OOGENESIS

EMBRYOLOGY  Begins with the multiplication of the diploid oogonia

through multiple rounds of mitosis to produce  primary
Gynecology oocytes
Lecturer: Doc N.E.Raymundo o Reaching a peak number of 6-7M during the
first 10-12 weeks of gestation

We all know that ovulation and fertilization occurs in the Total number
ovaries and the fallopian tube. We said that female, after
First 10-12 wks AOG 6-7 M
puberty, you end up with monthly oocyte formation with
At birth 2-4 M
ovulation and that oocyte is expected that normally it will be
At menarche 400,000
inside the fallopian tube.
So if this oocyte present in the fallopian tube will be met
by your sperm, then fertilization will occur. Fertilization is a process What is important for you to take note is that the
wherein you have the meeting of the egg and the sperm. If ever female needs to recruit at least 1000 primordial follicle for one
there will be one sperm fertilizing the egg, everything stops there dominant follicle. So 1000 per month/cycle, you will only recruit
so that there will be no chance for other sperms to penetrate the one of the 1000 that will become dominant. So therefore if you
ovum and that fertilization process will create the 2-cell, the 4- start your menarche at the age of 12, count the number of
cell, the 8-cell until you create the morula or the ball of cells. months, kung 400 months ang total, that means after that 400
Then, there will be implantation. months you are now starting to go to into another cycle of your
Implantation usually occur at the area of endometrial life and that is menopause. So your reproductive phase where
lining. The most common site would be the posterior part of the you can get pregnant is only 400 months.
fundus. If ever there will be implantation, weeks then (?), there
will be formation of what we call primordial germ cell. This
primordial germ cells will also create in the future your oocyte, if MEIOSIS
female and your sperm if male.
What is happening in the cycle? Germ cells from the
male and the female are considered to be haploid. After
PRIMORDIAL GERM CELL fertilization, you end up with the diploid type of cell and that will
create another human being.
 The primordial germ cell (gonocytes) are large and
eosinophillic cells
 The meiotic process begins as mitosis is ending in the
o Originated from the endoderm in the dorsal
fetal ovary.
wall of the yolk sac
 Meiosis is the mechanism by which diploid organisms
o By 6 weeks, the primordial germ cells migrate
reduce their gametes to a haploid state so that they
to the gonadal ridges by way of the dorsal
can recombine again during fertilization to become
mesentery of hindgut.
diploid organisms.
 In humans, this process reduces 46 chromosomes (or 23
It is considered to be formed as early as 6 weeks AOG,
pairs) to 23 chromosome structures in the gamete.
just two weeks after fertilization, you will expect that there will be
 Meiosis is also the mechanism by which genetic
the formation or identification of these germ cells. And when you
exchange is completed through chiasma formation
look at the area of the germ cell, it is more at the gonadal ridge.
and crossing over between homologous chromosome
This development will progress as they go on to your
pairs.
embryogenesis. So in your embryogenesis, you create two ducts
– one is the Wolffian duct, and the other one is the Mullerian
During the process of folliculogenesis, in your
duct.
oocyte/spermatogenesis there will be meiosis. This meiosis will
Wolffian duct, which is also known as your mesonephric
create homologous chromosome that is considered later on to
duct, will give rise to the MALE structures of reproductive system
be the haploid. So there will be some change of your genetic
while that of the Mullerian duct, aka paramesonephric duct, it
material. Kaya hindi tayo kapareho ng parents natin. Hindi tayo
will now produce the FEMALE reproductive system. Now which is
mirror image. We are not a complete duplication of our parents
which? Hindi pa natin alam whether it will progress to a male or
because of this exchange of information.
into a female at this point. But what is important for you to take
note is that all embryo that is produced as early as 6 weeks AOG
 MEIOTIC DIVISION
will have a chance to become a male or a female: Pag male,
o Two meiotic cell divisions are required to
may Wolffian duct. Pag female, may Mullerian duct.
produce haploid gametes.
If ever it will become a female, there will be remnants
o Reproduction division, division I, or meiosis I
of the Wolffian ducts. These remnants are your oophoron and
 Occurs over a time span from fetal
paraoophoron.
life to menarche
As the development of Mullerian duct progresses, then
you will be able to see canalization on the female reproductive
What is also important for you take now is that there will
organ. There will be fusion of these Mullerian duct at the midline.
be reductions. Unlike in the male compared to the female,
There will be canalization after the fusion, and then you will see
pag tayo sa male nag duplicate, ALWAYS from a single
the formation of the uterine cavity, endocervical canal and the
magiging apat kaagad, and the later on that apat,
vaginal canal.
magiging 16. Unlike in the female, pag nagduplicate yung
oocyte, the other will become a polar body. Ibig sabihin, it
SOURCES OF GONAD DEVELOPMENT
will just become a part of the dominant follicle. Instead na
 Mesenchyme of gonadal ridges (plica genitalis)
nagduplicate sya into four, it will only come up with two
 Coelomic epithelium (mesodermal origin)
cells.
 Gonocytes (primordial cells)
There will always be meiosis and as much as possible, it
will be a duplication of only half of the cells. Ang meiosis you
will end up with FOUR HAPLOID, but during mitosis, ATLEAST

*felixthecat
 NAGIGING DALAWA LANG (TWO DIPLOID). That’s the
difference between meiosis and mitosis.
o Of the five stages, prophase I lasts the longest,
occurs exclusively during fetal life, and sets the
stage for genetic exchange that ensures
genetic variation in our species.
o The oocytes complete prophase before
entering a quiescent period.
