DEVELOPMENT OF FEMALE

REPRODUCTIVE SYSTEM
 OUTLINE
• Sex differentiation / determination
• Indifferent gonads
• Clinical application
• Ovary
• Genital ducts
- Indifferent stage.
- Female internal genitalia.
• Vagina
• Uterine and vaginal defects( Clinicals)
• External genitalia
- Indifferent stage.
- Female external genitalia
 Sex Differentiation
• This complex process involves many genes which
include some autosomes.
• Y-chromosome is the key to sexual differentiation
of primordial sexual organs.
• On its short arm resides the SRY gene (sex
determining region on Y-chromosome). The
protein product of the gene is the testis-
determining-factor.
• In its absence, female development is established.
• The genetic sex of the embryo is determined at
the time of fertilization.
 Indifferent Gonads
• Male and female morphological characteristics do
not begin to develop until 7th week.
• The gonads begin as a pair of longitudinal ridges,
the genital or gonadal ridges, by proliferation of
the surface epithelium and condensation of the
underlying mesenchyme on the posterior
abdominal wall.
• Germ cells which originate in the epiblast do not
appear in the ridges until 6th week.
 Indifferent Gonads
• Following gastrulation, the germ cells, by the 3rd
week, reside among the endoderm cells in the
wall of the yolk sack close to the allantois.
• By the 4th week the primordial germ cells migrate
along the dorsal mesentery of the hindgut.
• The germ cells arrive the gonadal ridges at the
beginning of the 5th week.
• They invade the ridges by the 6th week of
development.
 Indifferent Gonads
• The gonads do not develop if the primordial
germ cells fail to reach the genital ridges.
• The epithelium of the genital ridge proliferates
and penetrates the underlying mesenchyme
to form irregularly shaped cords called the
primitive sex cords.
• In the indifferent gonad these primitive sex
cords are connected to the surface epithelium.
Indifferent Gonads
 Clinical Application
• Two X-chromosomes are needed for complete ovarian
development. In embryos with abnormal sex
chromosomes such as XXX or XXY the following are the
outcomes:
• The number of X-chromosome appears to be
unimportant in sex determination.
• With a normal Y-chromosome the embryo develops as
a male.
• In absence of Y-chromosome, the embryo develops as
a female.
• Loss of SRY portion on short arm of the Y-chromosome
leads to female development.
 Clinical Application
• Migration of germ cells to the gonadal ridge is not
affected by loss of an X-chromosome as in 45X0.
• Klinefelter syndrome 47, XXY or 48 XXXY – the most
common major abnormality of sexual differentiation
(1/1500 males). Characterized by infertility,
gynaecomastia, low androgen level and varying
degrees of impaired sexual maturation.
• Gonadal dysgenesis – streak ovaries, absence of
oocytes. Phenotypically female. Variety of
chromosome components may be present. X-Y
female gonadal dysgenesis ( Swyer syndrome) is due
to point mutations or deletion of the SRY gene.
 Development of Ovary.
• This depends on the induction by the primordial germ
cells that invade the indifferent gonad by the 6th
week.
• It occurs in an embryo with XX sex chromosome
complement, absence of SRY gene and presence of
WNT4 gene.
• The primitive sex cords dissociate into irregular cell
clusters containing groups of primordial germ cells
and occupy the inner part of the ovary.
• Normally, they degenerate and disappear and are
replaced by a vascular stroma which forms the
ovarian medulla.
 Development of Ovary

• Unlike in the male gonad, the surface

epithelium of the female gonad continues to
proliferate.
• By the 7th week, the surface epithelium gives
rise to a second generation of sex cords called
cortical cords.
• The cortical cords penetrate the underlying
mesenchyme but still close to the surface.
 Development of Ovary
• By the 3rd month the cortical cords split into
isolated cell clusters, with the cell proliferation
still continuing.
• The cells begin to surround each oogonium with
a layer of epithelial cells now called follicular
cells.
• The follicular cells and the oogonium constitute a
primordial follicle.
• In the female gonad there is failure of the tunica
albuginea to develop.
Development of Ovary
 Descent of the Ovary.
• Descent of the gonads is very much less in the
female.
• The ovaries descend to settle just below the rim of
the true pelvis.
• Gubernaculum, a fibromuscular band of tissue, is
attached to the inferior pole of each gonad.
• As the gubernaculum shortens the ovary is guided
toward the inguinal canal.
 Descent of the Ovary.
• The expansion of the developing uterus traps the
gubernaculum in the wall of the uterus.
• The ovary is then arrested at the level just below
the pelvic brim.
• Ovarian ligament is formed by the part of the
gubernaculum between the ovary and the uterus.
• Round ligament of the ovary, the part of the
gubernaculum that extends from the uterus
through the inguinal canal to the labia majus.
 Indifferent Genital ducts

