UROGENITAL DEVELOPMENT

& ASSOCIATED ANOMALIES

LEVEL V MBCHB
2018
COMPILED BY EFFIE NAILA
 Learning objectives
 List the genetic and hormonal factors that lead to
sexual differentiation.
 Describe the steps that occur in the differentiation of
the testicles & ovaries
 Explain the formation of the internal and external
genitals of both sexes.
 Name the abnormalities that indicate disorders in the
most important mechanisms of genital development.
 Understand the clinical application of developmental
knowledge of the reproductive system.
 DEVELOPMENT
OF THE URINARY
TRACT
 MALE OR FEMALE
 Sex determination occurs at fertilization.
 The gonads are indifferent up to the 7th week from which
different morphology is evident from the 7 th week.
 The earliest evidence of gonadal development is during
the 5th week.
 The sources of the male & female gonads include:
 Mesothelium (mesodermal epithelium) lining the
posterior abdominal wall
 Underlying mesenchyme
 Primordial germ cells
 Cont.
 By day 21 in the embryonic period, gastrulation
occurs which establishes the 3 definitive germ
layers of the embryo and thus forming a
trilaminar embryonic disk.
 The 3 layers give rise to all tissues & organs
of the adult & they include:
1. Ectoderm
2. Intra – embryonic mesoderm
3. Endoderm
Cont.
 Cont.
 The intermediate mesoderm that temporarily connects
the paraxial & lateral mesoderm differentiates into
urogenital structures. The intermediate mesoderm forms a
urogenital ridge, which is a longitudinal elevation on
either side of the aorta.
 A portion of this ridge forms the nephrogenic cord,
which gives rise to the urinary system. The nephrogenic
cord develops into 3 sets of tubular nephric structures
(from head to tail):
1. The pronephros
2. The mesonephros
3. The metanephros
 Cont.

UROGENIT
AL RIDGE

NEPHROGE
NIC CORD
 1. PRONEPHROS
 The pronephros is the cranial – most & earliest nephric stage.
It appears at 3 weeks of intrauterine life. It develops by
differentiation of intermediate mesoderm cells from the
nephrogenic cord.
 It extends from the 4th to the 14th somite & consists 6 – 10
pairs of tubules.
 These spill into a pair of primary ducts formed at the same
level. These ducts extend caudally & eventually reach & spill
into the cloaca.
 The pronephros is a vestigial structure that disappears
completely by the 4th week of human embryonic life.
 2. MESONEPHROS
 It is located along the mid section of the embryo &
develops by the formation of mesonephric tubules
from intermediate mesoderm.
 It also possesses the mesonephric duct/ Wolffian duct.
 It is the principal excretory organ during early
embryonic life (4 – 8 weeks).
 Many of the mesonephric tubules regress but the
mesonephric duct persists & opens into the cloaca at
the tail of the embryo.
 Parts of the duct system become associated with male
reproductive organs.
 3. METANEPHROS
 This arises caudal to the mesonephros at 5
weeks of development.
 It is derived from the intermediate mesoderm &
develops as an outgrowth of the caudal
mesonephric duct, the ureteric bud & from a
condensation of nearby renogenic intermediate
mesoderm, the metanephric blastema.
 It gives rise to the definitive adult kidney
 STEPS IN RENOGENESIS
 This involves a process of reciprocal induction which is
retinoic acid dependent.
 Cranial – caudal patterning establishes a “renogenic”
region within the intermediate mesoderm in the tail of the
embryo. This renogenic mesoderm is termed the
metanephric blastema.
 The metanephric blastema secretes growth factors that
induce the cranial growth of the ureteric bud from the
caudal portion of the mesonephric/ Wolffian duct into the
dorsal end of the nephrogenic cord, thus getting into
contact with the metanephric blastema which becomes a
cap – like structure over the ampullated end of the bud.
 Cont.
 The ureteric bud proliferates & responds
by secreting growth factors that stimulate
proliferation & then differentiation of the
blastemal cells to form cell clusters which
elongate & differentiate into into glomeruli
& kidney tubules (i.e. induces the
blastema to undergo mesenchymal – to –
epithelial transition).
 Cont.
 The expanded tip of the ureteric bud becomes the
ampulla which subdivides and eventually makes 12 -
15 generations of collecting tubules.
 Dilation of the tubular branches produce the renal
pelvis, the major & the minor calices. The middle
generations form the medullary collecting tubules.
 The cup – shaped end of the metanephric tubule
becomes the Bowman’s capsule. It is invaginated by a
tuft of capillaries forming the glomerulus.
 Cont.
 Formation of urine is thought to
begin at 10 - 13 weeks when 20%
of nephrons are morphologically
mature.
 There are positional changes of
the kidney due to a 90 medial
0

rotation of the kidney.

