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UROGENITAL SYSTEM
A. SUNUSI
21/03/2024 1
INTRODUCTION
• Urogenital system comprise the urinary and genital system functionally.
• However anatomically and embryologically they are interwoven.
• The urogenital system develops from the intermediate mesenchyme derived
from the dorsal body wall of the embryo.
• During folding of the embryo in the horizontal plane, this mesoderm is carried
ventrally and loses its connection with the somites.
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• A longitudinal elevation of mesoderm-the urogenital ridge-forms on each side
of the dorsal aorta.
• The part of the urogenital ridge giving rise to the urinary system is the
nephrogenic cord the part giving rise to the genital system is the gonadal ridge.
• The following genes are important for the formation of the urogenital ridge:
Wilms' tumor suppressor 1 (WT1), steroidogenic factor 1, and DAX1 gene,
mutations of which result in X-linked adrenal hypoplasia congenita.
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Development of urinary system
The urinary system begins to develop before the genital system and consists of:
• The kidneys: excrete urine
• The ureters: convey urine from the kidneys to the urinary bladder
• The urinary bladder: stores urine temporarily
• The urethra: carries urine from the bladder to the exterior of the body
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Development of the kidney
• Three sets of kidneys develop in human embryos.
• The first set-the pronephroi-is rudimentary, and the structures are never
functional.
• It occur in the cervical region early in the fourth week.
• It soon degenerate but the length of it duct persist
• The second set-the mesonephroi-is well developed and functions briefly.
• It appears late in the fourth week caudal to pronephroi
• It consist of glomerular and tubule
• The third set-the metanephroi-becomes the permanent kidneys.
• It begins to develop early in the 5th weeks and start functioning approximately 4
weeks later.
• Urine formation continues throughout foetal life, excreted into the amniotic
cavity and mixed with amniotic fluid.
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Development of Permanent Kidney
• Permanent kidney develop from two sources:
1. The metanephric diverticulum (ureteric bud)
2. The metanephrogenic blastema or metanephric mass of mesenchyme
• The metanephric diverticulum is an outgrowth from the mesonephric duct near
its entrance into the cloaca.
• the metanephrogenic blastema is derived from the caudal part of the
nephrogenic cord.
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1. The metanephric diverticulum
elongates to penetrate the
metanephrogenic blastema-a mass
of mesenchyme.
2. The stalk of the metanephric
diverticulum becomes the ureter.
3. The cranial portion of the
diverticulum undergoes repetitive
branching, forming the branches
which differentiate into the
collecting tubules of the
metanephros.
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Figure: Development of the permanent kidney. A, Lateral view of a 5-week embryo showing the primordium of
the metanephros. B to E, Successive stages in the development of the metanephric diverticulum (fifth to eighth weeks).
* Note: the development of the ureter, renal pelvis, calices, and collecting tubules.
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• The first four generations of tubules enlarge and become confluent to form the
major calices.
• The second four generations coalesce to form the minor calices.
• The end of each arched collecting tubule induces clusters of mesenchymal cells in
the metanephrogenic blastema to form small metanephric vesicles.
• These vesicles elongate and become metanephric tubules.
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• The proximal ends of these tubules are invaginated by glomeruli.
• The tubules differentiate into proximal and distal convoluted tubules, and the
nephron loop (Henle loop), together with the glomerulus and its capsule,
constitute a nephron.
• Each distal convoluted tubule contacts an arched collecting tubule, and the
tubules become confluent.
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• The number of glomeruli increases gradually b/w the 10th and 18th weeks of
gestation, until the 32nd week.
• The fetal kidneys are subdivided into lobes.
• The lobulation usually disappears during infancy as the nephrons increase and
grow.
• Each kidney contains 400,000 to 2,000,000 nephrons on complete growth.
• The increase in kidney size after birth results mainly from the elongation of the
proximal convoluted tubules as well as an increase of interstitial tissue.
• Nephron formation is complete at birth except in premature infants.
• Glomerular filtration begins at approximately the ninth foetal week.
• Functional maturation of the kidneys and increasing rates of filtration occur after
birth.
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Uriniferous Tubules
• Consist of two embryological different parts:
1. A nephron, from metanephrogenic blastema.
2. A collecting tubule derived from metanephric diverticulum (ureteric bud)
• Branching of the metanephric diverticulum is dependent on induction by the
metanephric mesenchyme.
• Differentiation of the nephrons depends on induction by the collecting tubules.
• The metanephric diverticulum and the metanephrogenic blastema interact and
induce each other, a process known as reciprocal induction, to form the
permanent kidneys.
• Transformation of the metanephric mesenchyme to the epithelial cells of the
nephron-mesenchymal-epithelial transition-is regulated by mesenchyme factors
including Wnt4.
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Figure: A to D, Diagrammatic ventral views of the abdominopelvic region of embryos and fetuses (sixth to ninth weeks) showing
medial rotation and relocation of the kidneys from the pelvis to the abdomen. A and B, Observe also the size regression of the
mesonephroi. C and D, Note that as the kidneys relocate, they are supplied by arteries at successively higher levels and that the
hilum of the kidney is eventually directed anteromedially.
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Changes in Position of the Kidney
• Initially the metanephric kidneys (primordial permanent kidneys) lie close to each
other in the pelvis, ventral to the sacrum.
• As the abdomen and pelvis grow, the kidneys gradually come to lie in the
abdomen and move farther apart.
• They attain their adult position by the ninth week.
• The ascent results mainly from the growth of the embryo's body caudal to the
kidneys.
• Initially the hilum of the kidney faces ventrally; however, as the kidney relocates
(ascends), it rotates medially almost 90 degrees.
• By the ninth week, the hilum is directed anteromedially.
• Eventually the kidneys become retroperitoneal (external to the peritoneum) on
the posterior abdominal wall.
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Clinical correlation
• Unilateral renal agenesis occurs approximately once in every 1000 newborn
infants.
• Males are affected more often than females, and the left kidney is usually the
one that is absent.
• It causes no symptoms because the other kidney undergoes compensatory
hypertrophy and performs the function of the missing kidney.
• Unilateral renal agenesis should be suspected in infants with a single umbilical
artery.
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Bilateral renal agenesis is associated with oligohydramnios (small amount of
amniotic fluid) because little or no urine is excreted into the amniotic cavity.
• It occurs approximately once in 3000 births, and is incompatible with postnatal
life because of the associated pulmonary hypoplasia.
• These infants have a characteristic facial appearance: the eyes are widely
separated and have epicanthic folds, the ears are low-set, the nose is broad and
flat, the chin is receding, and there are limb defects.
• Most infants with bilateral renal agenesis die shortly after birth or during the first
months of life.
• Renal agenesis results when the metanephric diverticula fail to develop or the
primordia of the ureters degenerate.
• Renal agenesis probably has a multifactorial etiology.
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• Malrotated kidney: If a kidney fails to rotate, the hilum faces anteriorly, that is,
the fetal kidney retains its embryonic position.
• If the hilum faces posteriorly, rotation of the kidney proceeded too far.
• If it faces laterally, lateral instead of medial rotation occurred.
• Abnormal rotation of the kidneys is often associated with ectopic kidneys.
• Ectopic kidney: Abnormal position, ectopic kidneys are located in the pelvis, but
some lie in the inferior part of the abdomen.
• Pelvic kidneys and other forms of ectopia result from failure of the kidneys to
alter position during embryo growth.
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• Pelvic kidneys are close to each other and may fuse to form a discoid
("pancake").
• Ectopic kidneys receive their blood supply from blood vessels near them (internal
or external iliac arteries and/or aorta).
• Sometimes a kidney crosses to the other side, resulting in crossed renal ectopia
with or without fusion.
• An unusual type of abnormal kidney is unilateral fused kidney. In such cases, the
developing kidneys fuse while they are in the pelvis, and one kidney attains its
normal position, carrying the other kidney with it.
• Horseshoe kidney: In 0.2% of the population, the poles of the kidneys are fused;
usually the inferior poles fuse and lies in the hypogastrium, anterior to the
inferior lumbar vertebrae.
• Normal ascent of these fused kidneys is prevented because they are caught by
the root of the inferior mesenteric artery.
• It usually produces no symptoms because its collecting system develops normally
and the ureters enter the bladder.
• Approximately 7% of persons with Turner's syndrome have horseshoe kidneys.
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Development of the Urethra
• The epithelium of most of the male urethra and the entire female urethra is
derived from endoderm of the urogenital sinus
• In males, the distal part of the urethra in the glans of the penis is derived from a
solid cord of ectodermal cells that grows inward from the tip of the glans and
joins the rest of the spongy urethra.
• The epithelium of the terminal part of the urethra is derived from the surface
ectoderm.
• The connective tissue and smooth muscle of the urethra in both sexes are
derived from splanchnic mesenchyme.
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Development of Urinary Bladder
• the urorectal septum divides the cloaca into a dorsal rectum and a ventral
urogenital sinus.