 Re-entry into meiosis is signalled by the endocrine
changes of puberty
 In the mature cycle, usually one oocyte each month
will complete meiosis I as a function of ovulation and
meiosis II fertilization occurs.
 It is in fetal life that the ovary makes all of the oocytes
that the adult women will have for reproduction.
We always look at meiosis as a signal wherein there will
be a change from a newborn to your adulthood via your: 1,
pagnagkaron ng menarche, 2, if the male starts to
ejaculate.
PROPHASE STAGE
 Prophase stages of the first meiotic division occur in the
female during fetal life
 The meiotic process is arrested at the diplotene stages
of prophase I of meiosis I (first meiotic arrest) and the
oocyte enters the dictyotene stages
Your primary oocyte will be arresting will be resting on a
prophase stage. Later on it will go on the secondary oocyte
stage and become fertilized. Pag na-fertilized na, it will
become a zygote na.
 THE SPERM are attracted to an egg through the process known
Another thing for you to take note is that if ever the
primary oocyte will not be able to reach the secondary oocyte,
it will be absorbed. That is the reason, on why out fo 2-4M
oocytes at birth, nagiging 400, 000. Then out of 400,000 only 4,000
will go to fertilization, if ever. (Hindi ba 400 lang?) Therefore, we
can say that majority were not able to progress from primary to
secondary oocyte.
MEIOSIS I
 Resumes at puberty and is completed at the time of
ovulation
 The second meiotic division takes place over several
hours in the oviduct only after sperm penetration.
TWO DAUGHTER CELLS
 The result is two daughter cells, which are diploid (2N) in
DNA content but contain 23 chromosome structures,
each containing two closely held sister chromatids
o One daughter cell, the oocyte, receives the
majority of the cytoplasm, and the other
becomes the first polar body when ovulation
occurs.
o Both the oocyte and the polar body are
present within the zona pellucida.
MEIOSIS II
 Meiosis II is rapid, and the oocyte advances
immediately to metaphase II
o Where the sister chromatids for each
chromosome are aligned at the equatorial
plate, held together and on the spindle fibers
by the centromere of the chromosome.
IN MALE, meiosis generates four haploid gametes of equal
reproductive potential, whereas in female, only one oocyte is
generated for reproduction.
OOCYTE
 When the egg enters the fallopian tube, it is surrounded
by a cumulus of granulosa cells (cumulus oophorus)
and intimately surrounded by a clear zona pellucida.
 Within the zona pellucida, are both the egg and the
first polar body.
OVARIAN CYCLE, FERTILIZATION, AND HUMAN
DEVELOPMENT DURING THE FIRST WEEK
 STAGE I OF DEVELOPMENT
o Begins with fertilization in the fallopian tube
and ends when the zygote forms.
 STAGE II (Days 2-3)
o Comprises the early stages of cleavage from 2
to about 32 cell, morula
 STAGE III (Days 4-5)
o Consists of the free (unattached) blastocyst
 STAGE IV (Days 5-6)
o Represented by the blastocyst attaching to
the posterior wall of the uterus, the usual site
of implantation
as chemotaxis, which is related to capacitation of the sperm.
 Aided by the binding of progesterone to a surface
receptor on the sperm.
o Allows an increase in ntracellular calcium ion,
which increases sperm motility (chemokinesis)
 Once the sperm has passed the barrier of the zona
pellucida, I attaches to the cell membrane of the egg
and enters the cytoplasm.
 When the sperm enters the cytoplasm, intracytoplasmic
structures, the coronal granules, arranged themselves in
an orderly fashion around the outermost portion of the
cytoplasm just beneath the cytoplasmic membrane,
and the sperm head swells and gives the rise to the
male pronucleus.
*felixthecat
 THE EGG completes its second meiotic division, casting off
the second polar body to a position also beneath the zona
pellucida.
Initially before ovulation, you end up with primary
oocyte. Your dominant follicle out of 1000 primordial follicle will
rupture and then magrerelease sya ng oocyte. And that oocyte
now contains your secondary oocyte, meron syang second
polar body and that will be fertilized. You cannot make use of
the primary oocyte to be fertilized into a zygote. Dapat may
transformation of the primary oocyte to secondary oocyte for
the sperm to fertilize it.
IN VITRO FERTILIZATION
What are doing in the in vitro fertilization? In in vitro,
where the primary oocyte will transform into secondary
oocyte, there will be manipulation of oocytes. That is the
difference of natural and in vitro fertilization process –there
will be manipulation.
 Advances in assisted reproductive technology and
genetics now provide practitioners assess to the
early embryo for preimplantation genetic
diagnosis (PGD) of single-gene or chromosome
disorder
 This technique, involves the removal of one or two
cells at the cleavage stage (six to eight cells) at
day 2 to 4 after fertilization.
 Embryos containing the mutation are discarded
(not transferred), and embryos in which the
mutation in question is not detected are saved.
 PGD must be completed within 12 to 24 hours of
embryo biopsy in order to transfer appropriate
embryos into the uterus.
In a normal fertilization, that sperm must be able to
penetrate the oocyte in order that there will be mixture of
genetic material from the male and female gamete. Though
the next question is who will become the male and who will
become the female out of the fertilized egg? ...depends
again on which one carries the x chromosome and the y
chromosome. All the female’s oocytes, puro x chromosome
carrying. It is the male who will determine whether that
zygote will become a male or a female because it is the
sperm is the one that carries the y chromosome, and also an
x chromosome. So depende kung x or the y chromosome
ang meron kay sperm.
