Download The Mullerian duct (Paramesonephric ducts)

Fifth stage
‫براء‬.‫د‬
Gynecology
Lec-
Embryology of the Female Genital Tract
 An understanding of the development and anatomy of the female genital tract is
important in the practice of gynecology.
 Both the urinary and genital systems develop from a common mesodermal ridge
running along the posterior abdominal wall.
 It is important to remember that congenital anomalies of the genital tract may also
be associated with congenital anomalies of the urinary tract.

Following fertilization the normal embryo contains 23 sets of chromosomes
,including 22 autosomes and one sex chromosomes from each parent.

46XY embryo will develop as a male

46XX embryo will develop as a female

It’s the presence or the absence of the Y chromosome which determines whether
the undifferentiated gonad becomes a testis or an ovary.
 Y chromosome contains the SRY (sex-determining region on Y) gene on its short arm.
The protein product of this gene is a transcription factor that initiates a cascade of
downstream genes that determine the fate of primordia of the sexual organs.
 The SRY protein is the testis-determining factor; its presence influences the male
development, while its absence establishes the female development.
 Although genetic sex is determined at fertilization, the early genital system is
indistinguishable between the two sexes in the embryonic stage. This is known as the
“indifferent stage” of genital development, during which both male and female
fetuses have gonads with prominent cortical and medullary regions, dual sets of
genital ducts, and external genitalia that appear similar.
 By the 6th week embryonic life, both male and female embryos start to develop the
following structures on either side of the midline:
1. Genital ridge (proliferation of coelomic epithelium)
2. Mesonephric (Wolffian) duct (lateral to the genital ridge)
3. Paramesonephric (Mullerian) duct
1
 Clinically, sex is not apparent until about the twelfth week of embryonic life and
depends on the elaboration of testis determining factor and, subsequently,
androgens by the male gonad.