• Both male and female embryos have two pairs

of indifferent genital ducts: mesonephric
(wolffian ) ducts and paramesonephric
(mullerian) ducts.
• Paramesonephric Duct:
• Arises as a longitudinal invagination of the
epithelium in the anterolateral surface of the
urogenital ridge.
• Opens cranially as a funnel-like structure into
the abdominal cavity.
 Indifferent Genital ducts
• Runs lateral to the mesonepheric duct, then
crosses it ventrally to grow caudo-medially.
• Comes into close contact in the midline with
the duct from the opposite side.
• Caudal tip of the fused ducts projects into the
posterior wall of the urogenital sinus.
• A small swelling, the sinus tubercle results.
Indifferent Genital Ducts
 Female Internal Genitalia
• The recognized parts in each paramesonephric
duct are :
• A cranial vertical part that opens into the
abdominal cavity.
• A horizontal part that crosses the mesonephric
duct.
• A caudal vertical part that fuses with its partner
from the opposite side.
• With the descent of ovary the main female
internal genitalia are formed by the
paramesonephric duct as follows:
 Female Internal Genitalia.
• Uterine tube, from the first two parts above.
• Uterine canal – the epithelium of the corpus & cervix
of the uterus and the upper part of the vagina –
formed by the fused caudal vertical part of the
paramesonephric ducts.
• Myometrium & perimetrium(peritoneal cover) –
formed by the mesenchyme surrounding the uterine
canal.
• The broad ligament is formed by a broad transverse
pelvic fold extending from the lateral sides of the
fused paramesonephric ducts.
Female Internal Genitalia
 Development of the Vagina.
• Dual origin; the uterine canal and urogenital sinus.
• The upper portion, from the uterine canal.

• Sinovaginal bulbs, two solid evaginations, grow out

from the pelvic part of the urogenital sinus shortly
after contact with the fused paramesonephric ducts.
• Solid vaginal plate is formed by the sinovaginal bulbs
as they proliferate.
• The cranial end of the vaginal plate continues to
proliferate thereby increasing the distance between
the uterus and the urogenital sinus.
 Development of the Vagina
• The vaginal plate is fully canalized by the 5th month
of development.
• The vaginal fornices are formed by the wing-like
expansions of the vagina around the end of the
uterus.
• Hymen – a thin tissue plate consisting of the
epithelial lining of the urogenital sinus and a thin
layer of vaginal cells separates the vaginal lumen
from that of the urogenital sinus.
 Genital Ducts in the Female++CHECK

• In the female sexual development does not

depend on the presence of ovaries or
hormones.
• The paramesonephric ducts develop because
of the absence of mullerian inhibitory
substance even in a genetic male. The
paramesonephric ducts form most of the
female genital tract.
 Uterine and Vaginal Defects

• Lack of fusion of the paramesonephric ducts

results in a number of uterine defects.
• Uterus didelphys – double uterus, no fusion
of the ducts; associated with double vagina.
• Uterus bicornis- uterus with two horns with
one vagina.
• Uterus bicornis unicollis – a rudimentary horn
with one cervix.
 Uterine and Vaginal Defects
• Uterus arcuate- uterus with slight projection
into the cavity.
• Double vagina –a rise from failure of fusion of
the sinvoaginal bulbs.
• Vaginal atresia –due to failure of development
of sinovaginal bulbs.
• Mayer-Rokitansky-Kuster –Hauser syndrome:
absence of the vagina and uterus
 Vestigial Structures from Embryonic
Genital Ducts
Female
• Epoophoron – remnants of the cranial
mesonephric (excretory) tubules in mesovarian.
• Paroophoron – remnants of the caudal excretory
(mesonephric) tubules in the meso-ovarian.
• Gartners duct/cyst – remnants of caudal portion of
the mesonephric duct found in the wall of the
uterus or vagina (the portion corresponds to vas
deferens and ejaculatory duct).
 External Genitalia - Indifferent Stage

• The hindgut terminates temporarily at an ectodermal-

endodermal membrane called the cloacal membrane.
• By 3rd week, mesenchyme cells from the region of the
primitive streak form a pair of slightly elevated swellings
around the cloacal membrane – the cloacal folds.
• Cranially, cloacal folds unite to form the genital tubercle.
• Fusion of urorectal septum divides the caudal part of the
cloacal folds into urethral folds (urogenital) and anal
folds.
 External Genitalia - Indifferent Stage
• Genital swellings, another pair of elevations,
form on each side of the urethral folds.
• The external genitalia are sexually
undifferentiated (indifferent stage) up to early
7th week of development.
• They are fully differentiated by the 12th week.
External Genitalia – Indifferent Stage
 External Genitalia in the Female.

• It is unclear what the controlling factors are in

the development of female external genitalia.
• Oestrogens are, however, known to have a role.
• The genital tubercle elongates slightly to form
the clitoris.
• The genital tubercle in female is larger than in
male during the early stages of development.
• The urethral folds develop into the labia minora
 External Genitalia in the Female
• The genital swellings enlarge to form the labia
majora.
• The urogenital groove bounded by the urethral folds
remain open and forms the vestibule
• The frenulum of the labia minora is formed by fusion
of the urethral folds posteriorly.
• The genital swellings fuse anteriorly to form the
mons pubis and anterior labial commissure.
• They fuse posteriorly to form posterior labial
commissure.
External Genitalia in the Female