We expect that there will be 4 gametes that will be
produced by the male and there will be 2 gametes that will
be produced by the female. Out of the four gametes in the
male, two of it will be the carrying x, two will be carrying y
chromosome.
After fertilization, there will be cleavage. There will
always be cleavage formation and as you progress with that
we expect that this fertilized egg will be travelling from the
fallopian tube towards the area of the uterine cavity. It will
take only 5 – 6 days for the fertilized egg to be implanted
inside the uterine cavity. That means if you will have your
ovulation today, and you have sex today then count 6 days
from now and you have a positive pregnancy test because
the blastocyst is able to implant itself inside the uterine cavity.
You do not have to wait for 1 week or 2 weeks delay before
you test for your pregnancy. A week after fertilization if there
is implantation, then we expect that your hcg level is
increased.
Stage of implantation:
Formation of zygote  early cleavage (day 2-3 post coitus)
 formation of blastocyst (day 4-5)  implantation (day 5-6)
What will you do if you do not want to get pregnant? Before
time of implantation, dapat na-abort ka na. In case you do not
want to get pregnant, you do not want implantation to occur.
Paano mo di maiimplant yung blastocyst? Destroy the uterine
cavity lining. How? You take contraceptive pills. Instead of 1 tab
of contraceptive pills, you take 3 tablets. So what will happen to
the lining of the endometrium? Maguguluhan yung endometrial
lining. Ano ba to? Iba’t ibang hormones ang nasa katawan ko.
So the lining will be destroyed. In the time of implantation, wala
na makakapitan yung blastocyst. So what will happen to the
blastocyst? It will just pass through the vaginal canal. That
means, no site for implantation.
 CELL DIVISION (cleavage) then occurs, giving rise to the
two celled embryo.
Now always think that the first thing that will happen
between the egg and the sperm after fertilization is the creation
of two cell embryo. We call it now an embryo as early as the
time of fertilization. The big question is when do we consider life?
When do you think if begins? Fertilization or implantation? As you
can observe, as early as fertilization there is now an exchange of
genetic material, there is formation of two cell embryo. Because
if you believe that implantation is the start of life, then you can
always say, pwede pa po tayo magpa-abort before
implantation. Pwede pa po tayong gumawa ng something in
order to prevent implantation and we will not be accused of
abortion. Others will always say, if there is already heart beat
identified by ultrasound, and that is about 6 weeks AOG, then
that is the start of life. So depende po. Depends on your belief.
 The first division takes about 20h to complete, and the
actual phase of fertilization generally occurs in the ampulla
of the fallopian tube.
 A significant number of fertilized ova do not complete
cleavage for a number of reasons
o Failure of appropriate chromosome
arrangement on the spindle
o Specific gene defects that prevent the
formation of the spindle
o Environmental factors
MORULA AND BLASTULA STAGE:
EARLY DIFFERENTIATION
 After the first mitotic division, the cells continue to divide
as the embryo passes along the fallopian tube and
enters the uterus.
 This process takes 3-4 days after fertilization, and the
embryo may arrive at the uterus in any form, from 32
cells to early blastula stage.
 Implantation generally takes place 3 days after the
embryo enters uterus.
*felixthecat
  Implantation depends on the development of early
trophoblastic cells during the blastula stage.
 Trophoblastic cells digest away the zona pellucida and
allow the embryo to fix to the wall of the uterus and
subsequently to burrow within the endometrium.
 The development of the blastula and the separation of
the embryonic disk cells from the developing
trophoblastic cells together make up the first stage of
differentiation in the embryo
 At this stage of development, teratogens are generally
either completely destructive or have little or no effect,
as each of the cells of the early embryonic disk is
pluripotent.
 Differentiation within the embryonic disk, however,
proceeds fairly rapidly, and if separation of cells and
twinning occur at this point, the twins are frequently
conjoined in some fashion.
The presence of your embryonic disk signifies that there
is embryonic development going on. Teratogens, if ever, will be
present during this time before implantation, then you will be
able to see cases of abortions. Kaya yung iba sasabihin, there’s
always ovulation. There’s always coitus. Confounder is no
pregnancy at all because there are teratogens present that
prevents implantation. Bakit yung iba hindi nagkakaanak? Bakit
yung iba normal si babae, normal si lalake and yet bakit hindi
nagkakaanak? And that is because there is teratogens during
the first six days after fertilization.
IMPLANTATION
 Implantation has been noted to occur in the human
embryo as early as day 6 after ovulation.
 For implantation to take place, the zona pellucida must
be removed from the developing blastocyst, which
occurs because of enzyme action produced either by
cells of the blastocyst or by some endometrial enzymes.
 Endometrial capillaries in contact with the invading
syncytiotrophoblast are engulfed to form venous sinuses
at or about 7.5 days after conception and are seen
abundantly by day 9.
 Endometrial spiral arteries are not invaded at this point.
The endoplasmic reticulum of the syncytiotrophoblast is
probably responsible for the synthesis of human
chorionic gonadotropin
o Well developed by 11 days after ovulation.
 Transfer is most likely through the venous sinuses before
intact circulation to the developing embryo has been
established.
What is important after fertilization is always think of
implantation. It is important that that blastocyst must be
implanted inside the uterine cavity ideally. True enough others
will say that if there will be implantation, this is the start of life.
Why? Because according to them, they will always say that that
is the point where there is exchange of maternal and fetal
substances. There will be circulation. But at that point, will you be
alble to justify the division that took place from fertilization to
implantation?
