Early Embryonic Development 1

Dr. Johnson
Week 6, Friday 9/18/14
Lesson Objectives
1. Review events of ovulation and fertilization
2. Describe timing of early development
3. Understand totipotency of early blastomeres
4. Understand in vitro fertilization
5. Describe normal implantation
6. Understand clinical presentation of abnormal implantation
PART 1: Ovulation
A. Overview
1. This event occurs mid-cycle of menstruation
2. During this event, the secondary oocyte, the zona pellucida,
the corona radiata and mass of mucus known as the liquor folliculi are
ALL released
3. After being released, this collection is set off into the ciliated
epithelium of the uterine tubes and swept into the lumen of the female
reproductive tract..the mucus is sooo important in that the cilia can
use that to push this collection down the tubes

4. What am I looking at? This shows the preovulatory follicle that

houses a primary oocyte, stuck in meiosis I, at metaphase. The next
image is the ovulatory event when the secondary oocyte is released
with the corona radiata, zona pullicida, and mucus. At this point the
secondary oocyte is stuck in Meiosis II awaiting fertilization . IN the
third stage, the follicular cells remaining will transition into luteal cells
that will form the corpus luteum. There is mitotic division increasing
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the cell amount of the corpus luteum and the inside of the follicle is
filled with fibrin.
5. The important things to know here are that the LH surge
produced by the pituitary gland is what causes the follicle to rupture, it
triggers the completion and division of meiosis I with polar body 1
production and the ovulatory event to occur. The corpus luteum that is
left behind serves as an endocrine organ and will release progesterone
to prepare the lining of the uterus by increasing vascularization of the
endothelium.

6. This image is showing the uterine tube and ovary in better

detail. Look at how the fimbriae of the fallopian tubes are finger like
projections that will catch the released oocytehowever, note that the
uterine tube is open to the peritoneal cavity, if the oocyte does not
properly travel down the tube toward the uterus it can float off into the
abd cavity. The tube works via peristalsis to push the oocyte down
toward the uterus. Uterine infections can also cause peritoneal
infections
*This shows the ovulated secondary
oocyte, There are a lot of follicular cells
attached to the outside of the zona
pellucida

B. Corpus Luteum
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1. The remnants of the mature follicle becomes the corpus

luteum
2. Granulosa and thecal cells differentiate(luteinize) forming
apparatus for steroid biosynthesis
3. The corpus luteum will release progesterone, which is a
hormone that supports implantation which would occur during the
second half of the ovulatory cycle. This hormone affects the glands in
the uterine lining, making them secretory and the glands start to
secrete trophic and stimulatory factors

PART 2: Fertilization
A. Consequences
1. Triggers meiosis II in secondary oocyte which results in the
production of a second polar body and an ovum
2. There various steps that contribute to fertilization: block to
polyspermy, reestablish polyploidy, initiate developmental program,
determine genetic sex

3. You can see that the sperm attach to the ovum externally and
fight to enter the cell. Once a sperm successfully reaches the cell, it
will trigger the completion of meiosis II. The sperm will then release its
nucleus into the ovum and the cell will be officially diploidy at this
point. This diploid cell will then undergo cell division resulting in the
two-cell stage

4. The texbooks will say that the two cell stage is succeeded by
even numbered cell divisions, however in real life it is asynchronous.
The zona pullicida remains intact because the cells are not yet
attached to each other. So after about 1 day following fertilization the
two cell stage will be reached, at 40 hours that 4 cell stage will be
reached and after 4 days will be the morula stage which is more than
16 cells(maybe 50 cells). The morula has not yet reached the uterine
lining. Note the cells of the embryo are called blastomeres.

5. This image on the left is showing the sperm attached to the

growing and dividing cell. The image on the right shows about the 20
cell stage
B. Compaction
1. Individual blastomeres have changes in cell surface chemistry
and they now adhere strongly to one another
2. This creates the outer and inner population of cells
3. Both populations continue to divide, producing the trophoblast
and embryoblast(inner cell mass). The trophoblast will develop into the
placenta and fetal membranes and will be on the polar end of the
developing embryo
4. When cells on the outside of the morula change structure and
become tightly adherent, this is the first obvious differentiation of the
embryo

5. The tight junctions between the epithelial cells that surround

the cells hold the cells together. The image on the right is post
compaction and the left is the precompaction morula.
C. Early Blastomeres are Totipotent
1. Removal of early blastomeres still results in formation of
complete fetus, thus blastomere biopsy possible for prenatal genetic
diagnosis
2. Dyes injected into one of four blastomeres end up in both
trophoblast and embryoblast
3. Therefore, early blastomeres are totipotent. This means they
are not differentiated in the morula stage of 4 cells so they are NOT
predestined to form a certain part of the body.
4. For the sake of nomenclature, the blastomeres are the cells
that divide within the morula
D. In Vitro Fertilization
1. You have a patient with scarring and bloackage of uterine
tubes but otherwise healthy
2. Woman can be hormonally primed to multiple ovulatory events
in single cycle and secondary oocytes can be collected
3. An egg and sperm are mixed in culture dish in the lab
4. After fertilization, several early embryos are collected and
transferred into the uterus via canula
5. Woman can then become pregnant and deliver a normal baby
6. Risks include multiple pregnancies, there is a slight possible
increase of birth defects, but this is minimal and may be confounded
by genetics of parents who require IVF
7. Other options include artificial insemination, egg donation,
surrogate mother, screening for genetic defects, sex selection