 Cont.
 Interferences in any aspect of these
inductive events (e.g. mutations of either
the metanephric or ureteric factors or
disruption of retinoic acid signaling) may
cause inhibition of ureteric bud growth
resulting in renal hypoplasia or
agenesis. The converse is true.
Cont.
 Derivatives of:

Metanephric
blastema
Ureteric bud
•Podocytes covering the glomerular
capillaries.
•Collecting tubules
•Epithelial cells lining the Bowman’s
capsule & ducts
•Proximal convoluted tubules
•Descending thick limbs of the loops of •Minor & major
Henle
•Thin limbs of the loops of Henle calyces
•Ascending thick limbs of the loop of Henle
•Distal convoluted tubules •Distal ureter
Summary of
renogenesis
 Examples of disorders in the
differentiation of kidney tissue
Duplication of the urinary tract:
 Occurs when the ureteric bud prematurely divides before penetrating
the metanephric blastema.
 This results in either a double kidney &/or a duplicated ureter & renal
pelvis.
Polycystic kidney disease (PCKD): can arise due to a variety of
factors 
 Loss of polarity: aberrant differentiation of tubule cells resulting in an
inappropriate location of Na+/K+ channels to the apical (rather than
basal) domain of the cells. Na+ is pumped apically, water follows
resulting in dilation of tubule lumens.
 Over – proliferation (gain of function mutations in genes controlling
this): excessive growth of tubule epithelium can occlude the lumen
causing blockage.
 Cont.
Renal – Coloboma syndrome
 The Pax2 gene is essential for metanephric mesenchyme to
differentiate into epithelial tubules in response to inductive
signals from the ureteric bud. Mutations can produce renal
defects. Symptoms in this syndrome include:
 Renal hypoplasia: proliferation of the mesenchyme –
derived – epithelia during development.
 VUR: improper connection of the ureter to the bladder or
inherent defects in epithelial cells in the mature ureter.
 Colobomas (ventral fissures in iris, retina &/or optic nerve):
due to failure of optic fissure to fuse.
 Cont.
Potter sequence is characterized by:
 Oligohydramnios: This is due to in utero renal
agenesis, hypoplasia or dysfunction since amniotic
fluid is produced by the kidneys. amniotic fluid
volume causes pressure on the developing fetus this
results in:
 Sloped forehead
 “Parrot beak” nose
 Shortened fingers
 Hypoplasia of internal organs esp. gut & lungs
Cont.
 Cont.
Nephroblastoma/ Wilms tumor
 This is found in infants from 0 – 24 months of age.
 Consists of blastemal, epithelial & stromal cell
types
 It is associated with mutations in genes related to
kidney development (PAX2, WT1 etc.)
 Essentially due to incomplete mesenchymal – to –
epithelial transformation (i.e. the cells fail to fully
differentiate & they transform into cancerous cells)
ASCENT OF THE KIDNEYS
 The kidneys initially form near the tail of the embryo.
 Vascular buds from the kidneys grow toward and
invade the common iliac arteries.
 Growth of the embryo in length causes the kidneys to
“ascend” to their final position in the lumbar region.
 Rather than “drag” their blood supply with them as
they ascend, the kidneys send out new and slightly
more cranial branches and then induce the regression
of the more caudal branches.
Cont.
Malformations related to the
ascent of the kidneys
 Pelvic kidney (A): one or both kidneys stays in the
pelvis rather than ascending
 Horseshoe kidney (B): the two developing kidneys
fuse ventrally into a single, horseshoe shape that gets
trapped in the abdominal cavity by the inferior
mesenteric artery.
 Supernumerary arteries (C): can often have more
than one renal artery per kidney, which is often
asymptomatic but can sometimes compress the ureter
causing a back flow of fluid into the renal pelvis and
kidney tubules  hydronephrosis.
Cont.
 CLOACA
 At the end of 3rd week, the hindgut is a caudal
diverticulum of the yolk sac into the developing
tail fold. A tubular elongation from the hindgut,
Allantois, extends forward into the
mesenchyme of the body stalk.
 As the embryo grows, the caudal end of the
hindgut enlarges to become an endoderm –
lined chamber, called the cloaca This is a
common chamber into which the gut, allantois
& mesonephric ducts opens.
 Cont.
 The dilated cloaca is in contact with the
ectoderm of the body surface ventral to the
developing tail at the cloacal membrane
 At the beginning of the 4th week a transverse
crescentic fold, the urorectal septum appears
in the wall of the cloaca between the allantois
and hindgut. It grows caudally and ventrally to
divide the common chamber into the urogenital
sinus & the rectum.
 DEVELOPMENT OF THE
BLADDER
 As seen before, the terminal part of the
hindgut ends in the Cloaca, which is an
endoderm – lined chamber that:
 Contacts the surface ectoderm at the
cloacal membrane &
 Communicates with the allantois (a
membranous sac that extends into the
umbilicus alongside the vitelline duct.)
 Cont.
The cloaca is then divided by the urorectal septum into:

A dorsal (inferior) portion that A ventral (superior) portion that

develops into: Rectum & anal develops into:
canal Bladder & urogenital sinus.
Cont.
 Cont.
 At 7 weeks, the septum reaches the cloacal membrane
and the separation of the 2 chambers is completed by
week 8.
 The area of fusion of the urorectal septum and cloacal
membrane is the primitive perineal body.
 As mesoderm proliferates around these membranes
between the ectoderm and endoderm, the urogenital
membrane comes to lie in a groove between two
thickenings, the urogenital folds. The anal membrane
lies at the bottom of the anal pit.
 By the 8th week the urogenital and anal membranes
breakdown and the internal chambers are open to the
exterior.
 Cont.
 As the bladder grows & expands, the distal ends of the
mesonephric ducts are absorbed into the wall of the bladder as
the trigone.
 THE UROGENITAL SINUS
 The undifferentiated stage is composed of 2 parts:
1. Shallow elongated groove lying between the
urogenital fold (phallic portion).
2. Long tubular segment (pelvic portion) that
includes a dilated region. This eventually becomes
the bladder into which the mesonephric duct
opens laterally.
 The phallic portion becomes part of the vestibule in
the female or the penile urethra in male.
 Cont.
 In the males, the pelvic portion does not
change much.
 In the 10th week the urogenital folds fuse
along their edges to enclose the penile urethra.
 In the 12th week epithelial outgrowths around
the entrance of the mesonephric ducts in the
narrow portion of the sinus below the bladder
establish the prostatic anlage.
 Cont.
 In the females, the portion of the pelvic sinus below
the bladder is absorbed into the expanding vestibule
to provide separate openings for vagina and urethra.
 The elongation of the sino – vaginal bulb plays a key
part in establishment of the vagina. This consist of
proliferating tissue from the wall of the urogenital
sinus that contribute to the growing vagina and may
give rise to about 1/3 of lower vagina
 The last remnant of the lower portion of the bulb
tissue develops into the hymen.
 Summary of urogenital sinus
derivatives