If you will see that there is implantation, ang unang
mag__?__ sa implantation is the syncytiotrophoblast formation.
And that syncytiotrophoblast formation at the time of
implantation will now secrete your hcg, and that hcg will give us
positive pregnancy test. So therefore others claim if the
pregnancy test ay nagpositive na, Then that is the start of life.
In the future when you will become doctors and you
will be ask to offer contraceptive methods of family planning,
either oral, injectables or other devices, you always apply your
belief when you think life will start.
 HCG
 Responsible for maintaining the corpus luteum
 Detected in the peripheral blood of the mother as early
as 6 days after ovulation, but it always is seen by day
12.
 Concentration doubles every 1.2 to 2 days
 Its highest point at 7 to 9 weeks of pregnancy.
The implantation as you can see is accompanied by
the production of hcg.this is one sign that there is already
implantation. It is the one thing that you can observe --- when I
was a student, we do not have ultrasound to check on the
implantation of the blastocyst. What we are relying here, kapag
pinag-pregnancy test ko tong pasyente at nagpositive, then I
can always say that there is already implantation kasi nagkaron
nan g hcg. That was before. But this time, we always look at the
ultrasound. Before, we will always tell ourselves that the
implantation is intrauterine pag may doubling of hcg. Pinagawa
ko na ang hcg titer ngayon, then after 2 days pinagawa ko ulit.
Tinignan ko naging doble ang kanyang hcg, then I will always
say intrauterine ang implantation. If I will see that the hcg hindi
nag-double after 2 days, then I will tell the patient, may possibility
po ectopic ang implantation. So therefore you do rely on these
things. Nowadays, we have a different scenario. Patient will
undergo ultrasound for us to identify nasan ba ang
implantation? Intrauterine or extrauterine? So you now have your
diagnosis. And you will not wait for her to bleed or _____ if it turns
out ectopic. If ectopic, give the injection to dissolve the ectopic
pregnancy. You do not need to do surgery. All you need to do is
give 1 dose of methotrexate and that ectopic surgery will be
dissolved. No surgery need.
EARLY ORGANOGENESIS IN THE EMBRYONIC PERIOD
As you progress with implantation and embryogenesis, there
will be a lot of changes going on even the formation of different
organs, you will be able to observe and ____. Nowadays, we will
be able to say that at this point of embryogenesis, we will see this
development going on.
 During the 3rd week after fertilization, the primitive streak
forms in the caudal portion of the embryonic disk, and
the embryonic disk begins to grow and change from a
circular to a pear-shaped configuration.
 Epithelium facing superiorly is considered ectoderm
o Give rise to the developing central nervous
system
 Epithelium facing downward toward the yolk sac is
endoderm
 The neuroplate develops with its associated
notochordal process
 By the 16th day after conception, the third primitive
germ layer, the intraembryonic mesoderm, begins to
form between the ectoderm and endoderm.
 Early mesoderm migrates cranially, passing on either
side of the notochordal process to meet in front in the
formation of the cardiogenic area.
o Heart soon develops from this area.
 Later in the 3rd week extraembryonic mesoderm joins
with the yolk sac and the developing amnion to
contribute to the developing membranes.
 An intraembryonic mesoderm develops on each side
of the notochord and neural tube to form longitudinal
columns, the paraxial mesoderm.
o Each paraxial column thins laterally into the
lateral plate mesoderm, which is continuous
with the extraembryonic mesoderm of the
yolk sac and the amnion.
*felixthecat
  Angiogenesis can be seen in the extraembryonic
mesoderm of the yok sac by day 15 or 16.
 Embryonic vessels can be seen about 2 days later and
develop when mesenchyme cells known as angioblasts
aggregate to form masses and cords called blood
islands.
 Spaces then appear within these islands, and the
angioblasts arrange themselves around these spaces
to form primitive endothelium.
 The primitive heart forms in a similar manner from
mesenchymal cells in the cardiogenic area.
 Paired endothelial channels, called heart tubes,
develop by the end of the third week and fuse to form
the primitive heart.
 By the 21st day, this primitive heart has linked up with
blood vessels of the embryo, forming a primitive
cardiovascular system.
 Blood circulation starts about this time, and the
cardiovascular system becomes the first functioning
organ system within the embryo.
 All the organ systems form between the 4th and 7th
week AOG.
 A teratogenic event that takes place during the
embryonic period gives rise to a constellation of
malformations related to the organ systems that are
actively developing at that particular time. Thus,
cardiovascular malformations tend to occur because
of teratogenic events early in the embryonic period,
whereas genitourinary abnormalities tend to result from
later events.
 Teratogenic effects before implantation often cause
death but not malformation. If there will be some
exposure to teratogenic materials, what happens to
the zygote? It will abort itself.
 Effects of a particular teratogen depend on the:
o Individual’s genetic make up
o Other environmental factors in play at the
time
o Embryogenic developmental stage during
which the teratogenic exposure occurred
o Dose of teratogen and the duration of
exposure.
 Teratogens may be chemical substances and their by-
products, or they may be physical phenomena, such as
temperature elevation and irradiation.
 Teratogen exposure after the 49th day of gestation may
injure or kill the embryo or cause developmental and
growth retardation but usually will not be responsible for
specific malformation.
During the embryonic period , this is considered as the most
sensitive time of pregnancy. I- expose mo na sya sa radiation
during fetal period but never during the embryonic period
because this is the time where your organs are formed. Pag
nasira mo yung heart development, then congenital anomalies
will be identified.
