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Development of Bilaminar Embryo
11-6-09
1. Introduction
a. The fetus is upside down, head down in the uterus and amniotic cavity since it fits best
this way
b. The legs have more room to move around in the upper portion of the amniotic cavity.
c. Due to the positioning of the uterus, women in the final stages of pregnancy have to pee
a lot because of pressure of the uterus on the urinary bladder
d. The umbilical cord attaches at the naval(umbilicus) of the fetus and extends with it’s
vessels over into the placenta which is imbedded in the wall of the uterus.
e. The great majority of the time implantation of the developing embryo occurs on the
posterior wall
i. Anteriorly placed placenta makes it difficult to do a C-section delivery
f. Occasionally (as is the case with the example shown in class), the growing fetus,
specifically the placenta rests on the lower spine compression the vena cava return from
the lower limbs
i. Causing pain, swelling, etc
2. The placenta
a. The umbilical cord and it’s blood vessels lead into the extraembryonic tissues consisting
of the placenta, chorionic sac, and smooth chorion
b. The placenta itself is the exchange organ between the mother and fetus
i. Oxygen, nutrients, and wastes of the fetus all pass through the maternal and
fetal blood through the placenta
c. The umblicial cord can be seen going into the fetal aspect of the placenta and dividing
out into branches that will ramify on the fetal surface and divide into smaller and
smaller branches that will vascularize the fetal tissues themselves
d. The fluid contained within the intact amniochorionic membrane is amniotic fluid.
e. Looking at the maternal aspects of the placenta it appears quite rough, bulge like known
as cotyledons
i. Cotlyedons are filled with placenta villi and blood
ii. Looking at the maternal aspects we also see some maternal tissue
(endometrium) with fetal tissue deep to it
iii. After the placenta is delivered (3rd stage), the placenta must be checked to see if
it complete and that there are no missing parts
1. This is important because the embryo fetus needs the placenta to
survive but not the other way around
2. Thus, if placental tissue is retained in the uterus it can continue to go
through metabolism and grow while not following normal cellular
controls and become a malignancy
iv. If we break open one of the cotelydons we can see running within it small
vessels leading out into a very spongy area (finger like area) which are the villi
f. Placenta also creates hormones that affect mother’s body
g. Placenta has also been used in cosmetics
3. Fertilization
a. The ovary is the gonad that produces oocyte follicles during development
1
b. One of the developing follicles will be chosen to complete development and ovulate
releasing secondary oocyte, cells, and other tissues which will be released into the
peritoneal cavity and hopefully be picked up by the uterine tube
i. Ovulation is usually the 11th day of a 28 day uterine cycle
c. If spermatozoan are present, fertilization may take place
d. Unfortunately however, the thing that helps determine when menstrual or uterine
changes occur is not related to the first portion of the ovarian cycle, but rather the
second portion of the ovarian cycle
i. Or whether or not there is a degeneration and loss of function of the corpus
luteum
ii. The constant time within the ovarian cycle is that time period from ovulation to
the loss of function of the corpus luteum, which is 14 days
e. Preovulatory phase may be longer or shorter than 14 days
i. If the womans ovarian cycles are regular than you can figure out the
approximate time ovulation should occur.
ii. However, if she is not regular, it is impossible to accurately determine when
ovulation is taking place
iii. The day of or the day immediate following ovulation are considered a woman’s
fertile period
f. Ovulated mass is released from ovary and is picked up by the uterine tube. This happens
because the end of the uterine tube caps the site of ovulation on the ovary so that the
egg can be picked up
i. There is a chance that the ovum and associated eggs will fall into the peritoneal
cavity, however this typically does not happen (if fertilization happens any place
but the uterus it is considered an ectopic pregnancy
2
g. Remnants of follicle the remain in the ovary transform into the corpus luteum (yellow
body)
i. This produces progesterone which is important because it causes the lining of
the uterus to change from proliferation to one that is secreting.
ii. The secreting form of the uterus will be receptive to the possible little one that
will be entering into the uterine cavity
h. Zona Pellucida
i.
i. Layer of noncellular material around oocyte
ii. Formed from contributions from the oocyte and follicular cells;
iii. Thus the zona pellucida is present is present within the ovary (since follicular
cells add to the zona peludica) as well as part of the ovulated mass.
iv. Functions
1. It serves as the binding site for spermatozoa (contains binding sites on
its surface)
2. Limits the number of spermatozoan that will try to fertilize oocyte
3. Holds together the small mass of early cells that results just after
fertilization (thus preventing them from wandering away
4. Also prevents fertilized cells from making contact with maternal tissue
The forming of the Conceptus
i. Conceptus relates to the products of fertilization
1. Includes the embryo proper and all extraembryonic tissues (such as the
placenta)
2. Everything that results from fertilization has the same genome (that
which results from fertilization)
ii. Follicular cells (corona radiata) probably make the ovulated mass a little larger
and make it rough on its surface so the uterine tube can handle the mass more
easily because it has been shown if you put the oocyte and zona without the
corona radiate it will just sit and spin within the uterine tube instead of being
transported further down the tube
1. These extra cells make it a larger mass, easier to handle for the uterine
tube, and further the corona radiate (which originally are follicular cells)
are probably releasing compounds that attract the spermatozoa if they
are close enough
iii. Thus the first spermatozoa must disperse the corona radiate so that later sperm
can break through the zona pellucid
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1. The head of the spermatozoa (the acrosome) contains enzymes
2. One of these enzymes released from the acrosomal vesicle is
hyaluronidase which will help break down the matrix and cell adhesions
between the cells of the corona radiate
3. Subsequent sperm make contact with the zona and bind to it
a. These sperm’s acrosomal reaction will release enzymes will
forge a path through the acellular zona pellucida
iv. The plasmalemma (cell membrane) of the oocyte is against the zona pellucida
1. In fact, right before ovulation the oocyte has microvilli that go into the
zona pellucida so that when spermatozoa digest their way through the
zit they can make contact with the plasmelemma of the oocyte
2. The membranes of the spermatozoa and that of the occyte fuse, break
open, and the contents of sperm go into the cytoplasm of the oocyte
a. The nucleus, the mitochondria, and the flagella go into the
oocyte
b. The nucleus survives, will the mitochondria and flagella
degenerate
v. Cortical Granule and zona reaction
1. As a result of the spermatozoa penetration of the occyte, granules are
released that were on the edge of the occyte out in the cortex of the
occyte
2. The contents of these granules get into the previtiline space (cortical
granule reaction)
3. The contents of the granules are released and cause a chemical change
in the zona pellucida
4. In addition to the above reaction, the plasmalemma of the oocyte
retracts from the zona and makes a true previtiline space
a. When the plasmalemma retracts it prevents additional
spermatozoa that were piercing the zona pellucida to make
contact with the occyte (which has not retracted) as the sperm
flagella is no longer effective
b. This prevents the oocyte from being fertilized by more than one
sperm for about 20 min or so
4
5. The chemical change to the zona pellucida takes ~20-30 minutes (zona
reaction)
a. The chemical change prevents the acrosomal enzymes from
being able to penetrate the zona pellucida, thus preventing
polyspermy
i. If polyspermy does occur, often times the pregnancy
will spontaneously abort either early or later
4. The Developing embryo
a. As mentioned before, tissue remaining with the ovary becomes the corpus luteum
producing progesterone which causes the lining of the uterus to change from the
proliferative phase (stimulated by estrogen) to the secretory phase (receptive phase)
b. Fertilization completes meiosis (specifically the second meiotic division)
c. Now the male pronucleus is within the oocyte cytoplasm. When the female and male
pronuclei merge the normal genetic component is created
d. Replication and mitosis then begins to occur.