 The urogenital sinus will give rise to

the lower urogenital tracts:
 Prostatic & penile urethrae in males
 Urethra & lower vagina in females
Malformations related to the
development of the bladder
 Trigonitis:  As a mesonephric duct derivative, the trigone is
sensitive to sex hormones and can undergo hormone – induced
epithelial metaplasia. This usually involves a transformation
from a transitional type to squamous type epithelium which can
over – proliferate and lead to urinary blockages.
 Abnormal attachment of the ureters: the ureters can
sometimes be attached to either to the urethra or parts of the
reproductive tracts.
 Urachal fistulas, sinuses, and cysts: occur when a remnant
of the allantois persists and are found in the midline along the
path from the umbilicus to the apex of the bladder (i.e. along
the median umbilical ligament).
 DEVELOPMENT OF THE
SUPRARENAL GLANDS
 The adrenal cortex arises mostly from the
intermediate mesoderm in the lumbar region of the
embryo.
 The adrenal medulla arises after trunk neural crest
cells migrate into the center of the adrenal glands &
develop into the chromaffin cells of the adrenal
medulla.
 These cells are essentially postganglionic sympathetic
neurons that release epinephrine or norepinephrine
directly into the bloodstream as opposed to
innervating a target organ.
 DEVELOPMENT OF THE
REPRODUCTIVE SYSTEM
 INTRODUCTION
 The gonads arise from intermediate
mesoderm within the urogenital ridges of the
embryo.
 Gonadal development starts in the 5th & 6th
week of embryonal life in close association with
that of the urinary system.
 Extra – gonadal primordial germ cells migrate
in the 6th week from the wall of the yolk sac
near the allantois into the urogenital ridges.
 Cont.
 They migrate through the mesentery from the
region of the hind gut to the dorsal body wall
and then laterally into the developing gonad on
each side.
 If primordial cells are hindered from reaching
the ridge, gonadal differentiation is incomplete.
The germ cells are the direct ancestors of
spermatozoa and ova in the adult.
 At this stage (7 weeks), they are indifferent but
bi - potential.
 Cont.
 Existing side by side along with the mesonephric duct
system are the paired Wolffian/ Mesonephric &
Müllerian/ Paramesonephric ducts from which the
genital ducts arise as follows:
 Wolffian ducts give rise to male genital ducts.
 Müllerian ducts give female genital ducts.
 External genitalia are undifferentiated & male sexual
differentiation requires the hormonal influence of
Testes Determining Factor (TDF).
 DEVELOPMENT OF THE MALE
REPRODUCTIVE TRACT
 Under the influence of SRY, the gonad develops
into a testis containing spermatogonia, leydig cells,
& sertoli cells.
 Leydig cells produce testosterone, which
supports the growth of the mesonephric ducts.
 NOTE: without testosterone, the
mesonephric ducts will REGRESS.
 The mesonephric ducts develop into the
epididymis & vas deferens
 Cont.
 Some testosterone is converted
into Dihydrotestosterone (DHT), which supports
development of the prostate gland, penis &
scrotum.
 Sertoli cells produce Anti - Müllerian
Hormone, AMH/ Müllerian Inhibiting
Substance, MIS which induces the regression
of the paramesonephric ducts. 
 NOTE: in the absence of MIS, the
paramesonephric ducts will PERSIST.
 DHT mediates:
 Development of the external genitalia & the prostate.
 Growth of facial and body hairs.
 Development of acne and temporal hairline recession.
 Exposure to androgens at critical time periods can lead to
different degrees of masculinization.
 Androgens can superimpose and influence the variable external
ambiguity of the basic female phenotype causing clitoral
hypertrophy, hypospadias and fusion of the labia.
 Insufficient local androgen secretion by the 12th week in the
male will lead to incomplete masculinization of external
genitalia – leading to ambiguity.
 Development of the testis
 Differentiation begins at 7 weeks where spermatogenic
cords develop into seminiferous tubules.
 Week 7: proliferation of tunica albuginea & separation of sex
cords from coelomic epithelium to indicate testicular
development.
 Week 8: Isolation of testicular cords from the germinal
epithelium by the tunica albuginea. The germinal epithelium
regresses to a flat squamous mesothelium.
 The lateral ends of the sex cords develop interconnecting
epithelial strands in proximity with the mesonephric tubules
where the mesonephric glomeruli are regressing. This network
will become the rete testis but will connect at the 12 - 16th
week.
 Cont.
 The testis cords are composed of cells with 2 origins:
1. Primordial germ cells from the allantois 
SPERMATOGONIA
2. Epithelial cells from the coelomic surface of the
gonad (mesothelial cells)  SERTOLI CELLS
 At the 8th week, interstitial cells of Leydig cells are
formed from the mesenchyme surrounding tubules.
Cont.
Descent of the testis
 The testes arise in the lumbar region but then
descend into the pelvic cavity and through the
inguinal canal to end up in the scrotum.
 Descent of the testis is due to tethering of
the testes to the anterior body wall by
the gubernaculum.  With growth and
elongation of the embryo coupled with
shortening of the gubernaculum, the testes are
pulled through the body wall, then the inguinal
canal, and finally into the scrotum.
 Cont.
 Recognition of male fetus
 Regression of primitive mullerian ducts  9th week
 Differential of male external genitalia  10th week
 Testosterone biosynthesis occurs at 9 weeks with
peak levels being reached at 16 weeks
 hCG/LH of syncytiotrophoblast stimulates fetal Leydig
cells to secrete testosterone which is the regulator of