Your formation of the different primitive parts will be on the
embryonic period. This is considered to be the time most
teratogenic problems are identified. If the patient will be
exposed, at birth lumabas yung bata walang kamay walang
paa. What will you do to pinpoint the diagnosis? You go back to
the history. “Ma’am let me review. Ano po ang mga exposure
ng baby while still in utero during the embryonic period? You
have a thalidomide baby, walang extremities.” So you go back
to the history during the embryonic period. “Ti-nry nyo hu bang
mag-abort? Ti-nry nyo hu bang hindi magbuntis? And what
chemical agent you used?” so sabi nung patient nagtake ako
ng thalidomide. And therefore you have your diagnosis. The
cause is secondary to your thalidomide.
If in case the baby came out mentally abnormal, and if
the parent is alcoholic while the baby is in utero, so what will
happen? Paglabas ng bata parang kulang kulang. You have
your Alcoholic syndrome. So you go back to the history and ask.
Bakt ba nagging ganyan? S it because the family has a history of
mental abnormalities or is it because of the exposure? So you
have to take note of those things.
 The period of embryonic development is said to be
complete when the embryo attains a crown–rump
length of 30 mm
o Corresponding in most cases to day 49 after
conception.
DEVELOPMENT OF THE GENITOURINARY SYSTEM
 The development of the genital organs is intimately
involved with the development of the renal system.
RENAL DEVELOPMENT
 Nephrogenic cords develop from the intermediate
mesoderm as early as the 2-mm embryo stage,
beginning in the more cephalad portions of the
embryo.
 Three sets of excretory ducts and tubules develop
bilaterally.
1. The first, the pronephros, with its pronephric ducts,forms
in the most cranial portion of the embryo at about the
beginning of the fourth week after conception. The
tubules associated with the duct probably have no
excretory function in the human.
 Late in the fourth week, a second set of tubules, the
mesonephric tubules, and their accompanying
mesonephric ducts begin to develop.
o Associated with tufts of capillaries, or
glomeruli,and tubules for excretory purposes
2. Mesonephros functions as a fetal kidney, producing
urine for about 2 or 3 weeks.
 As new tubules develop, those derived from the more
cephalad tubules degenerate.
o 40 mesonephric tubules function on either side
of the embryo at any given time.
3. Metanephros, or permanent kidney, begins its
development early in the fifth week of gestation
a. Starts to function late in the seventh or early in
the eighth week.
 The metanephros develops both from the
metanephrogenic mass of mesoderm, which is the
most caudal portion of the nephrogenic cord, and
from its duct system, which is derived from the
metanephric diverticulum (ureteric bud).
 It is a cranially growing outpouching of the
mesonephric duct close to where it enters the cloaca.
 The metanephric duct system gives rise to:
o Ureter
o Renal pelvis,
o Calyces
o Collecting tubules
 The fetus produces urine throughout all the periods of
gestation, but the placenta handles the excretory
functions of the fetus
 The urine produced by the fetus contributes to the
amniotic fluid.
*felixthecat
  The fetus may swallow the amniotic fluid and
recirculate it through the digestive system.
o An important factor in regulating the amount
of amniotic fluid present in the fetus.
When we talk of genitourinary sytem, always remember
that the kidneys of babies inside the uterus are functioning. Ibig
sabihin, umiihi na yung baby inside. If you will be able to identify
fetuses with oligohydramnios, o kaya anhydramnios, always think
of possibility na hindi umiihi yung bata sa loob because we said
that the urine of the fetus will contribute to the amount of
amniotic fluid. We said that the baby also swallows amniotic fluid
so therefore will be an exchange --- iihi si baby, magus-swallow si
baby so the amniotic fluid will be balanced. Now if there will be
hyper(?), increase in amount of amniotic fluid, think of possibility
hindi nagsuswallow si baby ng amniotic fluid. Ihi lang sya ng ihi.
So you end up with a huge amount of amniotic fluid. There’s
polyhydramnios.
BLADDER AND URETHRA
 The epithelium of the developing bladder is derived
from the endoderm of the vesicourethral canal.
 The muscular layers and serosa of the bladder develop
from adjacent splanchnic mesenchyme.
 The portion of the mesonephric duct distal to the points
where the metanephric duct is taken up into the
bladder becomes the trigone of the bladder.
 The epithelium of the female urethra is derived from
endoderm of the vesicourethral canal.
 The urethral sphincter develops from a mesenchymal
condensation around the urethra after the division of
the cloaca in the 12- to 15-mm embryo.
 Following the opening of the anal membrane at the 20-
to 30-mm stage, the puborectalis muscle appears.
 At 15 weeks’ gestation, striated muscle can be seen,
and a smooth muscle layer thickens at the level of the
developing bladder neck, forming the inner part of the
urethral musculature.
o The urethral sphincter is composed of both
central smooth muscle and peripheral striated
muscle.
 The sphincter develops primarily in the anterior wall of
the urethra in a horseshoe or omega shape.
In the development of the bladder, always think that
the bladder will initially be a storage of your urine.
Ultrasound will tell us whether that bladder is intact or
formed. Because as early as intrauterine, if you do an
ultrasound of the bladder, makikita mo yung bladder
distended with urine. And therefore you can say that you
have a functioning kidney and bladder.
SEX DIFFERENTIATION
How will we determine if this fetus is x carrying or a y
carrying? Then you will always look at the genetic component.
