Development of the Female

Reproductive System
 objectives
 To describe the development of the gonadal
system, noting the differences in
developmental fates of reproductive
primordia;
 To describe the development of the duct
system in females;
 To describe the development of external
genitalia;
 Describe the embryological basis of congenital
anomalies of the reproductive system.
Development of genital system
 Genetic sex is established at
fertilization by the kind of sperm
that fertilizes the ovum
 The gonads begin to attain
sexual characteristics from 7th
week.
 Early genital systems in two
sexes are similar; this initial
period is called indifferent state
of sexual development
Genital System
 Gonads (primitive sex
glands)
İndifferent stage
 Genital ducts
 External genitalia
Development of ovaries

 The mesothelium
(mesodermal
epithelium) lining the
posterior abdominal wall
 The underlying
mesenchyme
(intermediate
mesoderm)
 The primordial germ
cells
 Indifferent gonads

 During the 5th week a

thickened area of
mesothelium develops on the
medial side of the
mesonephros: a pair of
gonadal(genital) ridges
 Finger-like epithelial cords
(gonadal/primitive sex cords)
grow into the underlying
mesenchyme
 The indifferent gonad now
consists of an external cortex
and an internal medulla.
 If the embryo is XX: cortex
will differentiate into an
ovary, medulla regress
 Primordial germ cells

 The large spherical

primordial germ cells
originate from endodermal
cells of the yolk sac
 The primordial germ cells
migrate along the dorsal
mesentery of the hindgut to
the gonadal ridges
 During 6th week primordial
germ cells enter the
underlying mesenchyme and
are incorporated in the
gonadal cords.
Development of ovaries

 Gonadal development occurs slowly in female

 In XX embryo primitive sex cords dissociate into irregular cell
clusters containing groups of primitive germ cells in the medullary
part of ovary
 Later they disappear and are replaced by a vascular stroma that
forms the ovarian medulla
Development of ovaries

 Surface epithelium of the

female gonad continues to
proliferate giving rise to a
second generation of cortical
cords in the 7th week.
 Cortical cords penetrate the
underlying mesenchyme but
remain close to the surface
 In the 4th month cortical cords
split into isolated cell clusters
with each surrounding one or
more primitive germ cells
 Germ cells develop into
oogonia,
 surrounding epithelial cells,
descendants of the surface
epithelium form follicular cells.
 Development of genital ducts: Indifferent
stage

 At the begining both male and female embryos have 2 pairs of genital ducts:
 Mesonephric (wolffian) ducts
 Paramesonephric (mülerian) ducts arising as a longitudinal invagination of
the epithelium on the anterior surface of the urogenital ridge
 Two ducts are separated by a septum but later fuse to form the uterine canal
 The caudal tip of the combined ducts projects into the posterior wall of the
urogenital sinus causing a swelling (paramesonephric/müllerian tubercle)
 The mesonephric ducts open into the urogenital sinus an either side of the
müllerian tubercle
Development of genital ducts:
Indifferent stage

7th week
9th week
 Molecular regulation of female genital
duct development

WNT4
 WNT4 is the ovary determining gene;
upregulating DAX1 which is a member of
the nuclear hormone receptor family
 DAX1 inhibits the function of SOX9
 WNT regulates expression of other genes DAX1 Other genes
(TAFII105....TATA binding protein for RNA TAFII 105
polimerase in ovarian follicular cells)
responsible for ovarian differentiation
 *Mice that do not synthesize that subunit
do not form ovaries
 Estrogens are involved in sexual
differentiation; under their influence Ovaries
paramesonephric (mullerian) ducts are
stimulated to form oviducts, uterus, cervix
and upper 1/3 of vagina
 Genital duct development in
female

 Paramesonephric ducts
develop into the main genital
ducts
 Initially 3 parts can be
recognized in each duct:
 Cranial vertical portion that
opens into the abdominal
cavity....develop into uterine
tube
 Horizontal part that crosses the
mesonephric duct...develop
into the uterine tube
 Caudal vertical part that fuses
with its partner from the
opposite side...fuse to form
uterine canal
Genital duct development in female

 When the paramesonephric ducts fuse in the midline; a broad transverse

pelvic fold (broad ligament of uterus) is established.
 The uterine tube lies in its upper border and the ovary lies on its posterior
surface
 Uterus and broad ligs divide the pelvic cavity into uterorectal pouch and the
uterovesical pouch
 Fused paramesonephric ducts differentiate into corpus and cervix of the
uterus.
 They are surrounded by a layer of mesenchyme (intermediate mesoderm)
that forms the myometrium and the perimetrium
Early development of uterus and the
ovaries
Development of the vagina

 After the solid tip of the

paramesonephric ducts reaches
the urogenital sinus; two solid
evaginations (sinovaginal
bulbs) grow out from the pelvic
part of the sinus.
 Sinovaginal bulbs proliferate
and form a solid vaginal plate.
 Proliferation continues at the
cranial end of the plate;
increasing the distance
between the uterus and the
urogenital sinus.
 By the 5th month vaginal
outgrowth is entirely canalized.
Vaginal fornices (wing-like
expansions of the vagina
around the end of uterus) are
of paramesonephric origin
Development of vagina