e. Genetic variation happens because of maternal and paternal genomes have altered or
triggered the metabolic processes within the cell to begin mitosis
f. The beginning cell divisions take place as the conceptus is moving down the uterine tube
still surrounded by the zona pellucida (which functionally holds the developing embryo
together)—the radiate has now disappeared
g. Within the developing embryo the first polar body given off by meiosis 2 and the first
mitotic division results in two equal cells
i. These 2 cells divide, then 4 cells, then 8 cells, etc
ii. As we have mitotic division, the cells are getting smaller
iii. Early mitotic divisions are just separating the initial cytoplasm but as they do
they are producing more nuclei
iv. Thus more cells are produced but each will temporarily be smaller
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1. Part of that is through the process of keeping cells all contained within
the zona pellucida not letting them abide fluid and swell up
2. But there are probably also cell-cell reactions that are helping to
produce the reaction known as compaction
a. Cells getting smaller and having more contact with each other
h. What will happen as we get more cells is that some cells find themselves on the inside
of the ball of cells and others will gravitate towards the outside
i. Through cell to cell interactions, cells figure out who is on the inside and outside
j. If I am a cell on the outside and I am destined to be a certain type of tissue and if I am
on the inside destined to be a different type of tissue triggered by the positional
relationship
i. To illustrate this point, if we were to take cells at this stage and artificially them
and let them come back together again, the cells that were on the side would
not necessarily be on the inside again or visa versa, they rearrange themselves
based on cell-cell interactions
ii. However, somewhere along the way based on cell position a decision needs to
be made what cells will be supporting cells and what will become a new
individual
k. ~4-5 days after fertilization the zona pellucida will break down
i. The result of the enzymes produced by the sperm and other reactions with
maternal tissue during the progress down the uterine tube will slowly cause this
to occur
ii. This allows the small compact ball of cells that may or may not have a cavity in it
to “hatch out” of the zona pellucida causing the cells to become uncovered and
the cells to enlarge, making the whole conceptus larger
l. The small cavity within the cavity gets larger and larger and lineation between the cells
on the inside and outside can be seen better
m. So as we complete meiosis we throw off 2 polar bodies depending if the first polar body
divides, mitosis begins, up to ~ the 32 cell stage the mitotic divisions are
6
synchronous..However after this stage it becomes asynchronous growing at different
rates
i. The 32 cell ball of cells (morula) are probably fighting it out to see who is on the
inside and outside
ii. As soon as the zona pellucida breaks down the conceptus can swell up and the
blastocystic cavity becomes more obvious. And the morula transforms into the
blastocyst (meaning having a cavity within it.
5. The parts of the Blastocysts and early stages of implantation
a. The inner cell mast inside the blastocysts can also be referred to as the embryoblast (as
these cells will give rise to the new person
i. The inner cell mast can be divided into two parts
1. Epiblast (which later breaks down into three parts)
a. Ectoderm
b. Mesoderm
c. Endoderm
2. Hypoblast
a. Gives rise to the extraembryonic mesoderm
b. Outer cell mast is known as the trophoblast (blastoform—which means to feed or
support)
i. The trophoblast ultimately differentiates into cells that will make up
cytotrophoblast (the portion of the trophoblast that retains discrete cellularity)
1. Cytotrophblasts are a reserve cell population (a proliferating cell
population)
ii. The other differentiating portion of the trophoblast is the synctiotrophoblast
which is part of the outer cell mass with a multinucleated cytoplasmic mass with
many nuclei and organelles functioning as one big cell
1. Thus the synctiotrophoblast is the differentiated tissue of the
trophoblast
2. When we said earlier that the placenta is made of trophoblastic tissue is
making hormones etc it is actually the synctiotrophoblast that is
producing these substances
a. It is the more mature, differentiated, specialized tissue
3. As said earlier the cytotrophblasts are the reserve undifferentiated cells
a. Perhaps cytotrophoblastic cells as they proliferate can merge
and break down their cell membranes and let their cell
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membranes and cytoplasms become a common pool as their
individual plasmallema fuse contributing to the extensive
plasmalemma of the synctiotrophoblast
4. The synctiotrophoblast then furter differentiates to become productive
tissues
iii. All trophoblastic structures can be lumped together and called the chorion
6. General outline of development
a. The embryo proper transitions into the fetus and into a neonate
i. The embryo typically refers to the developing individual in the first 8 weeks
ii. At the end of 8 weeks, all of the organ systems within the body have at least
started to develop
b. The fetal period is from 8 weeks to 38 weeks
i. Further growth and differentiation occurs during this time
ii. At the time of labor the little one is a fetus, not an embryo
c. The syntiotrophoblast, the connective tissues outside the embryo, and the
cytotrophoblast (all outer cell mass structures) will be called the chorion
7. Embryo Implantation
a. The endometrium is the mucosal lining of the uterus and will have epithelium on the
surface and epithelium glands going into the underling stroma and many blood vessels
b. It is the endometrium that undergoes changes of the uterine cycle driven by the ovarian
cycle
c. The myometrium is the muscular layer of the uterus. The endometrium lines this layer.
However the major bulk of the uterus is the myometrium
d. Implantation is the process by which the conceptus attaches to and grows into the
endometrium
e. Because the embryo grows into the endometrium breaking through the epithelial tissue
is an invasive process
8
i. The conceptus invades the maternal tissues, with permission granted by
maternal tissues
1. The conceptus sends out chemical signals and the endometrium
responds so it is permissive invasion
ii. The conceptus ends up being totally embedded in the endometrium in the
interstitial space of the endometrium
1. Hence we as humans are said to have an interstitial implantation ,
meaning the conceptus has grown into and occupies extra and
intracellular space of the endometrium
iii. In other animals the conceptus stays in the uterine cavity and may have an
appositional relationship with the endometrium of that species
iv. With interstitial implantation and the way we have maternal blood going into
fetal tissues we as humans have the most intimate relationship between the
mother and developing child
1. Basically, humans posses the least barrier between maternal and fetal
blood of any species
f.
The Disiduum
i. Altered endometrial stroma. Happens as a result of implantation.
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1. Chemicals released by conceptus will cause changes within the stromal
cells (CT cells) of the endometrium.
2. The cells begin to accumulate glycogen, they swell up and become
larger
ii. The reaction that relates to the implantation process is called the disidual
reaction
1. This resulting cells of this reaction are altered stromal cells which will
provide a nutrient source as they break down or are broken down by
the conceptus very early on.
iii. The altered environment of the now disidua also alters the lymphocytes that
live in the interstitial spaces (intercellular lymphocytes) that live in the disidual
spaces and down regulates the ability of T-lymphocytes to recognize foreign
material
1. Thus as a result of the implantation and reaction of the endometrium
the conceptus is provided transient nutrient source but more
importantly and immunological sequestered area to develop in
2. The lymphocytes that are in the disidua cannot recognize non-self as
readily
iv. The disdua can be broken down into 3 major areas
1. The disidua basalis which is between the conceptus and the
myometrium
a. As we will see, the conceptus is in the cavity of the uterus,
invades into the endometrium from the epithelial surface, there
is still connective tissue of the endometrium between the
conceptus and the myometrium (which obviously is more basal
to the implantation site (the dicidual basalis)
b. Because the conceptus has grown all the way into the
endometrium, as the conceptus enlarges, it bulges out the
endometrium around it
2. For a period of time the altered endometrium forms a capsule over the
expanding conceptus between the conceptus and the uterine cavity
called the decidua capsularis
3. The everything else that is not directly related to the implantation site
either basal or capsular to it is the dicidua paratalis (which mean wall)
a. Thus the paratalis is all of the altered endometrium not directly
related to the implantation site which is basalis and capsularis
v. The conceptus is expanded out into the uterine cavity so the endometrium
undergoes changes triggered by the implantation (chemicals released by the
conceptus)
1. The disidual reaction takes places first at the implantation site and then
spreads so that all endometrium is involved.
2. The word decidua means “shedding off”
3. Thus the dicidua (the altered endometrium) is lost at the time of
parturion with the extraembryonic membranes (expulsion of the
placenta after birth) and then the normal endometrium is established
8. The Forming of the Placenta
a. 5-6 days old by the time the conceptus is in the uterine cavity
b. By this time the zona pellucida has disappeared
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c. The conceptus has differentiated into a trophoblast and embryoblast
i. So the cells of that early conceptus have already established through mutual
agreement if you will who is going to be the supporting cells and who is going to
be the new individual
d. With no zona pellucida present, the trophoblastic cells can make contact with the
endometrial (maternal) tissue
e. As it does this there are signals moving back and forth through the fluid within the
uterine cavity between the conceptus and endometrium, developing a hand shake
relationship
i. As said before it is not just an invasion, it is a permissive invasion
f. The trophoblast comes in contact with endometrial tissues and it is usually going to be
in the area of the trophoblast that overlies the embryoblast
i. For some reason these cells are “stickier”
g. At the embryonic pole of the conceptus, the trophoblastic cells have slightly different
properties then at the abembryonic pole
i. Hence it is a little bit easier to stick to the maternal tissue at the embryonic pole
h. Contact between the trophoblast and endometrial tissues triggers trophoblastic
proliferation and the proliferated cells merge together to form the synctiotrophoblast
i. Cells of trophoblastic origin that retain their discrete cellular identity remain as
cytotrophoblast.