Sometimes what we can do is pwede tayo mag aspirate ng
amniotic fluid, or a part of the placenta and look at the genetic
component. The big question now is can we select the sex of the
baby? There is a capability to choose whether you have an x or
a y by doing your in vitro fertilization. Kung gusto ko yung baby
ko lalake, sasabihin ko dun sa doctor pakibigay yung xy sperm.
Pipili tayo ng xy sperm that will fertilize the egg in vitro.
What we do nowadays if you would like to have a male
child, time your coitus. Ano ibig sabihin? If I would like to have a
male child, I will always do my coitus on my wife’s ovulation day.
Eksakto. Eksaktong nakapag-ovulate na si misis. That means the
egg must be there. Why? Because the x carrying sperm,
mabagal sila. The y carrying sperm are mabibilis. Therefore, if the
egg is already there, nagcoitus sila. Una makakarating sa egg is
the y carrying sperm so mafefertilized kaagad sya. Si x carrying
sperm, mabagal sya. Kaya lang matagal ang buhay. Therefore,
if I would like to have a female child, we will time the coitus
BEFORE ovulation. Why? Because pag dating sperm doon sa
fallopian tube at wala pang itlog, mamamatay na si y carrying
sperm. Ang mabubuhay nalang si x carrying sperm. So pag
dumating is egg sa fallopian tube, puro x carrying sperm nalang
andun.
Always think pag y carrying sperm mabilis kaya lang
mabilis mamatay. The x carrying sperm, mabagal sila kaya lang
matagal ang kanilang buhay.
 Genetic sex is determined at the time of conception.
 A Y chromosome is necessary for the development of
the testes, and the testes are responsible for the
organization of the sexual duct system into a male
configuration and for the suppression of the
paramesonephric (Mu ¨llerian) system.
 In the absence of a Y chromosome or in the absence
of a gonad, development will be female in nature.
 Sex differentiation occurs from genes that are coded
on the Y chromosome. The primary determinant is the
SRY gene, sometimes called the testis-determining
factor.
The presence of the y develops the wolffian duct, the
absence of the y develops the mullerian duct. Yun lang yun.
So it always seem that the y will dictate whether this will
become a male or a female.
 The SRY gene is found on the short arm of the Y
chromosome.
 The SRY gene influences Sertoli cell differentiation,
development of cells in the mesonephric ridge, and
male architectural development of the gonad,
including blood vessels and other structures of the
testes.
 Several other genes, including those that express
steroidogenic factor-1, WT1, DAX1, on other
chromosomes are also necessary for normal testicular
development.
 Male gonadal development precedes female
development. The secretion of testosterone and anti-
Mu ¨llerian hormone (AMH) from the testes steers the
further development of the rest of the genital tracts.
 An interesting bit of evidence for the importance of the
SRY gene in the development of male sexual
differentiation is seen in the 45,X/47,XYY mosaics.
 Hsu postulated that the sex reversal occurred because
of deletion or mutation of the SRY gene.
 Multiple mutations of the SRY gene have been
reported, and all are associated with sex reversals
(female phenotype).
 In very rare male individuals, a Y chromosome may be
absent, but the SRY gene may be located on another
chromosome, most commonly the X chromosome.
 Other rare genetic causes of gonadal dysgenesis may
occur from mutations or deletions in a number of other
genes that influence hormonal and cellular
differentiation.
If ever you will be asked to choose between twins,
sometimes there are those who will say, “Gusto ko po isa
lang ang baby sa loob.” So that means the other one
should be destroyed. So anong gagawin? You have to
choose which sex would you like. The x embryo or the y?
you have to look at the genetic component as soon as 5th
week after pregnancy.
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 During the fifth week after conception, coelomic
epithelium, later known as germinal epithelium, thickens
in the area of the medial aspect of the mesonephros.
 As germinal epithelial cells proliferate, they invade the
underlying mesenchyme, producing a prominence
known as the gonadal ridge.
 In the sixth week the primordial germ cells, which have
formed at about week 4 in the wall of the yolksac,
migrate up the dorsal mesentery of the hindgut and
enter the undifferentiated gonad.
 These cells may differentiate into the testes or ovaries.
 For the formation of a testis, the H-Y antigen must be
activated.
 The somatic cells of the primitive gonadal ridge then
differentiate into interstitial cells (Leydig cells) and
Sertoli cells.
 As they do so, the primordial germ cells and Sertoli cells
become enclosed within seminiferous tubules, and the
interstitial cells remain outside these tubules.
 The HY antigen can be demonstrated in Sertoli cells at
this stage but not in the developing germ cells.
 Sertoli cells are encased in the seminiferous tubules in
the seventh and eighth weeks.
 In the eighth week Leydig cells differentiate and begin
to produce testosterone.
 At this point the mesonephric (Wolffian) duct
differentiates into the vas deferens, epididymis, and
seminal vesicles, while the paramesonephric duct is
suppressed because of the secretion and action of
AMH.
 Androgen action must be initiated at the target areas.
Testosterone enters the cell and either is bound to a
cytoplasmic receptor or, in certain target tissue, is
converted to dihydrotestosterone.
 Dihydrotestosterone in such cells would then bind to a
cytoplasmic receptor.
 Afterward, the androgen-receptor complex gains
access to the nucleus, where it binds to chromatin and
initiates the transcription of messenger ribonucleic acid.
This leads to the metabolic process of androgen action.
 For normal male development in utero, the testes must
differentiate and function normally.
 At a critical point, AMH, produced by Sertoli cells, and
testosterone, secreted by Leydig cells, must be
produced in sufficient amounts.