male differentiation of Wolffian ducts, urogenital sinus
and external genitalia
 Summary
 Testicular differentiation is mediated by TDF.
 The 1st endocrine function of the fetal testis is secretion of
AMH (MIS).
 DHT stimulates differentiation of the urethra (?), prostate &
external genitalia whereas, testosterone mediates
differentiation of the Wolffian ducts and associated internal
secondary sex structures.
 Fetal testosterone reaches peak plasma levels at 16 weeks of
gestation.
 hCG & fetal LH are important for continued growth of the penis
& testis during the 2nd and 3rd trimesters.
 Male urogenital tract
derivatives
 Ureteric bud  ureter
 Mesonephric ducts  rete testis, efferent
ducts, epididymis, vas deferens, seminal
vesicle, trigone of bladder
 Urogenital sinus  bladder (except
trigone), prostate gland, bulbourethral
gland, urethra.
 DEVELOPMENT OF THE FEMALE
REPRODUCTIVE TRACT
 In the absence of SRY, the gonad develops into an
ovary with oogonia and stromal cells at 9 weeks.
 Lack of testosterone  mesonephric ducts regress.
 Lack of MIS  paramesonephric ducts persist to
give rise to the oviducts, uterus, cervix & upper 1/3 of
the vagina
 The urogenital sinus contributes to the formation of
the lower 2/3 of the vagina, bulbourethral glands and
the vestibule.
 The paramesonephric ducts
 These are also called the Müllerian ducts. They are of
intermediate mesodermal origin.
 In the male embryo, they degenerate soon after the
7th week, with only the upper & lower extremities
remaining.
 The most cranial portion of the paramesonephric
forms the oviduct. The
 They are paired ducts that run down on the lateral
sides of the urogenital ridge & terminate at the sinus
tubercle in the primitive urogenital sinus.
 Cont.
 In the female they will develop into:
 Fallopian tube  most cranial portion
 Uterus
 Cervix
 Upper third of vagina
 Degenerated cranial portion of the urogenital ridge is
represented by the suspensory ligament of the ovary.
 Caudally, the urogenital ridge swings ventrally & medially to
meet in the mid – line ventral to the hind gut hence forming
the broad ligament.
 The uterine canal
 The uterus is formed by fusion of the caudal,
midline parts of the paramesonephric ducts.
The 2 medial walls of the paramesonephric
ducts fuse into a single wall that eventually
breaks down.
 A unified body is formed by the 10th week of
gestation.
 Resorption of the midline septum occurs by the
20th week of gestation giving rise to the uterus,
cervix & fallopian tubes.
Cont.
 The vagina
 It develops from 2 main sources:
 Upper : lower part of the fused paramesonephric duct (Uterovaginal
canal)
 Lower : sinovaginal bulbs (evagination from the pelvic part of the
urogenital sinus)
 2 solid evaginations (sinovaginal bulbs) form a solid vaginal plate. The plate
develops cranially & is fully canalized by the end of the 5th month (20
weeks).
 The vaginal fornices develop from the paramesonephric duct caudally.
 The lumen of the vagina remains separated from the urogenital sinus by a
thin tissue plate hymen.
 Cont.
 The gonads and reproductive tracts are indifferent up
until 7 weeks of development.
 Differentiation is influenced largely by the presence or
absence or the Testis – Determining Factor, TDF
or the Sex – Determining Region Y, SRY protein.
This is a DNA binding protein encoded by the SRY
gene (on the Y chromosome).
 If SRY is present, then development proceeds along
the male path.
 If SRY is absent, then development proceeds along
the female path.
 Cont.
 In the ovary the sex cords become subdivided
& broken down into irregular groups associated
with some of the primordial germ cells.
 These clusters gradually disappear and the
ovarian medulla of the new – born is essentially
free of these tissue.
 11th – 12th weeks: germ cells in the ovary enter
meiotic prophase with a characteristic transition
of oogonia into primary oocytes which marks
the onset of ovarian differentiation.
 Cont.
 Meiotic division stops at the diplotene stage & the
chromosome enters a resting stage until meiosis I is completed
just before ovulation.
 Some cords persist in the ovarian cortex but eventually
breakdown and the component cells form clusters associated
with primordial germ cells that probably become the oogonia
with the epithelial cells making up the primordial follicles.
 The formation of primordial follicles reaches a maximum at 20
– 25 weeks when the gonad has morphologic characteristics of
a definitive ovary. At birth 1 – 2M germ cells remain
 Cont.
 The retes in the ovary do not become patent or functional.
They may persist as a vestigial epoophoron.
 The mesenchymal substance of the genital ridge inferior to the
gonads terminate caudally in the region of the future external
genitalia  gubernaculum
 In the male, the gubernaculum has a different growth rate
and is involved in testicular descent to the scrotum.
 In the female, the gubernaculum is attached to the fusing
paramesonephric ducts at the angle where they swing
medially to join each other.
 Thus in the female the gonads have a shorter descent as the
gubernaculum is attached at the uterotubal junction
Cont.
 Summary
 In the absence of TDF, gonadal cells have an inherent
tendency to form ovarian – like structures
 In the absence of androgens, an inherent tendency for
formation of female secondary structure exists
 Interstitial steroidogenic cells appear at 12 weeks of
gestation.
 Oogonia formation is complete at 7 months gestation.
 Approx. 2M follicles are present in the newborn ovary
 Primordial follicle development is completed at six
months post – partum.
 Summary of female urogenital
tract derivatives