• For ease the urogenital sinus is divided into three parts : A cranial, vesical part
that forms most of the bladder and is continuous with the allantois
• A middle, pelvic part that becomes the urethra in the bladder neck, the prostatic
part of the urethra in males, and the entire urethra in females
• A caudal, phallic part that grows toward the genital tubercle (primordium of the
penis or clitoris)
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• The bladder develops mainly from the vesical part of the urogenital sinus, but
its trigone region is derived from the caudal ends of the mesonephric ducts.
• The entire epithelium of the bladder is derived from the endoderm of the
vesical part. The other layers of its wall develop from adjacent splanchnic
mesenchyme.
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Development of suprarenal gland
• The cortex and medulla of the suprarenal (adrenal) glands have different origins.
• The cortex develops from mesenchyme
• The medulla differentiates from neural crest cells.
Figure: Schematic drawings illustrating development of the suprarenal glands. A, At 6 weeks, showing the mesodermal
primordium of the fetal cortex. B, At 7 weeks, showing the addition of neural crest cells. C, At 8 weeks, showing the fetal cortex
and the early permanent cortex beginning to encapsulate the medulla. D and E, Later stages of encapsulation of the medulla by
the cortex. F, Newborn infant showing the fetal cortex and two zones of the permanent cortex. G, At 1 year, the fetal cortex has
almost disappeared. H, At 4 years, showing the adult pattern of cortical zones. Note that the fetal cortex has disappeared and
that the gland is much smaller than it was at birth (F).
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• The zona fasciculata is derived from transitional zone b/w permanent and fetal
cortex.
• The zona glomerulosa and zona fasciculata are present at birth.
• The zona reticularis is not recognizable until the end of the third year.
• The suprarenal glands of the human fetus are 10 to 20 times larger than in the
adult.
• Largeness of the suprarenal glands result from the extensive size of the fetal
cortex, which produces steroid precursors that are used by the placenta for the
synthesis of estrogen.
• The suprarenal medulla remains relatively small until after birth.
• The suprarenal glands rapidly become smaller as the fetal cortex regresses during
the first year of infancy.
• The glands lose approximately one third of their weight during the first 2 or 3
weeks after birth and do not regain their original weight until the end of the
second year.
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• During the sixth week, the cortex begins as an aggregation of mesenchymal cells
on each side of the embryo between the root of the dorsal mesentery and the
developing gonad
• The cells that form the medulla are derived from an adjacent sympathetic
ganglion, which is derived from neural crest cells.
• Initially the neural crest cells form a mass on the medial side of the embryonic
cortex.
• As they are surrounded by the cortex, these cells differentiate into the secretory
cells of the suprarenal medulla.
• Later, more mesenchymal cells arise from the mesothelium and enclose the
cortex. These cells give rise to the permanent cortex.
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Clinical correlation of suprarenal gland
• Congenital Adrenal Hyperplasia and Adrenogenital Syndrome
• An abnormal increase in the cells of the suprarenal cortex results in excessive
androgen production during the fetal period.
• In females, this usually causes masculinization of the external genitalia.
• Affected male infants have normal external genitalia, and the syndrome may go
undetected in early infancy.
• Later in childhood in both sexes, androgen excess leads to rapid growth and
accelerated skeletal maturation.
• The adrenogenital syndrome associated with congenital adrenal hyperplasia
(CAH) manifests itself in various forms that can be correlated with enzymatic
deficiencies of cortisol biosynthesis.
• CAH is a group of autosomal recessive disorders that result in virilization of
female fetuses.
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• CAH is caused by a genetically determined mutation in the cytochrome P450c21-
steroid 21-hydroxylase gene, which causes a deficiency of suprarenal cortical
enzymes that are necessary for the biosynthesis of various steroid hormones.
• The reduced hormone output results in an increased release of
adrenocorticotropin from the anterior pituitary, which causes CAH and
overproduction of androgens.
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DEVELOPMENT OF THE GENITAL SYSTEM
• The early genital systems in the two sexes are similar; therefore, the initial period
of genital development is referred to as the indifferent stage of sexual
development.
• Morphological features of both sex start to manifest in the seventh week.
• Development of the Gonads
• The gonads: testes and ovaries are derived from three sources:
• Mesothelium (mesodermal epithelium) lining the posterior abdominal wall
• Underlying mesenchyme (embryonic connective tissue)
• Primordial germ cells
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Indifferent stage
• The initial stages of gonadal development occur during the fifth week when a
thickened area of mesothelium develops on the medial side of the mesonephros.
• Proliferation of this epithelium and the underlying mesenchyme produces a
bulge on the medial side of the mesonephros-the gonadal ridge.
• Finger like epithelial cords-the gonadal cords-soon grow into the underlying
mesenchyme.
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• The indifferent gonad now consists of an external cortex and an internal
medulla.
• In embryos with an XX sex chromosome complex, the cortex of the indifferent
gonad differentiates into an ovary, and the medulla regresses.
• In embryos with an XY sex chromosome complex, the medulla differentiates
into a testis, and the cortex regresses, except for vestigial remnants.
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Primordial germ cells
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They are large and spherical
Are visible early in the fourth week in the endodermal cells of the umbilical
vesicle (yolk sac near the origin of the allantois).
The primordial germ cells migrate along the dorsal
mesentery of the hindgut to the gonadal ridges.
During the sixth week, the primordial germ cells enter the underlying
mesenchyme and are incorporated in the gonadal cords.
The migration of the primordial germ cells is regulated
by the genes stella, fragilis, and BMP-4.
Sex determination
• Depends on whether an X-bearing sperm or a Y-bearing sperm fertilizes the X-
bearing oocyte.
• Before the seventh week, the gonads of the two sexes are identical in
appearance and are called indifferent gonads .
• Development of the male phenotype requires a Y chromosome.
• The SRY gene for a testis-determining factor (TDF) has been localized in the sex-
determining, short arm region of the Y chromosome.
• It is the TDF regulated by the Y chromosome that determines testicular
differentiation.
• The gonadal cords differentiate into seminiferous cords (primordia of
seminiferous tubules).
• Expression of the Sox9 and Fgf9 genes is involved in the formation of the
seminiferous cords.
• The absence of a Y chromosome results in the formation of an ovary.
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• Two X chromosomes are required for the development of the female phenotype.
• A number of genes and regions of the X chromosome have special roles in sex
determination.
• The type of gonads present then determines the type of sexual differentiation
that occurs in the genital ducts and external genitalia.
• Testosterone, produced by the fetal testes, dihydrotestosterone, a metabolite of
testosterone, and the antimullerian hormone (AMH), determines normal male
sexual differentiation.
• Primary female sexual differentiation in the fetus does not depend on hormones.
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Development of testes
• The SRY gene for TDF on the short arm of the Y chromosome controls the
development of the indifferent gonad into a testis.
• Expression of the transcription factor SOX9 is also essential for testicular
determination.
• TDF induces the gonadal cords to condense and extend into the medulla of the
indifferent gonad, where they branch and anastomose to form the rete testis.
• The connection of the gonadal cords-seminiferous cords-with the surface
epithelium is lost when a thick fibrous capsule, the tunica albuginea, develops.
• The development of the dense tunica albuginea is the characteristic feature of
testicular development.
• Gradually the enlarging testis separates from the degenerating mesonephros and
becomes suspended by its own mesentery, the mesorchium.
• The seminiferous cords develop into the seminiferous tubules, tubuli recti, and
rete testis.
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Schematic illustrations showing differentiation of
the indifferent gonads of a 5-week embryo (top)
into ovaries or testes. The left side of the drawing
shows the development of testes resulting from
the effects of the testis-determining factor (TDF)
located on the Y chromosome.
Note that the gonadal cords become seminiferous
cords, the primordia of the seminiferous tubules.
The parts of the gonadal cords that enter the medulla
of the testis form the rete testis. In the section of the
testis at the bottom left, observe that there are two
kinds of cells, spermatogonia, derived from the
primordial germ cells, and sustentacular or Sertoli cells,
derived from mesenchyme. The right side shows the
development of ovaries in the absence of TDF.
Cortical cords have extended from the surface epithelium
of the gonad and primordial germ cells have entered
them. They are the primordia of the oogonia.
Follicular cells are derived from the surface epithelium
of the ovary.
• The seminiferous tubules are separated by mesenchyme that gives rise to the
interstitial cells (Leydig cells).
• By the eighth week, these cells begin to secrete androgenic hormones-
testosterone and androstenedione, which induce masculine differentiation of
the mesonephric ducts and the external genitalia.
• Testosterone production is stimulated by human chorionic gonadotropin, which
reaches peak amounts during the 8- to 12-week period.
• In addition to testosterone, the fetal testes produce a glycoprotein, AMH, or
mullerian-inhibiting substance (MIS).