i. If the cytotrophblastic cells are in the area where synctiotrophoblast is being
formed, the cyto- cells will undergo mitotic division and many of the daughter
cells will be added to the synctiotrophoblast
ii. Some of the daughter cells will remain behind as reserve population cells to
undergo further mitosis
j. Within the synctiotrophoblast the nuclei will undergo mitosis
i. The syn- cells through enzymatic activity, etc, begin to break through the
epithelium of the endometrium invading into the underlying stroma (CT)
1. Permissive invasion
2. If the endometrium does not respond, the conceptus can send out all
the signals and develop the best synctiotroblast possible but not be able
to implant thus causing infertility called endometrium nonreceptiveness
3. As the syn- invades the endometrium, the rest of the conceptus follows
along
4. As more trophoblast makes contact with more maternal tissues, more
syntiotrophblast is formed
k. “Lacuna means little leg”
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i. If you think back to cartilage and bone, lacunae contain the cells within the
matrix
ii. In terms of development, lacunae are membrane bound spaces within the
synctiotrophoblast
1. As stated before the syn- is a multinucleated cytoplasmic mass
2. Within the cytoplasmic mass are all the organelles needed for protein,
steroid, etc, production (in general metabolism)
3. The syn- can develop membrane bound spaces within the general
cytoplasm
4. Now these membrane bound spaces, since they are in maternal tissues,
will not be filled with air but instead filled with fluid because maternal
fluids are permeating through the conceptus
5. The lacunae will join together and become known as the innervillus
space (space within the more mature placenta in between the villus
projections)
a. This innervillus space will contain maternal blood
6. Within the villi, we will have fetal blood vessels obtaining fetal blood.
7. So we see these areas within the synctiotrophoblast which are the
developing lacunae
a. Because ultimately these places will be filled with maternal
blood
8. Syn- and conceptus tissue is invading in, the syn- is absorbing break
down products from stromal cells that have undergone disidual
reactions receiving or absorbing products from the glands that were rich
12
l.
in glycogen and other nucleopolysaccharide material that can diffuse
though synctiotrophoblast thus nourishing it and moving on into deep
structures
9. But as the synctiotrophoblast and conceptus migrates further in, it
comes in contact with maternal endometrial blood vessels and the synengulfs these, breaking into the maternal blood vessels
10. The syn- literally caps around the outside the luminal aspect of the
blood vessel so it physically breaks down the vessel wall and forms a
capping mechanism over the ends so there is no blood leakage
11. Now it is possible for the maternal blood to leak into the lucunar spaces
12. As lacunar spaces join together and syntiotrophblast taps into larger
and larger vessels, it will get into more of the arterial aspect of the
maternal vessels and larger venous aspects of disidual vessels and now
will develop a circulation
13. Maternal blood released into lacunar spaces (developing innervillus
spaces) coming out of the endometrial arterioles (ultimately arteries),
circulating through the space technically outside the mothers circulation
and then draining into maternal veins.
14. Thus the conceptus during this implantation process has opened up a
shunt in maternal circulation.
As the syn- continues to develop and the conceptus invades further and further in will
ultimately have syn- form all the way around the conceptus.