 Ureteric bud: ureter

 Mesonephric ducts: trigone of bladder
 Paramesonephric ducts: oviduct,
uterus, upper 1/3 of vagina
 Urogenital sinus: bladder (except
trigone), bulbourethral gland, urethra,
lower 2/3 of vagina
 FORMATION OF EXTERNAL
GENITALIA
 External genitalia develop from mesodermal proliferation of 3
masses of tissue between the epidermis and the lower portion
of the urogenital sinus in the triangular region between the
lower limbs and the tail.
 This proliferation of mesoderm & ectoderm around the cloacal
membrane produces 3 masses of primordial tissues of the
external genitalia in both sexes, namely:
1. Median genital tubercle
2. Paired genital folds
3. Paired genital swelling
 The primordia are indistinguishable up until about week 12
 Cont.
 From 4th to 7th week there is proliferation but no differentiation.
 As the mesoderm grows the area of contact between the
epidermis and the epithelium of the urogenital sinus (urogenital
membrane) becomes more deeply buried between the
enlarging folds at each side.
 The membrane then breaks down to open the urogenital sinus
to the exterior.
 The genital folds elongate as a result of growth of the
mesodermal core. Between the 7th & 10th week the genital folds
in the male (urethral folds) begin to fuse and one can now
determine sex orientation by careful inspection.
 Males
 In the male, closure of the urethral folds along the future raphe
converts the elongated phallic portion of the urogenital sinus
into the penile urethra. The genital tubercle becomes canalized
to form the glans by the tunnelling of an epithelial extension of
the urethra established by week 12.
 The prepuce is formed later by an in – growth of a nearly
circular plate of epithelium around the top of the glans.
 The scrotum is formed by enlargement of the genital swellings.
 This is facilitated by the development of processus vaginalis
from the peritoneum in preparation for the later descent of the
testis.
Cont.
 Females
 In the female the genital tubercle (clitoris) is
slowed in growth rate relative to the continuing
expansion of the genital folds and the genital
swellings.
 The genital tubercle becomes buried between
the anterior ends of these structures (folds)
 The genital folds do not fuse and the lower
portion of the urogenital sinus remains open as
the vestibule.
Cont.
 Differentiation of the primordia is
as follows:
GENITAL GENITAL TUBERCLE GENITAL
SWELLING FOLDS
MALE • Scrotum • Body & glans of • Ventral aspect
penis of Penis
• Corpora cavernosum • Penile raphe
& spongiosum
FEMALE • Labia • Body & glans of • Labia minora
majora clitoris
• Mons
Pubis
 Disorders of sex differentiation
Persistent Müllerian Duct syndrome (46, XY)
 This occurs in genetic males with mutations in MIS or in
the MIS receptor.
 Because of testosterone and DHT production, there
are normal male external genitalia and male genital
ducts.
 Because there is effectively NO Mullerian inhibition,
the paramesonephric ducts PERSIST; i.e. there is a small
uterus and paired fallopian tubes.
 The testes may lay either in what would be the normal position
for ovaries (i.e. within the broad ligament) or one or both
testes may descend into the scrotum.
 Cont.
 Androgen insensitivity/ Testicular feminization
syndrome (46, XY)
 This occurs in genetic males with mutations in the
androgen receptor (AR). Lack of virilization is due to the
inability of AR to bind testosterone or DHT.
 XY sex reversal occurs with relatively normal female
external genitalia but undescended testes
 Mesonephric ducts are rudimentary or lacking due to
insensitivity to testosterone signaling.
 Normal production of MIS from Sertoli cells causes Müllerian
duct regression, so no oviducts, uterus, or upper 1/3 of
vagina.
 Cont.
5α-reductase deficiency (46, XY)
 Occurs in genetic males with mutations in 5α-
reductase necessary for the conversion
of testosterone to the more potent
androgen, dihydrotestosterone (DHT).
 External genitalia are partially virilized.
 Mesonephric ducts are intact since they only
require testosterone (which is still present).
 Normal production of MIS from Sertoli cells
causes Paramesonephric duct regression
 Cont.
Masculinized external genitalia due to congenital adrenal
hyperplasia, CAH (46, XX)
 This can present as a DSD in genetic females often due to
defects in 21 - hydroxylase essential for cortisol synthesis. Lack
of feedback to pituitary causes overproduction of ACTH and
over – activity of the adrenal gland.
 Increased production of weak androgenic hormones from the
adrenal gland (can’t make cortisol or aldosterone but can make
androgens such as androstenedione) results in weak
virilization of external genitalia. This may manifest as:
 Enlarged clitoris
 Partial or complete fusion of labia majora
 Cont.
 In this case the internal
genitalia are FEMALE, hence the name
female pseudo - intersexuality.
 Testes absent (no SRY)
 No mesonephric (male) ducts (no
testosterone to support their development)
 NO MIS, so the Müllerian (female) duct
structures (uterus and oviduct) are intact)
 Cont.
 Genetic males (46, XY) can also present with
CAH. 
 However, in these cases, the individuals are
already virilized by testosterone produced by
the testes, so they would not usually also
present with a DSD.
 However, as their adrenal glands cannot make
cortisol and/or aldosterone, they require
immediate hormone replacement therapy.
CONGENITAL ABNORMALITIES
OF THE GENITAL TRACT
 INTRODUCTION
 Uterine malformations are present in 5% of the
population. The incidence among women with unexplained
recurrent miscarriages before 14 weeks is 10 – 23%.
 The incidence is above 25% in women with late abortions
& premature deliveries.
 Gross abnormalities of the uterus and vagina are often
associated with congenital anomalies of the urinary tract
(25% risk)
 It’s thus essential to perform an intravenous pyelogram
on these patients to exclude abnormalities of kidneys and
ureters.
UTEROVAGINAL ANOMALIES
Class 1: Dysgenesis of mullerian duct derivatives
 Features: Agenesis or hypoplasia of mullerian duct derivatives
 Involves uterine tubes, uterus, cervix &/or the upper portion of
the vagina.
 Example: Mayer – Rokitansky – Küster – Hauser (MRKH)
syndrome which has combined agenesis of the uterus, cervix
and upper vagina
Class 2: Disorders of Vertical fusion
 Features: Failed fusion of the müllerian system with the
sinovaginal bulb.
 Examples:
 Cervical dysgenesis
 Transverse vaginal septum (obstructive & non – obstructive)
 Cont.
Class 3: Disorders of lateral fusion