Female development has been called the “basic developmental path of the human
embryo,” requiring not estrogen but the absence of testosterone.
 Normal Sexual Determination And Differentiation:-
 The Gonads:Gonads:The phase of indifferent gonads (Genital Ridge): o The gonads do not acquire male or female morphological features until
the 7th week of development.
2
o The primitive gonad appears in embryos at around 5 weeks’ gestation. At
this time coelomic epithelium develops on the medial aspect of the
urogenital ridge and following proliferation leads to the establishment of
the gonadal ridge (a pair of longitudinal ridges lie ventro-medial to the
mesonephric kidney. These are epithelium covered condensations of
mesenchyme).
o Epithelial cords then grow into the mesenchyme (primary sex cords) and
the gonad now possesses an outer cortex and an inner medulla. In
embryos with an XX complement, the cortex differentiates to become the
ovary and the medulla regresses.
o The primordial germ cells develop by the 4th week in the endodermal cells
of the yolk sac and during the 5th week they migrate along the dorsal
mesentery of the hindgut to the gonadal ridges, eventually becoming
incorporated into the mesenchyme and the primary sex cords by the end
of the 6th gestational week. If they fail to reach the ridges, the gonads do
not develop.
o It is impossible to differentiate between the male and the female gonad.
Hence the gonad is known as the indifferent gonad.
—
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.
 Ovarian Differentiation
 Occur in the absence of Y chromosome and SRY protein
 it occurs two weeks later (about the 8th week).
3
 Testis Differentiation
 sex determining region or gene (SRY)
 Male sex determination in the absence
 of a Y chromosome results in XX sex reversed individuals.
 There are two main types, SRY positive XX males and
 SRY negative XX males and the majority are SRY positive
 with the SRY gene being located on the X chromosome
 Ovary: If no Y chromosome is present, the gonad, by default, forms an ovary; the
cortex develops, the medulla regresses, and oogonia begin to develop
within follicles. The surface epithelium give rise to a second generation of
cords, the cortical cords (secondary sex cords). These cords will split into
cell clusters, each holding a primitive germ cell. Germ cell develop into
oocyte and surrounding cord cells become a single layer of flat cells, the
follicular cells & whole structure as the primordial follicle.
 An interesting feature of the formation
 of follicles and the development of stroma is the
 disintegration of those oocytes which do not succeed in encircling
themselves with a capsule of pregranulosa cells.
4
5
 The oogonia are derived from the primitive germ cells by a series of about 30
mitoses, for fewer than the number required for spermatogenesis. Beginning at
about the end of the third month, the oogonia enter meiosis I, but this this process is
arrested at a stage called dictyotene, in which the cell remains until ovulation occurs
many years later.
 The number of oocytes is greatest during pregnancy and thereafter declines. It is
found that the total population of germ cells rose from 600,000 at 2 months to a
peak of 7 million at 5 months. At birth the number falls to 2 million, of which half are
atretic.
 The internal genital system:Genital Ducts: Indifferent Stage
o Both male and female embryos start with two pairs of genital ducts: the mesonephric
ducts and paramesonephric ducts.
6
o The Mesonephric (Wolffian) duct: run on either side of the primitive gut as a
longitudinal ridge, covered by the coelomic epithelium.
o The Mullerian duct (Paramesonephric ducts):
o Runs lateral to the Mesonephric duct.
o At its caudal part the Mullerian ducts pass medially across the front of the Wolffian
ducts.
o 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 (sinusal
tubercle).
Genital Ducts (6th Week):-
7
 Molecular Regulation of Genital Duct Development
o Male sex determination is controlled by the SRY gene, the testis determining factor
on the Y chromosome.
o SRY gene product act as a transcription factor that induces expression of downstream
genes leading to production of Mullerian inhibiting substance (MIS), and testosterone
.
 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
8
 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.
The paramesonephric (mullerian) duct:
o The coelomic epithelium lateral to the Wolffian duct is invaginated to form the
Mullerian duct which grows caudally, at first it is solid, but later it becomes canalized
o It deviates more and more medially till it meets its fellow of the opposite side .
o The septum between the 2 Mullerian ducts disappear . The proximal parts of the
Mullerian ducts form the fallopian tubes , while the distal parts meet together to
form the body and cervix of the uterus and the upper 4/5 th of the vagina . The
stroma and muscles develop from the surrounding mesoderm .
Genital Ducts in Female
A(After 8th week), B(After descent of Ovary)
9
– Remnants of the mesonephric (wolffian) ducts that may persist in the
anterolateral vagina or adjacent to the uterus within the broad ligament or
mesosalpinx.
 Vagina:o The Mullerian ducts reach down to the urogenital sinus and at the meeting point ,
form the Mullerian tubercle which meet a pair of endodermal sinovaginal bulbs
which arise from the urogenital sinus .
o These evaginations, the sinovaginal bulbs, proliferate and form a solid vaginal plate.
o By the 5th month, the vaginal plate is entirely canalized to form vagina.
o The lumen of the vagina remains seperated from the urogenital sinus by a thin tissue
plate, the hymen, which consists of the epithelial lining of the sinus and a thin layer
of the vaginal cells. It usually develops a small opening during perinatal life.
10
 Development of the External Genitalia::The Phase of undifferentiated external genitalia
--There is a common indifferent stage consisting of two genital folds, two genital
swellings and a midline anterior genital tubercle.
 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
11
 Clitoris develops from the genital tubercle (by slight elongation)
 Labia minora develop from the genital folds (by remaining separate)
 Labia majora develop from the genital swellings (by enlarging greatly)
 Vestibule develops from the lower most part of the urogenital sinus.

Summary of Normal Sex Differentiation:-
o The SRY gene directs the gonad to become a testis.
o The absence of the SRY gene allows the gonad to become an ovary.
o The presence or absence of androgen determines external genital development.
o The presence of gonadal testosterone production leads to Wolffian duct
differentiation into vas deferens, epidydmus and seminal vesicle.
o The presence of gonadal AMH production leads to Mullerian duct regression.
o The absence of gonadal AMH production allows Mullerian duct differentiation into
upper vagina, cervix,uterine gland and epithelium and fallopian tubes.
o The absence of gonadal testosterone production allows Wolffian duct regression.
12
13
14