• AMH is produced by the sustentacular cells (Sertoli cells), which continues to
puberty, after which the levels of AMH decrease.
• AMH suppresses development of the paramesonephric ducts, which form the
uterus and uterine tubes.
•
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• The seminiferous tubules remain solid (i.e., no lumina) until puberty, at which
time lumina begin to develop.
• The walls of the seminiferous tubules are composed of two kinds of cells Sertoli
cells, supporting cells derived from the surface epithelium of the testis
• Spermatogonia, primordial sperm cells derived from the primordial germ cells
• Sertoli cells constitute most of the seminiferous epithelium in the fetal testis.
• During later fetal development, the surface epithelium of the testis flattens to
form the mesothelium on the external surface of the adult testis.
• The rete testis becomes continuous with 15 to 20 mesonephric tubules that
become efferent ductules (Latin, ductuli efferentes).
• These ductules are connected with the mesonephric duct, which becomes the
duct of the epididymis
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Development of ovaries
• Gonadal development occur slowly in female fetus
• X-chromosome and autosomal chromosome play a role in this ovarian organogenesis
• The ovary is not identifiable histologically until approximately 10th week
• The gonadal cord do not become prominent but extend into the medulla and form
rudimentary rete ovarii which usually degenerate and disappear with the gonadal
cord.
• The cortical cord extends from the surface epithelium of the developing ovary into
underlying mesenchyme
• As the cortical cord increase in size, primordia germ cells are incorporated in them
• At approximately 16 weeks, these cords begin to break up into isolated cell clusters-
primordial follicles- consists of an oogonium, derived from a primordial germ cell,
surrounded by a single layer of flattened follicular cells derived from the surface
epithelium.
• Active mitosis of oogonia occurs during fetal life producing primordial follicles
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Development of ovaries cont…
• No oogonia is form postnatally.
• Many oogonia degenerate b/4 birth, about 2 million enlarge and form the
primary oocyte b/4 birth.
• After birth, epithelium of the ovary flatten into a single layer of cell which
continuous with the mesothelium of the peritonium at the hilum of the ovary.
• The surface epithelium becomes separated from the follicles in the cortex by a
thin fibrous capsule, the tunica albuginea.
• As the ovary separates from the regressing mesonephros, it is suspended by a
mesentery-the mesovarium.
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• The mesonephric ducts (Wolffian ducts) play an important part in the
development of the male reproductive system
• Paramesonephric ducts (mullerian ducts) have a leading role in the
development of the female reproductive system.
• The paramesonephric ducts develop lateral to the gonads and mesonephric
ducts on each side from longitudinal invaginations of the mesothelium on the
lateral aspects of the mesonephroi.
• The edges of these paramesonephric grooves approach each other and fuse to
form the paramesonephric ducts.
• The funnel-shaped cranial ends of these ducts open into the peritoneal cavity.
• Caudally, the paramesonephric ducts run parallel to the mesonephric ducts
until they reach the future pelvic region of the embryo.
• Here they cross ventral to the mesonephric ducts, approach each other in the
median plane, and fuse to form a Y-shaped uterovaginal primordium .
• This tubular structure projects into the dorsal wall of the urogenital sinus and
produce an elevation: sinus tubercle.
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Development of male genital ducts and glands
• The fetal testes produce masculinizing hormones (e.g., testosterone) and MIS.
• The Sertoli cells begin to produce MIS at 6 to 7 weeks.
• The interstitial cells begin producing testosterone in the eighth week.
• Testosterone, production is stimulated by human chorionic gonadotropin, stimulates
the mesonephric ducts to form male genital ducts, whereas MIS causes the
paramesonephric ducts to disappear by epithelial-mesenchymal transformation.
• Under the influence of testosterone produced by the fetal testes in the eighth week,
the proximal part of each mesonephric duct becomes highly convoluted to form the
epididymis.
• As the mesonephros degenerates, some mesonephric tubules persist and are
transformed into efferent ductules.
• These ductules open into the duct of the epididymis (Latin, ductus epididymis) in this
region.
• Distal to the epididymis, the mesonephric duct acquires a thick investment of smooth
muscle and becomes the ductus deferens
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• Seminal vesicle: Lateral outgrowths from the caudal end of each mesonephric
duct gives rise to the seminal glands (vesicles).
• It produce a secretion that makes up the majority of the fluid in ejaculate and
nourishes the sperms.
• The part of the mesonephric duct between the duct of this gland and the
urethra becomes the ejaculatory duct.
• Prostate: Multiple endodermal outgrowths arise from the prostatic part of the
urethra and grow into the surrounding mesenchyme.
• The glandular epithelium of the prostate differentiates from these endodermal
cells, and the associated mesenchyme differentiates into the dense stroma and
smooth muscle of the prostate.
• Bulbourethral Glands: pea-sized structures from paired outgrowths from the
spongy part of the urethra.
• The smooth muscle fibers and the stroma differentiate from the adjacent
mesenchyme.
• The secretions of these glands contribute to the semen
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Development of female genital system
• The paramesonephric ducts develop because of the absence of MIS.
• The paramesonephric ducts form most of the female genital tract.
• The uterine tubes develop from the unfused cranial parts of these ducts.
• The caudal fused portions of these ducts form the uterovaginal primordium
which gives rise to the uterus and vagina (superior part).
• The endometrial stroma and myometrium are derived from splanchnic
mesenchyme.
• Fusion of the paramesonephric ducts also brings together a peritoneal fold that
forms the broad ligament, and two peritoneal compartments-the rectouterine
pouch and the vesicouterine pouch.
• Parametrium,- composed of loose connective tissue and smooth muscle is form
beside the broad ligament.
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Auxiliary Genital Glands in Females
• Buds grow from the urethra into the surrounding mesenchyme and form the
bilateral mucus secreting urethral glands and paraurethral glands.
• These glands correspond to the prostate in the male.
• Outgrowths from the urogenital sinus form the greater vestibular glands in the
lower third of the labia majora.
• These tubuloalveolar glands also secrete mucus and are homologous to the
bulbourethral glands in the male
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Development of uterus and vagina
• The fibromuscular wall of the vagina develops from the surrounding mesenchyme.
• Contact of the uterovaginal primordium with the urogenital sinus, forming the sinus
tubercle induces the formation of paired endodermal outgrowths-the sinovaginal
bulbs.
•
• They extend from the urogenital sinus to the caudal end of the uterovaginal
primordium. The sinovaginal bulbs fuse to form a vaginal plate.
• Later the central cells of this plate break down, forming the lumen of the vagina. The
epithelium of the vagina is derived from the peripheral cells of the vaginal plate.
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Clinical correlation
• Mesonephric Duct Remnants in Males: The cranial end of the mesonephric duct
may persist as an appendix of the epididymis, which is usually attached to the
head of the epididymis.
• Caudal to the efferent ductules, some mesonephric tubules may persist as a
small body, the paradidymis
• Mesonephric Duct Remnants in Females The cranial end of the mesonephric duct
may persist as an appendix vesiculosa.
• A few blind tubules and a duct, the epoophoron, correspond to the efferent
ductules and duct of the epididymis in the male.
• The epoophoron may persist in the mesovarium between the ovary and uterine
tube.
• Closer to the uterus, some rudimentary tubules may persist as the paroophoron.
• Parts of the mesonephric duct, corresponding to the ductus deferens and
ejaculatory duct, may persist as Gartner's duct cysts between the layers of the
broad ligament along the lateral wall of the uterus and in the wall of the vagina .
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Clinical correlation cont..
• Paramesonephric Duct Remnants in Males: cranial end of the paramesonephric
duct may persist as a vesicular appendix of the testis, which is attached to the
superior pole of the testis.
• The prostatic utricle, a small saclike structure that opens into the prostatic
urethra, is homologous to the vagina.
• Paramesonephric Duct Remnants in Females: cranial end of the paramesonephric
duct that does not contribute to the infundibulum of the uterine tube may persist
as a vesicular appendage
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DEVELOPMENT OF EXTERNAL GENITALIA
• Distinguishing sexual characteristics begins to appear during the 9th week, but
the external genitalia are not fully differentiated until the 12th week.
• Early in the fourth week, proliferating mesenchyme produces a genital tubercle
in both sexes at the cranial end of the cloacal
membrane.
• Labioscrotal swellings and urogenital folds
soon develop on each side of the cloacal
membrane.
• The genital tubercle soon elongates to form
a primordial phallus.
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• When the urorectal septum fuses with the cloacal membrane at the end of the
sixth week, it divides the cloacal membrane into a dorsal anal membrane and a
ventral urethral membrane.
• The urogenital membrane lies in the floor of a median cleft, the urethral groove,
which is bounded by the urethral folds.
• The anal and urogenital membranes rupture a week or so later, forming the anus
and urogenital orifice, respectively.
• In the female fetus the urethra and vagina open into a common cavity, the
vestibule
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Development of Male External Genitalia
• Masculinization of the indifferent external genitalia is induced by testosterone
produced by the interstitial cells of the fetal testes.
• As the phallus enlarges and elongates to become the penis, the urethral folds
form the lateral walls of the urethral groove on the ventral surface of the penis.
• This groove is lined by a proliferation of endodermal cells, the urethral plate,
which extends from the phallic portion of the urogenital sinus.
21/03/2024 50
A, The perineum during the indifferent
stage of a 17-mm, 7-week embryo
(×100). 1, developing glans of penis
with the ectodermal cord; 2,
urethral groove continuous with the
urogenital sinus; 3, urethral folds; 4,
labioscrotal swellings; 5, anus
• The urethral folds fuse with each other along the ventral surface of the penis to
form the spongy urethra.
• The surface ectoderm fuses in the median plane of the penis, forming the penile
raphe and enclosing the spongy urethra within the penis.
• At the tip of the glans penis, an ectodermal ingrowth forms a cellular ectodermal
cord, which grows toward the root of the penis to meet the spongy urethra.
• This cord canalizes and its lumen joins the previously formed spongy urethra.
• This completes the terminal part of the urethra and moves the external urethral
orifice to the tip of the glans of the penis.
• During the 12th week, a circular ingrowth of ecto-derm occurs at the periphery of
the glans penis which break down to forms the prepuce (foreskin)-a covering fold
of skin.
21/03/2024 51
• The corpora cavernosa and corpus spongiosum of the penis develop from
mesenchyme in the phallus.
• The labioscrotal swellings grow toward each other and fuse to form the scrotum.
• The line of fusion of these folds is clearly visible as the scrotal raphe.
• Agenesis of the scrotum is an extremely rare anomaly.
21/03/2024 52
Development of Female External Genitalia
• The primordial phallus in the female fetus gradually becomes the clitoris which is
still relatively large at 18 weeks.
• The urethral folds do not fuse, except posteriorly, where they join to form the
frenulum of the labia minora.
• The unfused parts of the urogenital folds form the labia minora.
• The labioscrotal folds fuse posteriorly to form the posterior labial commissure
and anteriorly to form the anterior labial commissure and mons pubis
• Most parts of the labioscrotal folds remain unfused and form two large folds of
skin, the labia majora
21/03/2024 53
Clinical Correlation
• Determination of Fetal Sex
• Visualization of the external genitalia during ultrasonography is clinically
important for several reasons, including detection of fetuses at risk of severe X-
linked disorders.
• Careful examination of the perineum may detect ambiguous genitalia .
Documentation of testes in the scrotum provides the only 100% gender
determination, which is not possible in utero until 22 to 36 weeks.
• Fetal position prevents good visualization of the perineum in 30% of fetuses.
• When there is normal sexual differentiation, the appearance of the external and
internal genitalia is consistent with the sex chromosome complement.
21/03/2024 54
• Errors in sex determination and differentiation result in various degrees of
intermediate sex-intersexuality or hermaphroditism.
• Intersex implies a discrepancy between the morphology of the gonads
(testes/ovaries) and the appearance of the external genitalia.
• Intersexual conditions are classified according to the histologic appearance of the
gonads:
• True hermaphrodites have ovarian and testicular tissue either in the same or in
opposite gonads.
• Female pseudohermaphrodites have ovaries.
• Male pseudohermaphrodites have testes
21/03/2024 55
Inguinal canal development
• The inguinal canals form pathways for the testes to descend from the dorsal
abdominal wall through the anterior abdominal wall into the scrotum.
• Inguinal canals develop in both sexes because of the morphologically indifferent
stage of sexual development.
• Degeneration of the mesonephros, causes a ligament-the gubernaculum-to
develops on each side of the abdomen from the caudal pole of the gonad.
• The gubernaculum passes obliquely through the developing anterior abdominal
wall at the site of the future inguinal canal
21/03/2024 56
• It attaches caudally to the internal surface of the labioscrotal swellings (future
halves of the scrotum or labia majora)
• The processus vaginalis is an evagination of peritoneum, that develops ventral to
the gubernaculum and herniates through the abdominal wall along the path
formed by the gubernaculum .
• The vaginal process carries along extensions of the layers of the abdominal wall
before it, which form the walls of the inguinal canal.
• These layers also form the coverings of the spermatic cord and testis.
• The opening in the transversalis fascia produced by the processus vaginalis
becomes the deep inguinal ring, and the
opening created in the external
oblique aponeurosis forms the superficial
inguinal ring.
21/03/2024 57
Decent of testis
• Testicular descent is associated with:
• Enlargement of the testes and atrophy of the mesonephroi (mesonephric
kidneys), allowing movement of the testes caudally along the posterior
abdominal wall
• Atrophy of the paramesonephric ducts induced by the mullerian-inhibiting
substance (MIS), enabling the testes to move transabdominally to the deep
inguinal rings
• Enlargement of the processus vaginalis guiding the testis through the inguinal
canal into the scrotum
• By 26 weeks, the testes have descended retroperitoneally (external to the
peritoneum) from the posterior abdominal wall to the deep inguinal rings
• This change in position occurs as the fetal pelvis enlarges and the trunk of the
embryo elongates
21/03/2024 58
• Transabdominal movement of the testes results from growth of the cranial part
of the abdomen away from the future pelvic region and controlled by androgens
(e.g., testosterone) produced by the fetal testes.
• The gubernaculum forms a path through the anterior abdominal wall for the
processus vaginalis to follow during formation of the inguinal canal.
• The gubernaculum also anchors the testis to the scrotum and appears to guide its
descent into the scrotum.
• Passage of the testis through the inguinal canal may also be aided by the
increase in intra-abdominal pressure resulting from the growth of abdominal
viscera.
• Descent of the testes through the inguinal canals into the scrotum usually begins
during the 26th week and takes 2 or 3 days.
• The testes pass external to the peritoneum and processus vaginalis. After the
testes enter the scrotum, the inguinal canal contracts around the spermatic cord.
More than 97% of full-term newborn males have both testes in the scrotum.
• During the first 3 months after birth, most undescended testes descend into the
scrotum.
21/03/2024 59
• As the testis and ductus deferens descend, they are ensheathed by the fascial
extensions of the abdominal wall.
• The extension of the transversalis fascia becomes the internal spermatic fascia.
• The extensions of the internal oblique muscle and fascia become the cremasteric
muscle and fascia.
• The extension of the external oblique aponeurosis becomes the external
spermatic fascia.
• Within the scrotum, the testis projects into the distal end of the processus
vaginalis.
• During the perinatal period, the connecting stalk of the processus normally
obliterates, forming a serous membrane-tunica vaginalis,-which covers the front
and sides of the testis
21/03/2024 60
Descent of the Ovaries
• The ovaries descend from the posterior abdominal wall to the pelvis; however,
they do not pass from the pelvis and enter the inguinal canals.
• The gubernaculum is also attached to the uterus near the attachment of the
uterine tube.
• The cranial part of the gubernaculum becomes the ovarian ligament, and the
caudal part forms the round ligament of the uterus.
• The round ligaments pass through the inguinal canals and terminate in the labia
majora.
• The relatively small processus vaginalis in the female usually obliterates and
disappears long before birth.
• A processus vaginalis that persists after birth is called a canal of Nuck.
21/03/2024 61
• Cryptorchidism or Undescended Testes Cryptorchidism (Greek, kryptos, hidden) occurs
in up to 30% of premature males and in approximately 3% to 4% of full-term males.
• This reflects the fact that the testes begin to descend into the scrotum by the end of
the second trimester.
• Cryptorchidism may be unilateral or bilateral.
• In most cases, undescended testes descend into the scrotum by the end of the first
year.
• If both testes remain within or just outside the abdominal cavity, they fail to mature and
sterility is common.
• If uncorrected, these men have a significantly higher risk of developing germ cell
tumors, especially in cases of abdominal cryptorchidism.
• Undescended testes are often histologically normal at birth, but failure of development
and atrophy are detectable by the end of the first year.
• Cryptorchid testes may be in the abdominal cavity or anywhere along the usual path of
descent of the testis, but they are usually in the inguinal canal.
• The cause of most cases of cryptorchidism is unknown, but a deficiency of androgen
production by the fetal testes is an important factor.
21/03/2024 62
• Ectopic Testes After traversing the inguinal canal, the testis may deviate from its
usual path of descent and lodge in various abnormal locations:
• Interstitial (external to aponeurosis of external oblique muscle)
• In the proximal part of the medial thigh
• Dorsal to the penis
• On the opposite side (crossed ectopia)
• All types of ectopic testis are rare, but interstitial ectopia occurs most frequently.
• An ectopic testis occurs when a part of the gubernaculum passes to an abnormal
location and the testis follows it.
21/03/2024 63
• Congenital Inguinal Hernia
• If the communication between the tunica vaginalis and the peritoneal cavity fails
to close, a persistent processus vaginalis exists.
• A loop of intestine may herniate through it into the scrotum or labium majus.
• Embryonic remnants resembling the ductus deferens or epididymis are often
found in inguinal hernial sacs.
• Congenital inguinal hernia is much more common in males, especially when
there are undescended testes.
• Congenital inguinal hernias are also common with ectopic testes and in females
with AIS.
21/03/2024 64
• Hydrocele
• Occasionally the abdominal end of the processus vaginalis remains open but is
too small to permit herniation of intestine.
• Peritoneal fluid passes into the patent processus vaginalis and forms a scrotal
hydrocele.
• If the middle part of the processus vaginalis remains open, fluid may accumulate
and give rise to a hydrocele of the spermatic cord.
21/03/2024 65

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UROGENITAL SYSTEM LECTURE SLIDES for medical students

  • 2. INTRODUCTION • Urogenital system comprise the urinary and genital system functionally. • However anatomically and embryologically they are interwoven. • The urogenital system develops from the intermediate mesenchyme derived from the dorsal body wall of the embryo. • During folding of the embryo in the horizontal plane, this mesoderm is carried ventrally and loses its connection with the somites. 21/03/2024 2
  • 3. • A longitudinal elevation of mesoderm-the urogenital ridge-forms on each side of the dorsal aorta. • The part of the urogenital ridge giving rise to the urinary system is the nephrogenic cord the part giving rise to the genital system is the gonadal ridge. • The following genes are important for the formation of the urogenital ridge: Wilms' tumor suppressor 1 (WT1), steroidogenic factor 1, and DAX1 gene, mutations of which result in X-linked adrenal hypoplasia congenita. 21/03/2024 3
  • 4. Development of urinary system The urinary system begins to develop before the genital system and consists of: • The kidneys: excrete urine • The ureters: convey urine from the kidneys to the urinary bladder • The urinary bladder: stores urine temporarily • The urethra: carries urine from the bladder to the exterior of the body 21/03/2024 4
  • 5. Development of the kidney • Three sets of kidneys develop in human embryos. • The first set-the pronephroi-is rudimentary, and the structures are never functional. • It occur in the cervical region early in the fourth week. • It soon degenerate but the length of it duct persist • The second set-the mesonephroi-is well developed and functions briefly. • It appears late in the fourth week caudal to pronephroi • It consist of glomerular and tubule • The third set-the metanephroi-becomes the permanent kidneys. • It begins to develop early in the 5th weeks and start functioning approximately 4 weeks later. • Urine formation continues throughout foetal life, excreted into the amniotic cavity and mixed with amniotic fluid. 21/03/2024 5
  • 6. Development of Permanent Kidney • Permanent kidney develop from two sources: 1. The metanephric diverticulum (ureteric bud) 2. The metanephrogenic blastema or metanephric mass of mesenchyme • The metanephric diverticulum is an outgrowth from the mesonephric duct near its entrance into the cloaca. • the metanephrogenic blastema is derived from the caudal part of the nephrogenic cord. 21/03/2024 6
  • 7. 1. The metanephric diverticulum elongates to penetrate the metanephrogenic blastema-a mass of mesenchyme. 2. The stalk of the metanephric diverticulum becomes the ureter. 3. The cranial portion of the diverticulum undergoes repetitive branching, forming the branches which differentiate into the collecting tubules of the metanephros. 21/03/2024 7
  • 8. Figure: Development of the permanent kidney. A, Lateral view of a 5-week embryo showing the primordium of the metanephros. B to E, Successive stages in the development of the metanephric diverticulum (fifth to eighth weeks). * Note: the development of the ureter, renal pelvis, calices, and collecting tubules. 21/03/2024 8
  • 9. • The first four generations of tubules enlarge and become confluent to form the major calices. • The second four generations coalesce to form the minor calices. • The end of each arched collecting tubule induces clusters of mesenchymal cells in the metanephrogenic blastema to form small metanephric vesicles. • These vesicles elongate and become metanephric tubules. 21/03/2024 9
  • 10. • The proximal ends of these tubules are invaginated by glomeruli. • The tubules differentiate into proximal and distal convoluted tubules, and the nephron loop (Henle loop), together with the glomerulus and its capsule, constitute a nephron. • Each distal convoluted tubule contacts an arched collecting tubule, and the tubules become confluent. 21/03/2024 10
  • 11. • The number of glomeruli increases gradually b/w the 10th and 18th weeks of gestation, until the 32nd week. • The fetal kidneys are subdivided into lobes. • The lobulation usually disappears during infancy as the nephrons increase and grow. • Each kidney contains 400,000 to 2,000,000 nephrons on complete growth. • The increase in kidney size after birth results mainly from the elongation of the proximal convoluted tubules as well as an increase of interstitial tissue. • Nephron formation is complete at birth except in premature infants. • Glomerular filtration begins at approximately the ninth foetal week. • Functional maturation of the kidneys and increasing rates of filtration occur after birth. 21/03/2024 11
  • 12. Uriniferous Tubules • Consist of two embryological different parts: 1. A nephron, from metanephrogenic blastema. 2. A collecting tubule derived from metanephric diverticulum (ureteric bud) • Branching of the metanephric diverticulum is dependent on induction by the metanephric mesenchyme. • Differentiation of the nephrons depends on induction by the collecting tubules. • The metanephric diverticulum and the metanephrogenic blastema interact and induce each other, a process known as reciprocal induction, to form the permanent kidneys. • Transformation of the metanephric mesenchyme to the epithelial cells of the nephron-mesenchymal-epithelial transition-is regulated by mesenchyme factors including Wnt4. 21/03/2024 12
  • 13. Figure: A to D, Diagrammatic ventral views of the abdominopelvic region of embryos and fetuses (sixth to ninth weeks) showing medial rotation and relocation of the kidneys from the pelvis to the abdomen. A and B, Observe also the size regression of the mesonephroi. C and D, Note that as the kidneys relocate, they are supplied by arteries at successively higher levels and that the hilum of the kidney is eventually directed anteromedially. 21/03/2024 13
  • 14. Changes in Position of the Kidney • Initially the metanephric kidneys (primordial permanent kidneys) lie close to each other in the pelvis, ventral to the sacrum. • As the abdomen and pelvis grow, the kidneys gradually come to lie in the abdomen and move farther apart. • They attain their adult position by the ninth week. • The ascent results mainly from the growth of the embryo's body caudal to the kidneys. • Initially the hilum of the kidney faces ventrally; however, as the kidney relocates (ascends), it rotates medially almost 90 degrees. • By the ninth week, the hilum is directed anteromedially. • Eventually the kidneys become retroperitoneal (external to the peritoneum) on the posterior abdominal wall. 21/03/2024 14
  • 15. Clinical correlation • Unilateral renal agenesis occurs approximately once in every 1000 newborn infants. • Males are affected more often than females, and the left kidney is usually the one that is absent. • It causes no symptoms because the other kidney undergoes compensatory hypertrophy and performs the function of the missing kidney. • Unilateral renal agenesis should be suspected in infants with a single umbilical artery. 21/03/2024 15
  • 16. Bilateral renal agenesis is associated with oligohydramnios (small amount of amniotic fluid) because little or no urine is excreted into the amniotic cavity. • It occurs approximately once in 3000 births, and is incompatible with postnatal life because of the associated pulmonary hypoplasia. • These infants have a characteristic facial appearance: the eyes are widely separated and have epicanthic folds, the ears are low-set, the nose is broad and flat, the chin is receding, and there are limb defects. • Most infants with bilateral renal agenesis die shortly after birth or during the first months of life. • Renal agenesis results when the metanephric diverticula fail to develop or the primordia of the ureters degenerate. • Renal agenesis probably has a multifactorial etiology. 21/03/2024 16
  • 17. • Malrotated kidney: If a kidney fails to rotate, the hilum faces anteriorly, that is, the fetal kidney retains its embryonic position. • If the hilum faces posteriorly, rotation of the kidney proceeded too far. • If it faces laterally, lateral instead of medial rotation occurred. • Abnormal rotation of the kidneys is often associated with ectopic kidneys. • Ectopic kidney: Abnormal position, ectopic kidneys are located in the pelvis, but some lie in the inferior part of the abdomen. • Pelvic kidneys and other forms of ectopia result from failure of the kidneys to alter position during embryo growth. 21/03/2024 17
  • 18. • Pelvic kidneys are close to each other and may fuse to form a discoid ("pancake"). • Ectopic kidneys receive their blood supply from blood vessels near them (internal or external iliac arteries and/or aorta). • Sometimes a kidney crosses to the other side, resulting in crossed renal ectopia with or without fusion. • An unusual type of abnormal kidney is unilateral fused kidney. In such cases, the developing kidneys fuse while they are in the pelvis, and one kidney attains its normal position, carrying the other kidney with it. • Horseshoe kidney: In 0.2% of the population, the poles of the kidneys are fused; usually the inferior poles fuse and lies in the hypogastrium, anterior to the inferior lumbar vertebrae. • Normal ascent of these fused kidneys is prevented because they are caught by the root of the inferior mesenteric artery. • It usually produces no symptoms because its collecting system develops normally and the ureters enter the bladder. • Approximately 7% of persons with Turner's syndrome have horseshoe kidneys. 21/03/2024 18