 AMH acts locally in suppressing the Mu ¨llerian duct
system, and testosterone acts systemically, causing
differentiation of the mesonephric duct system and
affecting male development of the urogenital tubercle,
urogenital sinus, and urogenital folds.
As early as 6th week, you will be able to see the
gonadal formation. The y promotes sertoli cell production,
you have your seminiferous tubules, your sperm production.
You androgen will be dominant if it is a y, and your anti-
mullerian hormones will be increased that inhibits the
mullerian duct development.
 Masculinization of the fetus is a multifactorial process
under a variety of genetic controls.
 Genes on the Y chromosome are responsible for
testicular differentiation.
 Enzymes involved in testosterone biosynthesis and
conversion to dihydrotestosterone are regulated by
genes located on autosomes.
 Development of the ovary occurs at about the
eleventh or twelfth week, though the primordial germ
cells have migrated several weeks earlier to the
germinal ridge.
 Two functional X chromosomes seem necessary for
optimal development of the ovary.
 When non-Y-bearing oocytes enter the differentiating
gonad, the primary sex cords do not become
prominent but, instead, break up and encircle the
oocytes in the cortex of the gonad (in contrast to the
structure of the XY gonad).
 This occurs at about 16 weeks’ gestation, and the
isolated cell clusters derived from the cortical cords
that surround the oocytes are called primordial follicles.
 No new oogonia form after birth, and many of the
oogonia degenerate before birth. Those that remain
grow and become primary follicles to be stimulated
after puberty.
GENITAL DUCT SYSTEM
 The more cephalad ends of the ducts open directly in
to the peritoneal cavity, and the distal ends grow
caudally, fusing in the lower midline to form the
uterovaginal primordium.
o This tubular structure joins the dorsal wall of the
urogenital sinus and produces an elevation,
the Mu ¨llerian tubercle.
 The mesonephric ducts enter the urogenital sinus on
either side of the tubercle.
MALE GENITAL DUCTS
 Some seminiferous tubules are produced in the fetal
testes during the seventh and eighth weeks after
conception.
 During the eighth week, interstitial (Leydig) cells
differentiate and begin to produce testosterone.
 The Mu ¨llerian anlage is suppressed by the action of
AMH,previously called Mu ¨llerian-inhibiting factor (MIF),
produced by the Sertoli cells of the testes.
 The most proximal end of the paramesonephric duct
remains as a small outpouching within the body of the
prostate gland, known as the prostatic utricle.
 Rarely, the prostatic utricle is developed to the point
where it will excrete a small amount of blood and
cause hematuria in adult life.
FEMALE GENITAL DUCTS
 In the presence of ovaries or of gonadal agenesis, the
mesonephric ducts regress, and the paramesonephric
ducts develop into the female genital tract.
o This process begins at about 6 weeks and
proceeds in a cephalad to caudal fashion.
 Failure of development of the paramesonephric ducts
leads to agenesis of the cervix and the uterus
 Failure of fusion of the caudal portion of these ducts
may lead to a variety of uterine anomalies, including
complete duplication of the uterus and cervix or partial
duplication of a variety of types.
 Peritoneal reflections in the area adjacent to the fusion
of the two paramesonephric ducts give rise to the
formation of the broad ligaments.
 Mesenchymal tissue here develops into the
parametrium.
 Pietryga and Wo ´zniak studied the development of
uterine ligaments, documenting the development of
the round ligament at the eighth week, the cardinal
ligaments at the tenth week, and the broad ligament
at week 19.
o From weeks 8 to 17, the round ligament is
connected to the uterine tube.
o Beginning at week 18, it comes to arise from
the edge of the uterus.
*felixthecat
  The vagina develops from paired solid outgrowths of
endoderm of the urogenital sinus— the sinovaginal
bulbs.
 The sinovaginal bulbs then canalize to form the vagina.
o Abnormalities in this process may lead to
either transverse or horizontal vaginal septa.
 The junction of the sinovaginal bulbs with the urogenital
sinus remains as the vaginal plate, which forms the
hymen.
o This remains imperforate until late in
embryonic life, although occasionally,
perforation does not take place completely
(imperforate hymen).
 Failure of the sinovaginal bulbs to form leads to
agenesis of the vagina.
 Auxiliary genital glands in the female form from buds
that grow out of the urethra.
 The buds derive contributions from the surrounding
mesenchyme and form the urethral glands and the
paraurethral glands (Skene glands).
o These glands correspond to the prostate
gland in males.
 Similar outgrowths of the urogenital sinus form the
vestibular glands (Bartholin glands), which are
homologous to the bulbourethral glands in the male.
 The remnants of the mesonephric duct in the female
include a small structure called the appendix
vesiculosa, a few blind tubules in the broad ligaments
(the epoophoron), and a few blind tubules adjacent to
the uterus (collectively called the paroo ¨phoron).
 Remnants of the mesonephric duct system are often
present in the broad ligaments or may be present
adjacent to the uterus and/or the vagina as Gartner
duct cysts. The epoophoron or paroo ¨phoron may
develop into cysts. Cysts of the epoophoron are known
as paraovarian cysts.
 Remnants of the paramesonephric duct in the female
may be seen as a small, blind cystic structure attached
by a pedicle to the distal end of the fallopian tube —
the hydatid of Morgagni.
EXTERNAL GENITALIA
If you will look at the external genitalia on the first few weeks
of gestation you will not be able to differentiate the male and
the female genitalia.it is now common for couples nowadays,
papa-ultrasound sa mall. And the sinologist will say this is a
male/female. Pag nakakita ng scrotum and penis, that is a male.
