Transcript Anomalies of the internal genital tract

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 differentiation
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Abnormalities that might affect normal differentiation of the
female genital tract.
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Clinical complication and presentation of abnormal
differentiation of the female genital tract.
Development of the Internal genital system (Duct system
differentiation)
External Genital differentiation:
Anomalies of the external genital organs:
Anomalies of the internal genital tract "Müllerian anomalies“
Complications and Clinical Presentations of internal genital
tract "Müllerian anomalies“
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The mechanism of normal sexual determination and differentiation
Genetic Sex
Gonadal Sex
Internal Genital Sex
External Genital Sex
Each of the three major elements of the genital tract goes through two
phases:
a Bipotential phase (undifferentiated phase)
Differentiation phase into either a male or female organs.
Embryology of The Genital Tract
(Mechanism of sexual determination and
differentiation)
Sexual determination: is related to the
development of the primary gonad (or
gonadal sex)
Sexual differentiation: encompasses the
events subsequent to gonadal Sex
(Gonadal Sex)
The Development of the Gonads
The phase of indifferent gonads (Genital Ridge):
The germ cells (primordial germ cells)
migrate to the genital ridge by the 6th
week.
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 three elements of the
gonads which are still
"indifferent" are now
completed; the germ cells,
the cells of the sex cords
(the potential granulosa or
Sertoli cells), and the
mesenchymal stroma
(potential theca/Leydig
cells).
The phase of The phase of Gonadal Determination
Differentiate into testis or ovaries depending on the presence or absence
of the Y chromosome in the germ cells.
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 the absence
of Y chromosome and
SRY protein
it occurs two weeks later
(about the 8th week).
Testis Differentiation
• Seminephrous tubules:
proliferation of primitive
sex cords
• The tunic albuginea The
cortical region (the surface)
of the testis
• The epididymis made by
the Mesonephric tubule
The cortical zone that contain the germ cells develop to a much greater
extent, while the medulla regress.
By the fourth month:
each germ cell, now become known as 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.
Around the 20th week of gestation the ovary contains about 7 million germ cells
(see chapter on ovulation).
Degeneration and atresia begins around 20 weeks and by birth approximately 20
million germ cells remain.
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.
Development of the External
Genitalia:
The Phase of undifferentiated external genitalia
Unlike the internal genitalia where there are
two duct systems one for male and one for
female, 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
Migratory Path Of Primordial Germ Cells From The Yolk Sac
Along The Hindgut Mesentery, To The Urogenital Ridge At Approximately 5
Weeks
Indifferent Stage (Approximately 7 weeks)
Development of
the external
female genitalia
Approximately 10 weeks
Approximately 12 weeks
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.
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.
Rudimentary horn attached to the unicornuate uterus without
intervening tissue. Dashed lines represent dissection planes.
a, Isolated congenital cervical atresia with normal vaginal development.
b, Congenital cervical atresia with complete vaginal agenesis
Isolated congenital cervical atresia with normal vaginal
development. b, Congenital cervical atresia with complete vaginal
agenesis
Vaginal atresia.(From Sarto GE, Simpson JL: Abnormalities of
müllerian and wolffian duct systems. Birth Defects: Original Article
Series 14(6a):37, 1978.)
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. In Stevenson RE, Hall JG, Goodman RM [eds]: Human
Malformations and Related Anomalies, vol 11, pp 563–588. New York: Oxford
University Press, 1993.)
Anomalies of the external genital organs
Ambiguous Genitalia
Ambiguous Genitalia (Defect of the
clitoris and labia):
Anomalies of the internal genital
tract "Müllerian anomalies"
Normal development of the internal female
genitalis (fallopian tubes, uterus, cervix, and the
upper two thirds of the vagina) depends on three
consecutive embryologic processes; first the
differentiation of two paired mullerian ducts,
second, 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
and finally resorption of the central septum
between the two mullerian ducts in order to form
a single uterine cavity and cervix.
In this classification four classes of Mullerian
anomalies are identified; the two major ones are;
disorders that compromise patency of the
reproductive tract (obstructive mullerian
anomalies) and disorders of lateral fusin of
patent reproductive tract (longitudinal fusion
anomalies). The remaining two classes are
agenesis/hypoplasia (as in AFS class 1) and
other miscellaneous anomalies that are difficult
to classify
Obstructive Müllerian anomalies
transverse vaginal septa and cervical agenesis and dysgenesis with or
without obstruction. Imperforate hymen is embryologically not of
mullerian origin although clinically have a similar presentation.
Patients with this type of anomaly will usually presents with
amenorrhea or pain due to accumulated menstrual flow.
b) 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.
An imperforate hymen may be discovered at birth because of the presence of a supr
More commonly however an imperforate hymen remains undetected until pubert
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 such as 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: