Transcript Internal Genital Sex

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“
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
Normal Sexual Determination And Differentiation
Genetic Sex:
Undifferentiated Phase
Gonadal Sex:
Internal Genital Sex:
External Genital Sex:
Differentiation Phase
Genetic Sex
The Gonads Differentiate into testis or
ovaries depends on the presence or
absence of the Y chromosome in the
germ cells.
Normal Sexual Determination And Differentiation
Genetic Sex:
Gonadal Sex:
Undifferentiated Phase
Internal Genital Sex:
External Genital Sex:
Differentiation Phase
(Gonadal Sex)
The Development of the Gonads
The phase of indifferent gonads (Genital Ridge):
By the 6th week the germ cells
(primordial germ cells) migrate to the
genital ridge
the
germ
cells
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.
mesenchymal
stroma (potential
theca/Leydig
cells).
sex cords
(granulosa or
Sertoli cells)
Migratory Path Of Primordial Germ Cells From The Yolk Sac
Along The Hindgut Mesentery, To The Urogenital Ridge At Approximately 5
Weeks
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
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.
Oogonia
(4th month)
(Oogonia)
Germ cell surrounded
by a single layer of
epithelial cells
Primary
Oocytes
1st meiotic
division and
arrest in
prophase
(20th week)
The ovary
contains about 7
million germ cells
Degeneration and
atresia begins
At birth
approximately 2
Million germ
cells remain.
Normal Sexual Determination And Differentiation
Genetic Sex:
Undifferentiated Phase
Gonadal Sex:
Internal Genital Sex:
External Genital Sex:
Differentiation Phase
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.
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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.
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Resorption of the central septum between the
two mullerian ducts.
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.
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.
PD: Paramesonephric duct
MD: Mesonephric Duct
US: Urogenital Sinus
MT: Mullerian Tubrcle
UVP: Uterovaginal primordium
VP: Vaginal plate
Remnants of the mesonephric (wolffian) ducts that may persist in
the anterolateral vagina or adjacent to the uterus within the broad
ligament or mesosalpinx.
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.
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
Differentiation to female phenotype:
In the absence of DHT the bipotential external
genitalia differentiate into female
Indifferent Stage (Approximately 7 weeks)
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“
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.
Anomalies of the external genital organs
Ambiguous Genitalia
Ambiguous Genitalia (Defect of the
clitoris and labia):
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.
Anomalies of the internal genital
tract "Müllerian anomalies"
Obstructive Mullerian Anomalies
Longitudinal Fusion Anomalies
Agenesis/Hypoplasia And Other
Miscellaneous Anomalies
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.
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.
Vaginal atresia
a, Isolated
congenital cervical atresia with normal vaginal
development.
b, Congenital cervical atresia with complete vaginal agenesis
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.
Diagram of hematometra and
hematocolpos with imperforate
distal transverse vaginal septum
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.
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:
Uterine fusion anomalies
A. Normal uterus
Septate uterus
Unicornuate uterus
Bicornuate uterus
Arcuate uterus
Didelphic uterus
with a septate
vagina
Bulging mass in a complete obstructive
longitudinal vaginal septum
Rudimentary horn attached to the unicornuate uterus
with a band of tissue. Dashed lines represent the
dissection planes.
Normal sexual development in embryogenesis consists of
three related sequential processes:]
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.
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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
• 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.