  • 19. Development of the Urethra • The epithelium of most of the male urethra and the entire female urethra is derived from endoderm of the urogenital sinus • In males, the distal part of the urethra in the glans of the penis is derived from a solid cord of ectodermal cells that grows inward from the tip of the glans and joins the rest of the spongy urethra. • The epithelium of the terminal part of the urethra is derived from the surface ectoderm. • The connective tissue and smooth muscle of the urethra in both sexes are derived from splanchnic mesenchyme. 21/03/2024 19
  • 20. Development of Urinary Bladder • the urorectal septum divides the cloaca into a dorsal rectum and a ventral urogenital sinus. • For ease the urogenital sinus is divided into three parts : A cranial, vesical part that forms most of the bladder and is continuous with the allantois • A middle, pelvic part that becomes the urethra in the bladder neck, the prostatic part of the urethra in males, and the entire urethra in females • A caudal, phallic part that grows toward the genital tubercle (primordium of the penis or clitoris) 21/03/2024 20
  • 21. • The bladder develops mainly from the vesical part of the urogenital sinus, but its trigone region is derived from the caudal ends of the mesonephric ducts. • The entire epithelium of the bladder is derived from the endoderm of the vesical part. The other layers of its wall develop from adjacent splanchnic mesenchyme. 21/03/2024 21
  • 22. Development of suprarenal gland • The cortex and medulla of the suprarenal (adrenal) glands have different origins. • The cortex develops from mesenchyme • The medulla differentiates from neural crest cells. Figure: Schematic drawings illustrating development of the suprarenal glands. A, At 6 weeks, showing the mesodermal primordium of the fetal cortex. B, At 7 weeks, showing the addition of neural crest cells. C, At 8 weeks, showing the fetal cortex and the early permanent cortex beginning to encapsulate the medulla. D and E, Later stages of encapsulation of the medulla by the cortex. F, Newborn infant showing the fetal cortex and two zones of the permanent cortex. G, At 1 year, the fetal cortex has almost disappeared. H, At 4 years, showing the adult pattern of cortical zones. Note that the fetal cortex has disappeared and that the gland is much smaller than it was at birth (F). 21/03/2024 22
  • 23. • The zona fasciculata is derived from transitional zone b/w permanent and fetal cortex. • The zona glomerulosa and zona fasciculata are present at birth. • The zona reticularis is not recognizable until the end of the third year. • The suprarenal glands of the human fetus are 10 to 20 times larger than in the adult. • Largeness of the suprarenal glands result from the extensive size of the fetal cortex, which produces steroid precursors that are used by the placenta for the synthesis of estrogen. • The suprarenal medulla remains relatively small until after birth. • The suprarenal glands rapidly become smaller as the fetal cortex regresses during the first year of infancy. • The glands lose approximately one third of their weight during the first 2 or 3 weeks after birth and do not regain their original weight until the end of the second year. 21/03/2024 23
  • 24. • During the sixth week, the cortex begins as an aggregation of mesenchymal cells on each side of the embryo between the root of the dorsal mesentery and the developing gonad • The cells that form the medulla are derived from an adjacent sympathetic ganglion, which is derived from neural crest cells. • Initially the neural crest cells form a mass on the medial side of the embryonic cortex. • As they are surrounded by the cortex, these cells differentiate into the secretory cells of the suprarenal medulla. • Later, more mesenchymal cells arise from the mesothelium and enclose the cortex. These cells give rise to the permanent cortex. 21/03/2024 24
  • 25. Clinical correlation of suprarenal gland • Congenital Adrenal Hyperplasia and Adrenogenital Syndrome • An abnormal increase in the cells of the suprarenal cortex results in excessive androgen production during the fetal period. • In females, this usually causes masculinization of the external genitalia. • Affected male infants have normal external genitalia, and the syndrome may go undetected in early infancy. • Later in childhood in both sexes, androgen excess leads to rapid growth and accelerated skeletal maturation. • The adrenogenital syndrome associated with congenital adrenal hyperplasia (CAH) manifests itself in various forms that can be correlated with enzymatic deficiencies of cortisol biosynthesis. • CAH is a group of autosomal recessive disorders that result in virilization of female fetuses. 21/03/2024 25
  • 26. • CAH is caused by a genetically determined mutation in the cytochrome P450c21- steroid 21-hydroxylase gene, which causes a deficiency of suprarenal cortical enzymes that are necessary for the biosynthesis of various steroid hormones. • The reduced hormone output results in an increased release of adrenocorticotropin from the anterior pituitary, which causes CAH and overproduction of androgens. 21/03/2024 26
  • 27. DEVELOPMENT OF THE GENITAL SYSTEM • The early genital systems in the two sexes are similar; therefore, the initial period of genital development is referred to as the indifferent stage of sexual development. • Morphological features of both sex start to manifest in the seventh week. • Development of the Gonads • The gonads: testes and ovaries are derived from three sources: • Mesothelium (mesodermal epithelium) lining the posterior abdominal wall • Underlying mesenchyme (embryonic connective tissue) • Primordial germ cells 21/03/2024 27
  • 28. Indifferent stage • The initial stages of gonadal development occur during the fifth week when a thickened area of mesothelium develops on the medial side of the mesonephros. • Proliferation of this epithelium and the underlying mesenchyme produces a bulge on the medial side of the mesonephros-the gonadal ridge. • Finger like epithelial cords-the gonadal cords-soon grow into the underlying mesenchyme. 21/03/2024 28
  • 29. • The indifferent gonad now consists of an external cortex and an internal medulla. • In embryos with an XX sex chromosome complex, the cortex of the indifferent gonad differentiates into an ovary, and the medulla regresses. • In embryos with an XY sex chromosome complex, the medulla differentiates into a testis, and the cortex regresses, except for vestigial remnants. 21/03/2024 29
  • 30. Primordial germ cells 21/03/2024 30 They are large and spherical Are visible early in the fourth week in the endodermal cells of the umbilical vesicle (yolk sac near the origin of the allantois). The primordial germ cells migrate along the dorsal mesentery of the hindgut to the gonadal ridges. During the sixth week, the primordial germ cells enter the underlying mesenchyme and are incorporated in the gonadal cords. The migration of the primordial germ cells is regulated by the genes stella, fragilis, and BMP-4.
  • 31. Sex determination • Depends on whether an X-bearing sperm or a Y-bearing sperm fertilizes the X- bearing oocyte. • Before the seventh week, the gonads of the two sexes are identical in appearance and are called indifferent gonads . • Development of the male phenotype requires a Y chromosome. • The SRY gene for a testis-determining factor (TDF) has been localized in the sex- determining, short arm region of the Y chromosome. • It is the TDF regulated by the Y chromosome that determines testicular differentiation. • The gonadal cords differentiate into seminiferous cords (primordia of seminiferous tubules). • Expression of the Sox9 and Fgf9 genes is involved in the formation of the seminiferous cords. • The absence of a Y chromosome results in the formation of an ovary. 21/03/2024 31
  • 32. • Two X chromosomes are required for the development of the female phenotype. • A number of genes and regions of the X chromosome have special roles in sex determination. • The type of gonads present then determines the type of sexual differentiation that occurs in the genital ducts and external genitalia. • Testosterone, produced by the fetal testes, dihydrotestosterone, a metabolite of testosterone, and the antimullerian hormone (AMH), determines normal male sexual differentiation. • Primary female sexual differentiation in the fetus does not depend on hormones. 21/03/2024 32
  • 33. Development of testes • The SRY gene for TDF on the short arm of the Y chromosome controls the development of the indifferent gonad into a testis. • Expression of the transcription factor SOX9 is also essential for testicular determination. • TDF induces the gonadal cords to condense and extend into the medulla of the indifferent gonad, where they branch and anastomose to form the rete testis. • The connection of the gonadal cords-seminiferous cords-with the surface epithelium is lost when a thick fibrous capsule, the tunica albuginea, develops. • The development of the dense tunica albuginea is the characteristic feature of testicular development. • Gradually the enlarging testis separates from the degenerating mesonephros and becomes suspended by its own mesentery, the mesorchium. • The seminiferous cords develop into the seminiferous tubules, tubuli recti, and rete testis. 21/03/2024 33
  • 34. 21/03/2024 34 Schematic illustrations showing differentiation of the indifferent gonads of a 5-week embryo (top) into ovaries or testes. The left side of the drawing shows the development of testes resulting from the effects of the testis-determining factor (TDF) located on the Y chromosome. Note that the gonadal cords become seminiferous cords, the primordia of the seminiferous tubules. The parts of the gonadal cords that enter the medulla of the testis form the rete testis. In the section of the testis at the bottom left, observe that there are two kinds of cells, spermatogonia, derived from the primordial germ cells, and sustentacular or Sertoli cells, derived from mesenchyme. The right side shows the development of ovaries in the absence of TDF. Cortical cords have extended from the surface epithelium of the gonad and primordial germ cells have entered them. They are the primordia of the oogonia. Follicular cells are derived from the surface epithelium of the ovary.
  • 35. • The seminiferous tubules are separated by mesenchyme that gives rise to the interstitial cells (Leydig cells). • By the eighth week, these cells begin to secrete androgenic hormones- testosterone and androstenedione, which induce masculine differentiation of the mesonephric ducts and the external genitalia. • Testosterone production is stimulated by human chorionic gonadotropin, which reaches peak amounts during the 8- to 12-week period. • In addition to testosterone, the fetal testes produce a glycoprotein, AMH, or mullerian-inhibiting substance (MIS). • AMH is produced by the sustentacular cells (Sertoli cells), which continues to puberty, after which the levels of AMH decrease. • AMH suppresses development of the paramesonephric ducts, which form the uterus and uterine tubes. • 21/03/2024 35
  • 36. • The seminiferous tubules remain solid (i.e., no lumina) until puberty, at which time lumina begin to develop. • The walls of the seminiferous tubules are composed of two kinds of cells Sertoli cells, supporting cells derived from the surface epithelium of the testis • Spermatogonia, primordial sperm cells derived from the primordial germ cells • Sertoli cells constitute most of the seminiferous epithelium in the fetal testis. • During later fetal development, the surface epithelium of the testis flattens to form the mesothelium on the external surface of the adult testis. • The rete testis becomes continuous with 15 to 20 mesonephric tubules that become efferent ductules (Latin, ductuli efferentes). • These ductules are connected with the mesonephric duct, which becomes the duct of the epididymis 21/03/2024 36
  • 37. Development of ovaries • Gonadal development occur slowly in female fetus • X-chromosome and autosomal chromosome play a role in this ovarian organogenesis • The ovary is not identifiable histologically until approximately 10th week • The gonadal cord do not become prominent but extend into the medulla and form rudimentary rete ovarii which usually degenerate and disappear with the gonadal cord. • The cortical cord extends from the surface epithelium of the developing ovary into underlying mesenchyme • As the cortical cord increase in size, primordia germ cells are incorporated in them • At approximately 16 weeks, these cords begin to break up into isolated cell clusters- primordial follicles- consists of an oogonium, derived from a primordial germ cell, surrounded by a single layer of flattened follicular cells derived from the surface epithelium. • Active mitosis of oogonia occurs during fetal life producing primordial follicles 21/03/2024 37
  • 38. Development of ovaries cont… • No oogonia is form postnatally. • Many oogonia degenerate b/4 birth, about 2 million enlarge and form the primary oocyte b/4 birth. • After birth, epithelium of the ovary flatten into a single layer of cell which continuous with the mesothelium of the peritonium at the hilum of the ovary. • The surface epithelium becomes separated from the follicles in the cortex by a thin fibrous capsule, the tunica albuginea. • As the ovary separates from the regressing mesonephros, it is suspended by a mesentery-the mesovarium. 21/03/2024 38
  • 39. • The mesonephric ducts (Wolffian ducts) play an important part in the development of the male reproductive system • Paramesonephric ducts (mullerian ducts) have a leading role in the development of the female reproductive system. • The paramesonephric ducts develop lateral to the gonads and mesonephric ducts on each side from longitudinal invaginations of the mesothelium on the lateral aspects of the mesonephroi. • The edges of these paramesonephric grooves approach each other and fuse to form the paramesonephric ducts. • The funnel-shaped cranial ends of these ducts open into the peritoneal cavity. • Caudally, the paramesonephric ducts run parallel to the mesonephric ducts until they reach the future pelvic region of the embryo. • Here they cross ventral to the mesonephric ducts, approach each other in the median plane, and fuse to form a Y-shaped uterovaginal primordium . • This tubular structure projects into the dorsal wall of the urogenital sinus and produce an elevation: sinus tubercle. 21/03/2024 39
  • 40. Development of male genital ducts and glands • The fetal testes produce masculinizing hormones (e.g., testosterone) and MIS. • The Sertoli cells begin to produce MIS at 6 to 7 weeks. • The interstitial cells begin producing testosterone in the eighth week. • Testosterone, production is stimulated by human chorionic gonadotropin, stimulates the mesonephric ducts to form male genital ducts, whereas MIS causes the paramesonephric ducts to disappear by epithelial-mesenchymal transformation. • Under the influence of testosterone produced by the fetal testes in the eighth week, the proximal part of each mesonephric duct becomes highly convoluted to form the epididymis. • As the mesonephros degenerates, some mesonephric tubules persist and are transformed into efferent ductules. • These ductules open into the duct of the epididymis (Latin, ductus epididymis) in this region. • Distal to the epididymis, the mesonephric duct acquires a thick investment of smooth muscle and becomes the ductus deferens 21/03/2024 40
  • 41. • Seminal vesicle: Lateral outgrowths from the caudal end of each mesonephric duct gives rise to the seminal glands (vesicles). • It produce a secretion that makes up the majority of the fluid in ejaculate and nourishes the sperms. • The part of the mesonephric duct between the duct of this gland and the urethra becomes the ejaculatory duct. • Prostate: Multiple endodermal outgrowths arise from the prostatic part of the urethra and grow into the surrounding mesenchyme. • The glandular epithelium of the prostate differentiates from these endodermal cells, and the associated mesenchyme differentiates into the dense stroma and smooth muscle of the prostate. • Bulbourethral Glands: pea-sized structures from paired outgrowths from the spongy part of the urethra. • The smooth muscle fibers and the stroma differentiate from the adjacent mesenchyme. • The secretions of these glands contribute to the semen 21/03/2024 41
  • 43. Development of female genital system • The paramesonephric ducts develop because of the absence of MIS. • The paramesonephric ducts form most of the female genital tract. • The uterine tubes develop from the unfused cranial parts of these ducts. • The caudal fused portions of these ducts form the uterovaginal primordium which gives rise to the uterus and vagina (superior part). • The endometrial stroma and myometrium are derived from splanchnic mesenchyme. • Fusion of the paramesonephric ducts also brings together a peritoneal fold that forms the broad ligament, and two peritoneal compartments-the rectouterine pouch and the vesicouterine pouch. • Parametrium,- composed of loose connective tissue and smooth muscle is form beside the broad ligament. 21/03/2024 43
  • 44. Auxiliary Genital Glands in Females • Buds grow from the urethra into the surrounding mesenchyme and form the bilateral mucus secreting urethral glands and paraurethral glands. • These glands correspond to the prostate in the male. • Outgrowths from the urogenital sinus form the greater vestibular glands in the lower third of the labia majora. • These tubuloalveolar glands also secrete mucus and are homologous to the bulbourethral glands in the male 21/03/2024 44
  • 45. Development of uterus and vagina • The fibromuscular wall of the vagina develops from the surrounding mesenchyme. • Contact of the uterovaginal primordium with the urogenital sinus, forming the sinus tubercle induces the formation of paired endodermal outgrowths-the sinovaginal bulbs. • • They extend from the urogenital sinus to the caudal end of the uterovaginal primordium. The sinovaginal bulbs fuse to form a vaginal plate. • Later the central cells of this plate break down, forming the lumen of the vagina. The epithelium of the vagina is derived from the peripheral cells of the vaginal plate. 21/03/2024 45
  • 46. Clinical correlation • Mesonephric Duct Remnants in Males: The cranial end of the mesonephric duct may persist as an appendix of the epididymis, which is usually attached to the head of the epididymis. • Caudal to the efferent ductules, some mesonephric tubules may persist as a small body, the paradidymis • Mesonephric Duct Remnants in Females The cranial end of the mesonephric duct may persist as an appendix vesiculosa. • A few blind tubules and a duct, the epoophoron, correspond to the efferent ductules and duct of the epididymis in the male. • The epoophoron may persist in the mesovarium between the ovary and uterine tube. • Closer to the uterus, some rudimentary tubules may persist as the paroophoron. • Parts of the mesonephric duct, corresponding to the ductus deferens and ejaculatory duct, may persist as Gartner's duct cysts between the layers of the broad ligament along the lateral wall of the uterus and in the wall of the vagina . 21/03/2024 46
  • 47. Clinical correlation cont.. • Paramesonephric Duct Remnants in Males: cranial end of the paramesonephric duct may persist as a vesicular appendix of the testis, which is attached to the superior pole of the testis. • The prostatic utricle, a small saclike structure that opens into the prostatic urethra, is homologous to the vagina. • Paramesonephric Duct Remnants in Females: cranial end of the paramesonephric duct that does not contribute to the infundibulum of the uterine tube may persist as a vesicular appendage 21/03/2024 47
  • 48. DEVELOPMENT OF EXTERNAL GENITALIA • Distinguishing sexual characteristics begins to appear during the 9th week, but the external genitalia are not fully differentiated until the 12th week. • Early in the fourth week, proliferating mesenchyme produces a genital tubercle in both sexes at the cranial end of the cloacal membrane. • Labioscrotal swellings and urogenital folds soon develop on each side of the cloacal membrane. • The genital tubercle soon elongates to form a primordial phallus. 21/03/2024 48