 Features: impaired fusion &/or septal resorption of the fusing
mullerian ducts attempting to form the tubes, uterus, cervix &
upper vagina.
 Results in a duplicated or partially duplicated reproductive
tract.
 Examples:
 Uterus didelphys
 Bicornuate uterus
 Unicornuate uterus
Class 3: Disorders of lateral fusion
 Unusual configuration & combination of defects
 ABNORMALITIES OF THE
VULVA
 Duplication of the vulva: Very rare; mostly an indication of imperfect
twining; also associated with a double vagina & uterus.
 Hyper/ hypotrophy of labia minora: Has the commonest occurrence
of both labia minor and majora anomalies; no treatment is necessary;
simple plastic surgery if necessary.
 Asymmetry of labia minora: Surgical correction can be done where
necessary.
 Ambiguous genitalia
 These occur in CAH, Female & Male Pseudo – hermaphroditism
etc.
 They reveal an enlargement of the phallus labio – scrotal folds
and hypospadic urethra emptying into the urogenital sinus.
 Atresia of labia minora
 Developmental errors of the
cloaca
 Defects in the proper partition of the cloaca
into the hindgut & the urogenital sinus may
result in:
 Persistent cloaca with a common opening for
the bladder, vagina & bowel.
 Fistulae connecting the anus, vagina, rectum
& bladder.
 A perineal, vestibular or vaginal anus
 Imperforate anus.
 Clitoral anomalies
 Hypertrophy of the clitoris
 Splitting or cleavage of the clitoris.
 Usually a part of a major abnormality consisting of bladder
exstrophy/ ectopia vesicae, hypospadia or urethral splitting.
 The anterior portion of the labia majora are widely
separated & when pubic hair appears on the mons pubic, it
is absent along the midline. 
 Bifid clitoris: This can be associated with a defect of the lower
abdominal wall (ectopia vesicae) & a split pelvis
 Agenesis of the clitoris is very rare:
 Vaginal anomalies
Absence
 May be complete or the pouch may be present. It can be associated with
intersex.
 Karyotype:
 XX  appear as normal women
 XY  often normal breast development is scanty; pubic & auxiliary hair
is present with only a vaginal pouch. In this case, it is due to androgen
insensitivity.
 Where cryptomenorrhea/ hematocolpos is present, a plastic surgery
procedure is done to connect the upper vagina & the uterus to the lower
vagina the introitus.
 Creating a vagina for coital purposes should be delayed until the patient
becomes sexually active. A space is dissected between bladder and rectum
and lined with skin graft.
 Cont.
Hypoplasia
 In this case, the vaginal canal is short & narrow with
shallow fornixes & a thin epithelium.
 Cause: absent estrogen stimulus from the ovaries.
 It is always associated with uterine hypoplasia.
 Estrogen therapy is useful
 Other vaginal abnormalities include: congenital
atresia, stricture, septate and sub – septate vagina
 Cont.
Double vagina
 This is rare; May be confused with a septate vagina; in true doubling each
vagina has a separate mucosa, lamina propria & muscular coat. It is often
accompanied by a double vulva, urethra, bladder & uteri.  
Septate Vagina
 Occurs due to failure of proper fusion of the lower portion of the
paramesonephric ducts resulting in a longitudinal sagittal septum that partially or
completely divides the vagina. Often the uterus is bicornuate or separate.
 The cervix is usually single in incomplete vaginal septum, opening into each
halve of the vagina.
 Diagnosis can be coincidental; patients may have dyspareunia esp. when the
septum lies against one side of the vagina or one cavity is much smaller than the
other.
 Treatment is not required but information is necessary. In most cases one side
of the vagina is adequate for normal coitus and delivery.
 Cont.
Transverse vaginal septum
 This is usually due to the failure of canalization of the vaginal
plate.
 Patients present with dyspareunia or diagnosis may be
coincidental during a gynecological examination.
 Cryptomenorrhea/ hematocolpos is present.
 Treatment: vaginal plastic operation to create a vaginal canal
adequate for coitus, elective C\S is indicated in such cases.
Vaginal Hypoplasia
 Usually associated with other urogenital anomalies.
 The vagina may open in the perineum, cloaca – like urogenital
sinus or in the urethra. 
 Cont.
Vaginal Atresia
 This is complete or partial failure of canalization of
vaginal plate.
 Diagnosis is made on an infant during examination at
birth or if the uterus has fully formed, when
menstruation begins. Patients have symptoms like
those of imperforate hymen.
 Treatment: surgical approach both via the abdominal
and vaginal routes.
 Cont.
Vaginal agenesis
 This is due to failure of proliferation of the utero – vaginal plate
 atresia of the vaginal plate.
 Diagnosis is made at birth on examination where no vaginal
opening is seen. In most cases, there is concomitant aplasia of
the upper part of the paramesonephric ducts, thus the uterus &
uterine tubes are rudimentary. The ovaries are, however,
normal (different origin)
 Differentials: Imperforate hymen, Labial adhesion, Large
vaginal cyst, Intersex anomalies  
 Treatment: In the absence of the uterus, the objective is to
create a functionally satisfactory coital canal.
 Cont.
Congenital vaginal cysts
 They usually develop from either of:
 Occluded persistent fragments of the mesonephric
ducts
 Unfused portions of the paramesonephric ducts
 Obstructed para – urethral ducts.
 Treatment is for big ones: Excision (Note that injury to
the urethra, bladder, ureter or bowel may occur)
 ABNORMALITIES OF MÜLLERIAN
DUCT DEVELOPMENT
 These may include:
 Absence or incomplete development of both
müllerian ducts (see classifications)
 Absence or incomplete development of one
müllerian duct: Unicornuate uterus
 Imperfect fusion of the müllerian ducts (This results
in various types of uterus shapes)
 Considering the possibility of obstetric
complications the shape of the cavity is of
greater importance.
 Uterine anomalies
 These rarely present in childhood. They present with
infertility or complications during pregnancy & labor.
Cervical stenosis  rare
Cervical atresia
 Rare
 This is due to failure of development & canalization of
the cervical portion of the fused paramesonephric
ducts.
 May cause hematometra once menarche is reached.
 Cont.
Uterine hypoplasia 
 Lesser degrees of severity are of no consequence but in severe
hypoplasia, the uterus is a small cord of tissue, usually without a
cavity.
 Causes 10 amenorrhea with the ovaries being normal & functional
hence resulting in normal, female sexual characteristics.

