Normal and Abnormal Embryology of the Female Genital Tract

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Normal and Abnormal Embryology of the Female
Genital Tract

• Professor Hassan Nasrat
• Chairman
• Department f Obstetrics and Gynecology
• (Fourth Year Medical Students)

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• Definitions Sexual Determination And sexual
  Differentiation
• Normal Sexual Differentiation
• Differentiation Of The Gonads
• Development Of The Internal Genital System.
• Differentiation Of The External Genital System.
• Abnormal Differentiation
• Anomalies Of The External Genital Organs
• Anomalies Of The Internal Genital Tract
  "Müllerian Anomalies

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Embryology of The Genital Tract (Sexual
determination and Differentiation)

• Sexual determination is related to the Genetic
  Make Up At Fertilization
• Sexual differentiation encompasses the events
  subsequent to gonadal Sex

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Normal Sexual Determination And Differentiation
Genetic Sex
Undifferentiated Phase
Gonadal Sex
Internal Genital Sex
Differentiation Phase
External Genital Sex
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Genetic Sex
The Gonads Differentiate into testis or ovaries
depends on the presence or absence of the Y
chromosome in the germ cells.
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Normal Sexual Determination And Differentiation
Genetic Sex
Gonadal Sex
Undifferentiated Phase
Internal Genital Sex
Differentiation Phase
External Genital Sex
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(Gonadal Sex) The Development of the Gonads
The phase of indifferent gonads (Genital Ridge)
sex cords (granulosa or Sertoli cells)

• By the 6th week the germ cells (primordial germ
  cells) migrate to the genital ridge
• The germ cells influence development of the gonad
  into ovary or testes
• The covering epithelium proliferates and sends
  cluster of cells into the underlying mesoderm
  known as the cells of the sex cords.

the germ cells
mesenchymal stroma (potential theca/Leydig cells).
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Migratory Path Of Primordial Germ Cells From The
Yolk Sac Along The Hindgut Mesentery, To The
Urogenital Ridge At Approximately 5 Weeks
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The phase of Gonadal Differentiation
The differentiation of the gonads into testis
depends on the presence of sex determining region
or gene (SRY) located on the short arm of the Y
chromosome Deletion of this SRY gene results in
XY female. Similarly translocation of this gene
to an X chromosome results in an XX male.
Ovarian Differentiation Occur in the absence of Y
chromosome and SRY protein it occurs two weeks
later (about the 8th week).

• Testis Differentiation

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Ovarian Differentiation
The cortical zone that contain the germ cells
develop to a much greater extent, while the
medulla regress.
(4th month) Each germ cell (Oogonia), is
surrounded by a single layer of epithelial cells
The oogonia are transformed into Primary Oocytes
as they enter the 1st meiotic division and arrest
in prophase until puberty and beginning of
ovulation.
(20th week) The ovary contains about 7 million
germ cells. Degeneration and atresia begins
around 20 weeks and by birth approximately 20,000
germ cells remain.
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Primary Oocytes 1st meiotic division and arrest
in prophase
Oogonia
At birth approximately 2 Million germ cells
remain.
(4th month) (Oogonia) Germ cell surrounded by a
single layer of epithelial cells
(20th week) The ovary contains about 7 million
germ cells Degeneration and atresia begins
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Normal Sexual Determination And Differentiation
Genetic Sex
Undifferentiated Phase
Gonadal Sex
Internal Genital Sex
Differentiation Phase
External Genital Sex
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Normal embryologic processes in development of
the internal female genitalis
(fallopian tubes, uterus, cervix, and the upper
two thirds of the vagina)

• The differentiation of two paired mullerian
  ducts.
• Lateral fusion of the lower segment of the
  mullerian ducts in the midline to form the
  uterus, cervix and upper two third of the vagina.
• Resorption of the central septum between the
  two mullerian ducts.

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Differentiation of the Genital Ducts (The
Internal Genital Organs)
The Indifferent stage

• The Mesonephric (Wolffian) duct run on either
  side of the primitive gut as a longitudinal
  ridge, covered by the coelomic epithelium.
• The Mullerian duct (Paramesonephric ducts)
• Runs lateral to the Mesonephric duct. It
  develops, as a longitudinal invagination of
  coelomic epithelium that runs caudally as a solid
  cord cells.
• At its caudal part the Mullerian ducts pass
  medially across the front of the Wolffian ducts.
• The Mullerian ducts, from each side, meet and
  fuse as a single solid rod of cells.
• They further extend caudally until they make
  contact with the urogenital sinus produce a
  prominent elevation in its posterior wall, known
  as the Mullerian tubercle.

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Stage of Ductal differentiation (8 weeks)
Differentiation of male internal organs - The
Mullerian Inhibiting Hormone (MIH) (Sertoli cells
) responsible for regression of the ipsilateral
paramesonephric ducts - Testosterone (Leydig
cells) responsible for development of the
mesonephric duct into the male internal genitalia

Differentiation of Female Internal Organs
In the absence of testes (MIF and testosterone)
the mesonephric system regress and the Mullerian
duct develop to give the fallopian tube, uterus,
and upper vagina.
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PD Paramesonephric duct MD Mesonephric Duct US
Urogenital Sinus MT Mullerian Tubrcle UVP
Uterovaginal primordium VP Vaginal plate
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Remnants of the mesonephric (wolffian) ducts that
may persist in the anterolateral vagina or
adjacent to the uterus within the broad ligament
or mesosalpinx.
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Development of the External Genitalia
The Phase of undifferentiated external genitalia

• The external genitalia are derived from common
  anlagen
• the genital tubercle, the genital swellings,
  and the genital folds that are capable of
  development into male or female genitalia under
  the influence of androgenic hormones produced by
  the Leydig cells of the testes.