8. An embryo will not be able to implant without the dissolution

of the zona pellucida, and this will happen after about 5 days after
fertilization. So after this time, the blastocyst will release hydrolytic
enzymes that will degrade the zona and the embryo can then implant.
In the pic you can see the inner cell mass which will develop into the
fetus and the trophoblast cells on the opposite end will form the
placenta. Note the zona consists of carbohydrates. The degradation of
the zona should occur once the blastocyst has reached the uterus to
prevent improper implantation
PART 3: Implantation
A. Implantation
1. Blastocyst hatches from zona pellucida
2. Blastocyst attaches at pole containing inner cell mass
3. Outer trophoblastic cells proliferate and fuse to form outer
syncytium
4. Results in formatio of inner cytotrophoblast CTB and superficial
syncytiotrophoblast STB. The CTB are one cell one nucleus layer,
however the STB is a syncytium so it consists of fused cells. The STB
burrows into maternal tissue and release enzymes that degrade
maternal tissue.
5. The blastocyst will always attach on the upper part of the
posterior uterus that way the placenta will be up top and there is a lot
of space for the growing uterus underneath
B. More Implantation

1.STB is an invasive motile layer, it will break down endometrial

epithelium and degrades the stroma
2. Maternal blood vessels open, bathing the STB
3. STB continues to invade and expand, forming irregular surface
with lacunae(surface irregularities).

4. The syncytiotrophoblasts form lacunae which will help to

expose more of the blastocyst to maternal blood supply. At this point
the embryo is doubling in size and volume each day or so. It is
completely dependent on maternal blood supply for oxygen and
nutrients-this is why lacunae are necessary

*Eventually the structure will be completely embedded into the

maternal tissue (endometrium). The inner cell mass forms 2 layers: an
epiblast and a hypoblast. The epiblast is increasing in number of cells
and thickening. The hypoblast is also increasing cell number. The inner
cell mass is what actually becomes the embryo

PART 4: Implantation Complications

A. Bilaminar Disc Stage
1. The inner cell mass forms two layers-epiblast and hypoblast
2. Trophoblast forms invasive layer of cells for implantation
3. These two layers the epiblast and hypoblast are sandwiched
together and will be contained within the chorion shell, which is
beginning to form the placenta.
B. Abnormal Implantation
1. An abnormal implantation is one that occurs in any site other
than the upper, posterior portion of the uterine body
2. An ectopic implantation(pregnancy) in any abnormal
implantation where development occurs outside of the uterine lumen
3. About 95% of all abnormal implantations are ectopic
implantations but the two are not synonymous
4. Placenta previa most common type of abnormal nonectopic
implantation

* #5 will cause placenta previa, #4 is interstitial

implantation(ectopic), #3 is tubal pregnancy(ectopic).
C. Ectopic Pregnancy
1. Defined as an implantation where development of conceptus
occurs outside the uterine lumen
2. About 95% of ectopic pregnancies occur in the uterine tubes,
but tubal pregnancy and ectopic pregnancy are not synonymous
3. Rest of ectopics occur at scattered sites, ex includes
mesentery, rectouterine pouch(of Douglas), ovary kidney, diaphragm,

etc
*Embryo can happily implant in the tube and eventually blow the
wall causing massive bleeding into the peritoneum: emergent surgery
needed
D. More on Abdominal Pregnancy

E. Ectopic Pregnancy is Common

1. About 90,000 cases/year in US
2. About 16/100 pregnancies
3. About 30 cases/year at GWUMC ED
F. Predisposing Factors
1. Prior pelvic surgery
2. Past history of IUD use
3. Pelvic Inflammatory Disease PID, Chlamydia trachomatis
infections, syphilis, gonorrhea
G. Signs and Symptoms of Rupture
1. Reproductively competent, sexually active, sudden onset of
unilateral lower quadrant pain
2. Distended firm abdomen with rebound tenderness
3. Normal temp, tachycardia, low BP, low Hct, +B-hCG
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H. Treatment
1. Early ultrasound when pregnant establishes implantation site
and can rule out or diagnose ectopic pregnancy
2. Unruptured- methotrexate(chemo drug that can be used to kill
the embryo) or surgical removal and repair
3. Ruptured- urgent surgical removal and repair

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