Pag walang nakita, female. Imagine, walang nakita female
kaagad. May nakita male agad. But what is the scenario
intrauterine? There are females whose clitoris are huge or
enlarged that looks like a penis. Kaya ang magiging problema if
you decide that it is a male and it turned out to be a female,
then the sonologist will have problem with litigation.
 In the fourth week after fertilization, the genital tubercle
develops at the ventral tip of the cloacal membrane.
 Two sets of lateral bodies—the labioscrotal swellings
and urogenital folds—develop soon after on either side
of the cloacal membrane.
 The genital tubercle then elongates to form a phallus in
both males and females.
 By the end of the sixth week, the cloacal membrane is
joined by the urorectal septum.
 The septum separates the cloaca into the urogenital
sinus ventrally and the anal canal and rectum dorsally.
 The point on the cloacal membrane where the
urorectal septum fuses becomes the location of the
perineal body in later development.
 The cloacal membrane is then divided into the ventral
urogenital membrane and the dorsal anal membrane.
 These membranes then rupture,opening the vulva and
the anal canal.
 Failure of the anal membrane to rupture gives rise to an
imperforate anus.
 With the opening of the urogenital membrane, a
urethral groove forms on the undersurface of the
phallus, completing the undifferentiated portion of
external genital development
 Differences between male and female embryos can
be noted as early as the ninth week, but the distinct
final forms are not noted until 12 weeks’ gestation.
 Androgens (testosterone and dihydrotestosterone),
produced by the testes and by peripheral conversion
of testosterone in target cells, respectively, are
responsible for the masculinization of the
undifferentiated external genitalia in males.
 The phallus grows in length to form a penis, and the
urogenital folds are pulled forward to form the lateral
walls of the urethral groove on the undersurface of the
penis.
o These folds then fuse to form the penile
urethra.
 Defects in fusion of various amounts give rise to various
degrees of hypospadias.
 The skin at the distal margin of the penis grows over the
glans to form the prepuce (foreskin).
 The vascular portion of the penis (corpora cavernosa
penis and corpus cavernosum urethrae) arises from the
mesenchymal tissue of the phallus.
 Finally, the labioscrotal swellings grow toward each
other and fuse in the midline to form the scrotum.
 Later in embryonic life, usually at about the twenty-
eighth week, the testes descend through the inguinal
canal guided by the gubernaculum.
 No estrogen receptors have been noted in these
regions, suggesting that maternal estrogen has no
direct influence on male genital development.
 Female external genital structures also contain
androgen receptors, and the distribution of androgen
receptors resembles that of the male.
o This would explain why female genitalia can
be masculinized if exposed to high androgen
levels early in gestation.
Diseases of incomplete or absent masculinization of a male (XY
karyotype) fetus may occur for three reasons:
(1) inadequate or deficient secretion of androgens or
peripheral conversion of testosterone to dihydrotestosterone
(2) absence or deficient receptors
(3) deficient or absent AMH.
 Feminization of the undifferentiated external genitalia
occurs in the absence of androgen stimulation.
 The embryonic phallus does not demonstrate rapid
growth and becomes the clitoris.
 Urogenital folds do not fuse except in front of the anus.
 The unfused urogenital folds form the labia minora.
 The labioscrotal folds fuse posteriorly in the area of the
perineal body but laterally remain as the labia majora.
 Beyond 12 weeks’ gestation, the labioscrotal folds will
not fuse if the fetus is exposed to androgens, though
masculinization may occur in other organs of the
external genitalia.
 The labioscrotal folds fuse anteriorly to form the mons
pubis.
*felixthecat
 It is important for you to take note that if it turned out to
be a female, it is more of the estrogen stimulation.
While if it is a male, it is more of androgen receptor
dominating the external genitalia. There are diseases
that are considered to be incomplete or absent
masculinization or feminization. You have to consider
those factors because there are those who look like a
female but there is a problem in the level of estrogen;
male that has no power to inhibit the mullerian
development.
 The work of Kalloo and coworkers demonstrated that
female external genitalia are intensely estrogen-
receptor-positive compared with the genitalia of the
male.
o These receptors may be seen primarily in the
stroma of the labia minora and in the
periphery of the glans and interprepuce
o The presence of such receptors suggests that
there may be a direct role of maternal
estrogens in the development of female
external genitalia.
o This is in contrast to the long-held belief that
female genital development was passive and
occurred in the absence of androgens.
TAKE NOTE AND READ THE KEYPOINTS. YOUR PLATING EXAMS
WILL BE COMING PURELY HERE. BUT PAGDATING NG LONG
EXAMS, YOU HAVE TO READ THE ENTIRE CHAPTER.
 The ovaries do not descend into the labioscrotal folds.
 A structure similar to the gubernaculum develops in the
inguinal canal, giving rise to the round ligaments, which
suspend the uterus in the adult.
I don’t know if in the future you will be lucky enough to
encounter cases wherein you have problems with
masculinization and feminization to the point you have to
get samples of their tissues and do karyotyping and identify
whether they are really a male or a female. We will always
be looking at the external genitalia as part of identification
of the sexual characteristics. Kaya lang sometimes if you will
be looking at that, there are those cases that feminine
looking ang genitalia but masculine ang kanyang
karyotyping. The question is which one will you take into
consideration: the external genitalia or the genetic
characteristic? It’s always the genetics rather than the
external genitalia.
“There are all these moments you think you won’t survive.
And then you survive.”
-David Levithan
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*felixthecat