the mother so that the fetus has that glucose. The fetus uses exclusively glucose to
develop. If you have ever heard of gestational diabetes, that is because of HPL. One last
hormone is relaxin, which causes the connective tissues of bones in the pelvis to relax, and as a
consequence, those six different bones that are fused together, in the front, and in the back, all
those connections loosen to let the pelvis get broader, which increases the dimensions of the
pelvic floor making childbirth easier.
Now we are at the end of embryological development and we enter into the fetal stage of
development. At this point, you are about 1 inch and weigh about 1 gram, or .03 ounces; it
seems like you are insignificant, and that is sometimes how we can marginalize this stage of life,
because you are physically insignificant from a size perspective, but at this point in time, you
have a fully functioning cardiovascular system and all your organ systems are present; all your
limbs are there, but everything is webbed together. At that point in time, you enter into the fetal
development. When you are an embryo, your head and body are about the same size, and then
slowly as you develop, the proportions change and the head gets smaller relative to the body, but
even the neonate has a big head relative to its body.
During the third month of development, the epidermis forms, you get some crude facial
features, the sex can be determined, all the limbs are there, and by the end of the third month you
are about 3.5 inches long, so you have tripled your size.
Then going into the fourth month, the nervous system continues to develop and by this
point the sensory organs have developed, you have eyes, ears, taste buds, and the olfactory

system; the eyelids can open and close, there is already primitive sucking motions. At this point,
the face looks very human.
Going into the fifth month, the body is getting very big and it is occupying too much
space within the uterus, you have gone from being 6 inches at the end of four months to 8 inches
at the end of five months, and that is when the fetus assumes fetal position, the limbs and knees
are folded toward the chest. Because of that skin to skin contact, to prevent the tissue from
growing into itself, the skin produces a very oily secretion that prevents the skin from sticking to
itself, and that is called the vernix casiosa. In addition, the dermal layer which produces hair
produces a very fine, silk like hair that covers the body, reducing the ability of cells to grow
together between different body regions. At that point, because the fetus is big enough, the
mother can actually detect the movement of the fetus. In history, that is when the fetus was
considered to be alive, that movement that is detectable by the mother was called quickening.
In the sixth and seventh month, you reach the ability of independent survival; around the
28th week the type II aviolar cells would make surfactin, that would allow the lung tissue not to
stick to itself, at this point, if the fetus were to be born, it would be able to independently respire,
but it cannot thermoregulate yet, it cannot maintain its own temperature because it does not have
any subcutaneous adipose. At the end of the seventh month, even though independent respiration
is possible, the neonate would have to be kept in a controlled temperature environment.
During the last two months, the fetus grows bigger, puts down subcutaneous adipose. At
the end of seven months, the fetus is about 12 inches long and it will grow another 50% over the
course of the two months.
The process of giving birth to the fetus is a multistage process. The first thing that has to
happen is that the process has to be initiated; once it is initiated, the next thing that has to happen

is the cervix has to be prepared to allow the fetus to pass through, which is stage I labor; once
that happens the fetus is delivered into the vaginal canal and outside of the body, which is stage
II labor; the last thing that needs to happen is that the placenta has to be delivered also, which is
stage III labor.
The term labor refers to all of these events. How it is initiated is not totally understood,
but near the end of pregnancy, estrogen levels get really high, which inhibits the production of
progesterone. Progesterone has been primarily there to inhibit a lot of other activities, such as
the production of oxytocin receptors. Other things that were otherwise being negatively
controlled are released. Oxytocin receptors are now formed in the myometrium, and that now
makes the muscle of the uterus spontaneously contract. This is when the woman might mistake
those sensations as giving birth, called the braxton hicks contractions, false labor. That is
spontaneous, and that simply signals that labor is soon going to happen, maybe a week or a
couple days later. Then the placenta will release oxytocin, not the posterior pituitary, to cause the
myometrium to contact. Now we have started labor, with the myometrium contacting. The
effect of the oxytocin is not to cause what is called stage II labor; it causes the release of an
inflammatory agent called prostaglandis, which makes the myometrium very irritable, and
stimulates the uterine muscle and beings to contract.
Now that labor is started, the first challenge during labor is to push a very large object
through a very small hole. The fetal head is about 10 cm, the cervical canal is about 3mm. Now
we need to ram a 10 cm object through a 3 mm hole. What happens during stage I labor is that
the myometrium contacts and presses the head of the fetus into the back of the cervix, and holds
it there, then releases, then presses the fetal head into the back of the cervix again, and over and
over again, for maybe 8-12 hours. It is like preparing veal, you hit it a couple hundred times

with the meat hammer and it becomes very thin. That is what happens with the cervix, it goes
from being a very broad structure to a very thin structure, so as you stretch it out laterally, the
hole gets bigger. During stage I labor, we efface the cervix, meaning make it thinner, therefore
making the cervical canal dilate. Once the cervix is effaced, the head will slip through the cervix
and enter into the pelvis, and that is called presentation.
The head is now in the pelvis, and we are ready for stage II labor, and this is when
oxytocin is helpful. At this point, the irritability in the uterus is perceivable by the nervous
system, which activates the neurons that release oxytocin. Oxytocin activates the upper part of
the myometrium and pushes the fetus down through the cervix and into the vaginal canal, which
is some pretty intense contractions. Hopefully, without too much injury to the vaginal orifice,
the top of the fetal head emerges out of the vaginal canal, which is called crowning, and they use
a little suction cup to pull the fetus out.
Stage III labor, sometimes called the afterbirth, is just delivering the placenta.