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Differentiation to male phenotype

• The testis begins secretion of testosterone by
  the 8-9th week.
• masculinization of the genitalia is observed
  about a week later (the 10th week) and is
  completed by the 14th week.
• However the target cells of the external
  genitalia must be able to convert testosterone to
  its active product Dihydrotestosterone (DHT)
  under the influence of the intracellular enzyme 5
  alpha reductase

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Differentiation to female phenotype
In the absence of DHT the bipotential external
genitalia differentiate into female
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Indifferent Stage (Approximately 7 weeks)
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Development of the external female genitalia
Approximately 10 weeks Approximately 12 weeks
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• Definitions Sexual Determination And sexual
  Differentiation
• Normal Sexual Differentiation
• Differentiation Of The Gonads
• Development Of The Internal Genital System.
• Differentiation Of The External Genital System.
• Abnormal Differentiation
• Anomalies due to Genetic Factors (Intersex)
• Anomalies Of The External Genital Organs
  (Ambiguous Genitalia)
• Anomalies Of The Internal Genital Tract
  "Müllerian Anomalies

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Abnormalities due to Genetic Factors (Intersex )
Diagram of a G-banded Y chromosome. Y-linked
genes are shown. SHOX/PHOG, short
stature/pseudoautosomal homeobox-containing
osteogenic gene on the X MIC2, a cell-surface
antigen recognized by the monoclonal antibody
12E7 SRY, sexdetermining region Y RPS4Y,
ribosome protein S4Y ZFY, zinc finger Y TSPYA,
TSPYB, testes-specific protein Y PRKY, a member
of the cyclic adenosine monophosphate-dependent
serine threonine protein kinase gene family,
homologous to PRKX. DAZ, deleted in azoospermia
AZF, azoospermific factor.
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Anomalies of the external genital
organsAmbiguous Genitalia

• Ambiguous Genitalia (Defect of the clitoris and
  labia)

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genital deformities seen in female infants who
are masculinized
Sagittal views of A, Minimal masculinization with
slight enlargement of the clitoris. B, Labial
fusion and more marked enlargement of the
clitoris. C, Complete labial fusion, enlargement
of the clitoris, and formation of a partial
penial urethra.
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Anomalies of the internal genital tract
"Müllerian anomalies"

• Obstructive Mullerian Anomalies
• Longitudinal Fusion Anomalies
• Agenesis/Hypoplasia And Other
• Miscellaneous Anomalies

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Obstructive Müllerian anomalies
transverse vaginal septa cervical agenesis
Imperforate hymen (embryo logically not of
mullerian origin)
Patients with this type of anomaly will usually
presents with amenorrhea or Cyclic pain due to
accumulated menstrual flow.
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Potential sites of transverse vaginal septa. A.
High septum. B. Midvaginal septum. C. Low
septum.(From Simpson JL, Verp MS, Plouffe L Jr
Female genital system.
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Vaginal atresia
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a, Isolated congenital cervical atresia with
normal vaginal development.
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b, Congenital cervical atresia with complete
vaginal agenesis
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Imperforate Hymen The hymen represents the
junction of the sinovaginal bulbs with the
urogenital sinus hence it is formed form the
endoderm of the urogenital sinus epithelium.
Clinically
May be discovered at birth ( "mucocolpos or
hydrocolpos"
More commonly at puberty hematocolpos.
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Diagram of hematometra and hematocolpos with
imperforate distal transverse vaginal septum
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Defects of Mullerian Duct fusion

• Unlike obstructive anomalies that usually
  presents with primary amenorrhea, fusion
  anomalies are often associated with gynecological
  as well as obstetrics complications e.g.
  infertility, recurrent pregnancy loss and poor
  obstetrics outcome in pregnancy
• Some case where there is partial obstruction e.g.
  a unilateral rudimentary horn, may present early
  in the years following puberty usually with
  primary cyclic dysmenorrhea.

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Anomalies of lateral fusion of the mullerian
ducts This may be partial or complete failure of
fusion.
Anomalies due to unilateral defects of Mullerian
duct development
Diethylstilbestrol Associated anomalies
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Uterine fusion anomalies
A. Normal uterus
Unicornuate uterus
Arcuate uterus
Didelphic uterus with a septate vagina
Septate uterus
Bicornuate uterus
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Bulging mass in a complete obstructive
longitudinal vaginal septum
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Rudimentary horn attached to the unicornuate
uterus with a band of tissue. Dashed lines
represent the dissection planes.
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• Normal sexual development in embryogenesis
  consists of three related sequential processes
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•    Establishment of chromosomal sex at
  fertilization, with XY as male and XX as female.
  For the first two months of gestation the two
  sexes develop in an identical fashion.  
   Determination of gonadal sex when the
  indifferent gonad develops into an ovary or a
  testis, beginning at week 8.
• .
•     Development of sexual phenotypes as the
  result of gonadal differentiation when the
  indifferent anlagen of the internal and external
  genitalia develop into their characteristic male
  or female structures

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• In females, the müllerian ducts give rise to the
  fallopian tubes, uterus, and upper vagina, and
  the wolffian ducts persist in vestigial form.  
   In males, the wolffian ducts give rise to the
  epididymides, vasa deferentia, seminal vesicles,
  and ejaculatory ducts, and the müllerian ducts
  regress.