Uterine aplasia
 True aplasia is rare .
 In most cases, it is accompanied by aplasia of the uterine tubes.
 Vaginal agenesis is always present in true uterine aplasia.
Failure of para – mesonephric duct
fusion may result in:

 Bicornuate uterus
 Arcuate uterus
 Partially septate uterus
 Unicornuate uterus with rudimentary horn
 Septate uterus with single cervix
 Unicornuate uterus
 Complete septate uterus
Anomalies of the uterine tubes

 These are important in terms of

fertility purposes.
 Example: Small supernumerary or
accessory tubes attached to the
fimbriated ends or communicating
with the isthmus or ampulla portions.
 OVARIAN ANOMALIES
Failure of normal ovarian descent: Remains in the fetal position above the
pelvic inlet.
Ovarian aplasia
 Rare
 Differentials: Undescended testis in a male, inguinal gonads, ovarian torsion
necrosis & resorption
Accessory Ovaries
 Presence of a 3rd ovary lying along the path of ovarian descent.
 Accessory ovarian tissue may exist extra – peritoneally.
Ovarian Hypoplasia
 Poorly developed ovary due to:
 Intersex problem
 Rudimentary gonad (turners)  
Ovarian Agenesis
 COMPLICATIONS IN PATIENTS WITH
MULLERIAN DUCT ABNORMALITIES
 Menstrual symptoms: Cryptomenorrhea, spasmodic dysmenorrhea,
menorrhagia.
 Coital symptoms: dyspareunia, bleeding
 Obstetric complications:
 Uterine rapture in pregnancy & labor 20 to surgical scars for corrective
surgery.
 Twins occupying different horns of the uterus.
 Sacculation of the uterus
 Abortion and preterm labor
 Malpresentation of the fetus
 Obstructed labor
 Inefficient uterine contractions
 Infertility
 Diagnosis
 History
 Examination
 U/S
 HSG
 Laparoscopy
 MRI
 TREATMENT OF PATIENTS WITH
UTERINE ABNORMALITIES

 Depends on the exact state of the deformity and on symptoms

produced.
 Each case requires individual consideration
 Many are best left untreated
 Vagina septa are generally resected
 Rudimentary horns requires excision
 Recurrent abortions in bicornuate uterus requires plastic
operation
 Septum resection can also be done hysteroscopically
 Symmetrical double uterus has an excellent reproductive
performance after surgical unification
 Abnormalities of the hymen
 Firm membranous tissue making normal penetration
impossible.
 Absent hymen
 Anterior displacement
 Hymenal septum: thick median septum creating 2 orifices;
there may be a possibility of a septate vagina & duplication of
internal genitalia.
 Cribriform hymen: may lead to frequent vaginitis
 Almost imperforate hymen
 Imperforate hymen
 Large hymenal orifice
 Imperforate hymen
 Refers to the presence of an imperforate lower transverse
vaginal septum which may lead to hematocolpos during
puberty.
 The imperforate hymen is thought to be a remnant of the
urogenital membrane.
 Imperforate hymen results when the mesoderm of primitive
streak abnormality invades the urogenital portion of the cloacal
membrane.
 Should be drained by cruciate incision under anesthesia.
 This may produce mucocolpos in infancy and hematocolpos
when the girl starts to menstruate.
 Diagnosis
 Infants: may present with abdominal pelvic mass due to
mucoid distension of the vagina displacing the small uterus up-
wards.
 Often diagnosis is made in early adolescence when menstrual
flow fails to appear despite recurrent cyclic menstrual
symptoms, may also present with urinary difficulties, lower
abdominal pain and vaginal discomfort.
 On inspection of vulva: bulging dome – shaped tense hymenal
membrane
 May have: Hematocolpos & hematometra
 Tubes may also be involved.
 Anomalies of the urethra, bladder
and ureter

 Epispadias
 Hypospadias – associated –
incontinence of urine
 Urethral duplication – complete,
partial
 Congenital anomalies of Urethral
Structures
 Relatively Common
 Most of them are found at the external meatus.
Obstruction of the urethra causes distortion of the
urinary tract above.
 May result in: UTI, Hydroureter, Hydronephrosis
 Symptoms – difficult in urinating, bacteriuria, enuresis,
dribbling incontinence, frequent terminal hematuria,
abdominal or flank pain.
 Extreme anomalies may result in loss of renal
function.
 Cont.
 Congenital urethral contractures: Occur at the vesicourethral
juncture; they may have serious consequence if untreated.
 Congenital urethral cysts
 Congenital urethral diverticulum
 Bladder exstrophy
 Urachal anomalies: May present as umbilicovesical fistula or a
urachal cyst. Treatment is by surgical excision.
 Ureteral Ectopy
 Positional anomalies of the ureteral orifices may be formed
“There are more sure marks
of authenticity in the Bible
than in any profane history”
Sir Isaac Newton
(1642 – 1727)