i. Remember the syn- is the differentiated tissue
ii. Part of its differentiation is that it does not elaborate many surface antigens so
even though the endometrium is a preferred sequested area immunologically,
also the conceptus itself is practicing stealth technology by not elaborating a lot
of surface antigens that would flag down the immune system saying “I am not
self”
1. Thus these two things work together
iii. The syn- is invading in and as it continues to enlarge we continue to have
cellular proliferation in the cyto- and in the areas of the cyto- we begin to get
some proliferation and begin to get accumulations of cells that will begin to
penetrate into the syn-, kind of like going in between the lacunar spaces
iv. We are developing some finger like projections and these are called primary villi
v. Thus the primary villus will have syn- around the outside and a cyto-core,
eventually getting cyto deeper into synvi. We have developed syn- all the way around around the conceptus and tapped
into blood vessels all the way around the conceptus
vii. Cyto- is growing out into the overlying syn- all the way around ultimately some
tissue known as extraembryonic mesoderm will grow into the vill
13
1. The extraeembryonic mesoderm is developed from the hypoblast
a. We have villus formation going into the innervillus space areas
that now in addition to the syn- and cyto- have extraembyonic
mesoderm which is a form of CT
b. Anytime you here the word mesoderm think CT amoung other
things
c. This CT is outside the embryo proper thus being called
extraembryonic mesoderm
d. The syn, cyto, and invadining extraembryonic mesoderm is
known as a secondary villus
viii. Time proceeds, the cyto- has grown through the syn and even makes it to the
outside where it comes in contact with the disidua (altered mesoderm)
1. Thus making a cyto- shall around the outside
2. However, even though the cyto- cells have surface antigens on them,
the lymphocytes in the area cannot detect foreign material because of
disidual reaction dicussed earlier
3. The extraembryonic mesoderm that had grown into those villi and
formed on the inner aspect of the trophoblast is differentiating and
gives rise to blood vessels
4. So now in this developing trophoblastic cell supporing tissue we have
BVs forming
5. The BVs here in what will ultimately become placenta will ultimately
connect with BV developing in the embryo proper and the early
developing umbilical cord
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ix. Now has been established fetal primitive fetal placental circulation
1. Maternal blood is coming into what was the lacunae and now is the
innervillus space circulating through that.
2. Fetal blood is going to be moving through the fetal BVs within the villi
3. Materials will diffuse across this so called barrier or be carried across by
facilitated diffusion or active transport
4. Notice that we have BVs, syn, all the way around the conceptus
m. Review
i. Trophoblastic cells have different properties ( more sticky) than other cells
ii. When they come in contact with maternal tissue the cells proliferate to from
syn15
iii. Syn- knows to invade with permission
iv. Invades through the epithelium through basal lamina into underlying stroma
endometrium that is going to begin to trigger disidual changes within that area
v. Lacunae are within the syn- and contain maternal blood
vi. Only tissue of conceptus that maternal blood will come in contact with is synvii. Syn- develops ALL the way around the BV
1. As we look at this, you can envision that if this happens to tap into a
rather large artery early on, the syn- does not have much strength and
hemmorage out which is a reason for early spontaneous abortion called
implantation bleeding
viii. We are developing innervillus space and inbetween villi are the maternal blood
containing spaces
ix. The villi themselves will consist of syn- on their outer surface, cyto on the inside,
and also extraembyronic mesoderm which will make umblicius BVs
x. Primary villus is syn and cyto
xi. Secondary is syn, cyto, and extraembyronic mesoderm
xii. Tertiary is syn, cyto, extraembyonic mesoderm and BV
xiii. Notice cyto has gone to the outside moving around but disidual reaction has
been completed so it does not trigger an immune response, the cytoproliferation could add to the syn- on the outer aspect
xiv. Up until mid pregnancy, material must diffuse through syntio, cyto,
extraembryonic mesoderm, and fetal capillary endothelial cells
xv. But during the second half of pregnancy, much of the cyto has been used up or
degenerated and the fetal BVs marginate ( move to outside of villus) so that the
only layers that material must pass through would be syn, its basal lamina, the
basal lamina of fetal BVs and the endothelium of fetal BV.
1. Thus it is not a very strong membrane (barrier)
xvi. Also, we can see those villi that we looked at can be branching to increase
surface area
xvii. All the good nutrients make it through the placental membrane from maternal
blood to fetal blood
xviii. Waste products go the other direction to be eliminated by kidney or lungs
within the mother.
1. However, harmful things such as viruses, CO, drugs, alcohol, poisons,
microbiological organisms capable of moving on their own are able to
penetrate the barrier
2. Bacteria usually do not make it through
xix. Shown below is a schematic of the placenta in side view, fetal BV coming down
into villi.
1. The villi form especially where maternal arterial blood is coming into the
innervillus space
xx. In between those fountains of maternal arterial blood villi do not form so the
placental tissue doesn’t enlarge as much and will form partial septa
xxi. Now if you think back when we looked at the placenta we looked rough on
maternal aspect, the cotelydens and the spaces in between,
1. cotelydens form because of augmented villus formation takes up space
triggered by maternal arterial blood
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2. This is where we do not have input of arterial maternal blood therefore
not as much villus formation and we develop then the septation around
the cotelydens
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