 The vagina has two origins:

 upper portion derived from
the uterine canal
 lower portion derived from
the urogenital sinus
 Lumen of the vagina
remains separated from
that of the urogenital sinus
by a thin tissue plate; the
hymen
 Hymen consists of epithelial
lining of the sinus and a
thin layer of vaginal cells. It
usualy develops an opening
during perinatal life
 Remnants of the ducts in female
 Remnants of the cranial and
caudal excretory tubules in the
mesovarium form the
epoophoron and paroophoron
respectively
 Mesonephric duct disappear
except for a small cranial
portion found in the
epoophoron and a small
caudal portion in the wall of
uterus or vagina (Gartner’s
cyst)
 Congenital anomalies of uterus and
vagina
 Double uterus (uterus didelphys): results from failure of fusion of
the inferior parts of the paramesonephric ducts. It may be
associated with double or single vagina.
 Bicornuate uterus: One paramesonephric duct is retarded in its
growth and does not fuse with other one.
 Bicornuate uterus with rudimentary horn: the rudimentary horn may
not communicate with uterine cavity
 Unicornuate uterus: One paramesonephric duct fails to develop;
resulting in a uterus with one uterine tube.
 Absence of vagina and uterus: Results from the failure of
sinovaginal bulbs to develop.
 Vaginal atresia: Failure of the canalization of the vaginal plate.
 Imperforate hymen: Failure of perforation of the inferior end of the
vaginal plate
Uterine anomalies

A. Normal uterus and

vagina
B. Double uterus
C. Double uterus with single
vagina
D. Bicornuate uterus
E. Bicornuate uterus with a
rudimentary left horn
F. Septate uterus
G. Unicornuate uterus
Congenital anomalies of
hymen
 Development of external genitalia: indifferent
stage

 In the 3th week mesenchyme

cells originating in the region of
the primitive streak migrate
around the cloacal membrane to
make a pair of slightly elevated
cloacal folds.
 Cranial to the cloacal membrane,
the folds unite to form the
genital tubercle
 Caudally the folds are subdivided
into urethral folds anteriorly and
anal folds posteriorly
 Another pair of elevations
(genital swellings) becomes
visible on each side of the
urethral folds
 Later these swellings form the
labioscrotal swellings
Development of external genitalia in female

 Stimulated by estrogens, genital tubercle elongates only slightly

forming the clitoris
 Urethral folds do not fuse; develop into labia minora
 Genital swellings enlarge and form the labia majora
 Urogenital groove is open and forms the vestibule
 Although the genital tubercle does not elongate extensively
in female, its larger than in male during the early stages;
resulting in mistakes in identification of the sex by
ultrasound examination.
5th week
Development of external genitalia

A-B: 4th-7th week

İndifferent stage

C, D: 9th week
E, F: 11th week
G, H: 12th week
 Descent of the ovaries

 Descent is considerably less in

female
 The ovaries settle below the
rim of the true pelvis
 Cranial genital ligament forms
the suspensory ligament of
ovary
 Caudal genital ligament forms
the ligament of the ovary
proper and the round ligament
of the uterus
Sex determination
 Female phenotype requires two X chromosomes with a number of
genes
 Absence of a Y chromosome (XX sex chrom) results in the formation
of the ovary
 Types of present gonads determines the type of sexual differentiation
of the genital ducts and external genitalia.
 Testosterone produced by the fetal testes determines maleness.
 Primary female sexual differentiation does not depend on hormones;
occurs even if the ovaries are absent (depending possibly on an
autosomal gene)
Abnormal sex chromosome complexes

 XXX, XXY
 Number of X chromosome appears to be unimportant in
sex determination
 If a normal Y chromosome is present the embryo
develops as a male. If Y chromosome or its testis
determining region is absent female development occurs
Turner syndrome (45X)
Congenital malformations:Determination of fetal
sex

 Ambiguous genitalia: if there is normal sexual differentiation, int

and ext genitalia are consistent with the chromosome
complement
 True hermaphroditism: having ovarian and testicular tissue
either in the same or opposite gonads (70 % are 46 XX, 20 %
46 XX/46 XY mosaicism, 10 % 46XY)
 Female pseudohermaphroditism: 46 XX, having ovaries,
resulting from the exposure from excessive androgens of female
fetus. Virilization of ext genitalia occurs. Common cause is
congenital adrenal hyperplasia, rare cause may be maternal
masculinizing tumor.
 Male pseudohermaphroditism: 46XY having testis, with no sex
chromatin. Int and ext genitalia are varible caused by
inadequate production of testosterone and MIF by testes.
Female pseudohermaphroditism (caused by
congenital adrenal hyperplasia)
Congenital malformations:Determination of fetal
sex
 Androgen insensitivity syndrome (testicular feminization): Normal
appearing females with the presence of testes and 46XY chromosomes.
 They are medically and legally female.
 There is resistance to the action fo testosterone at the cellular receptor
 Mixed gonadal dysgenesis: very rare, having chromatin negative nuclei
(sex chromatin negative), a testis on one side, an undifferentiated
gonad on the other side.
 The int genitalia are female, but may have male derivatives.
 The ext genitalia may vary from female to male.
Androgen insensitivity syndrome
(testicular feminization):46XY
Cogito ergo sum!... I think therefore I am!