  • 49. • When the urorectal septum fuses with the cloacal membrane at the end of the sixth week, it divides the cloacal membrane into a dorsal anal membrane and a ventral urethral membrane. • The urogenital membrane lies in the floor of a median cleft, the urethral groove, which is bounded by the urethral folds. • The anal and urogenital membranes rupture a week or so later, forming the anus and urogenital orifice, respectively. • In the female fetus the urethra and vagina open into a common cavity, the vestibule 21/03/2024 49
  • 50. Development of Male External Genitalia • Masculinization of the indifferent external genitalia is induced by testosterone produced by the interstitial cells of the fetal testes. • As the phallus enlarges and elongates to become the penis, the urethral folds form the lateral walls of the urethral groove on the ventral surface of the penis. • This groove is lined by a proliferation of endodermal cells, the urethral plate, which extends from the phallic portion of the urogenital sinus. 21/03/2024 50 A, The perineum during the indifferent stage of a 17-mm, 7-week embryo (×100). 1, developing glans of penis with the ectodermal cord; 2, urethral groove continuous with the urogenital sinus; 3, urethral folds; 4, labioscrotal swellings; 5, anus
  • 51. • The urethral folds fuse with each other along the ventral surface of the penis to form the spongy urethra. • The surface ectoderm fuses in the median plane of the penis, forming the penile raphe and enclosing the spongy urethra within the penis. • At the tip of the glans penis, an ectodermal ingrowth forms a cellular ectodermal cord, which grows toward the root of the penis to meet the spongy urethra. • This cord canalizes and its lumen joins the previously formed spongy urethra. • This completes the terminal part of the urethra and moves the external urethral orifice to the tip of the glans of the penis. • During the 12th week, a circular ingrowth of ecto-derm occurs at the periphery of the glans penis which break down to forms the prepuce (foreskin)-a covering fold of skin. 21/03/2024 51
  • 52. • The corpora cavernosa and corpus spongiosum of the penis develop from mesenchyme in the phallus. • The labioscrotal swellings grow toward each other and fuse to form the scrotum. • The line of fusion of these folds is clearly visible as the scrotal raphe. • Agenesis of the scrotum is an extremely rare anomaly. 21/03/2024 52
  • 53. Development of Female External Genitalia • The primordial phallus in the female fetus gradually becomes the clitoris which is still relatively large at 18 weeks. • The urethral folds do not fuse, except posteriorly, where they join to form the frenulum of the labia minora. • The unfused parts of the urogenital folds form the labia minora. • The labioscrotal folds fuse posteriorly to form the posterior labial commissure and anteriorly to form the anterior labial commissure and mons pubis • Most parts of the labioscrotal folds remain unfused and form two large folds of skin, the labia majora 21/03/2024 53
  • 54. Clinical Correlation • Determination of Fetal Sex • Visualization of the external genitalia during ultrasonography is clinically important for several reasons, including detection of fetuses at risk of severe X- linked disorders. • Careful examination of the perineum may detect ambiguous genitalia . Documentation of testes in the scrotum provides the only 100% gender determination, which is not possible in utero until 22 to 36 weeks. • Fetal position prevents good visualization of the perineum in 30% of fetuses. • When there is normal sexual differentiation, the appearance of the external and internal genitalia is consistent with the sex chromosome complement. 21/03/2024 54
  • 55. • Errors in sex determination and differentiation result in various degrees of intermediate sex-intersexuality or hermaphroditism. • Intersex implies a discrepancy between the morphology of the gonads (testes/ovaries) and the appearance of the external genitalia. • Intersexual conditions are classified according to the histologic appearance of the gonads: • True hermaphrodites have ovarian and testicular tissue either in the same or in opposite gonads. • Female pseudohermaphrodites have ovaries. • Male pseudohermaphrodites have testes 21/03/2024 55
  • 56. Inguinal canal development • The inguinal canals form pathways for the testes to descend from the dorsal abdominal wall through the anterior abdominal wall into the scrotum. • Inguinal canals develop in both sexes because of the morphologically indifferent stage of sexual development. • Degeneration of the mesonephros, causes a ligament-the gubernaculum-to develops on each side of the abdomen from the caudal pole of the gonad. • The gubernaculum passes obliquely through the developing anterior abdominal wall at the site of the future inguinal canal 21/03/2024 56
  • 57. • It attaches caudally to the internal surface of the labioscrotal swellings (future halves of the scrotum or labia majora) • The processus vaginalis is an evagination of peritoneum, that develops ventral to the gubernaculum and herniates through the abdominal wall along the path formed by the gubernaculum . • The vaginal process carries along extensions of the layers of the abdominal wall before it, which form the walls of the inguinal canal. • These layers also form the coverings of the spermatic cord and testis. • The opening in the transversalis fascia produced by the processus vaginalis becomes the deep inguinal ring, and the opening created in the external oblique aponeurosis forms the superficial inguinal ring. 21/03/2024 57
  • 58. Decent of testis • Testicular descent is associated with: • Enlargement of the testes and atrophy of the mesonephroi (mesonephric kidneys), allowing movement of the testes caudally along the posterior abdominal wall • Atrophy of the paramesonephric ducts induced by the mullerian-inhibiting substance (MIS), enabling the testes to move transabdominally to the deep inguinal rings • Enlargement of the processus vaginalis guiding the testis through the inguinal canal into the scrotum • By 26 weeks, the testes have descended retroperitoneally (external to the peritoneum) from the posterior abdominal wall to the deep inguinal rings • This change in position occurs as the fetal pelvis enlarges and the trunk of the embryo elongates 21/03/2024 58
  • 59. • Transabdominal movement of the testes results from growth of the cranial part of the abdomen away from the future pelvic region and controlled by androgens (e.g., testosterone) produced by the fetal testes. • The gubernaculum forms a path through the anterior abdominal wall for the processus vaginalis to follow during formation of the inguinal canal. • The gubernaculum also anchors the testis to the scrotum and appears to guide its descent into the scrotum. • Passage of the testis through the inguinal canal may also be aided by the increase in intra-abdominal pressure resulting from the growth of abdominal viscera. • Descent of the testes through the inguinal canals into the scrotum usually begins during the 26th week and takes 2 or 3 days. • The testes pass external to the peritoneum and processus vaginalis. After the testes enter the scrotum, the inguinal canal contracts around the spermatic cord. More than 97% of full-term newborn males have both testes in the scrotum. • During the first 3 months after birth, most undescended testes descend into the scrotum. 21/03/2024 59
  • 60. • As the testis and ductus deferens descend, they are ensheathed by the fascial extensions of the abdominal wall. • The extension of the transversalis fascia becomes the internal spermatic fascia. • The extensions of the internal oblique muscle and fascia become the cremasteric muscle and fascia. • The extension of the external oblique aponeurosis becomes the external spermatic fascia. • Within the scrotum, the testis projects into the distal end of the processus vaginalis. • During the perinatal period, the connecting stalk of the processus normally obliterates, forming a serous membrane-tunica vaginalis,-which covers the front and sides of the testis 21/03/2024 60
  • 61. Descent of the Ovaries • The ovaries descend from the posterior abdominal wall to the pelvis; however, they do not pass from the pelvis and enter the inguinal canals. • The gubernaculum is also attached to the uterus near the attachment of the uterine tube. • The cranial part of the gubernaculum becomes the ovarian ligament, and the caudal part forms the round ligament of the uterus. • The round ligaments pass through the inguinal canals and terminate in the labia majora. • The relatively small processus vaginalis in the female usually obliterates and disappears long before birth. • A processus vaginalis that persists after birth is called a canal of Nuck. 21/03/2024 61
  • 62. • Cryptorchidism or Undescended Testes Cryptorchidism (Greek, kryptos, hidden) occurs in up to 30% of premature males and in approximately 3% to 4% of full-term males. • This reflects the fact that the testes begin to descend into the scrotum by the end of the second trimester. • Cryptorchidism may be unilateral or bilateral. • In most cases, undescended testes descend into the scrotum by the end of the first year. • If both testes remain within or just outside the abdominal cavity, they fail to mature and sterility is common. • If uncorrected, these men have a significantly higher risk of developing germ cell tumors, especially in cases of abdominal cryptorchidism. • Undescended testes are often histologically normal at birth, but failure of development and atrophy are detectable by the end of the first year. • Cryptorchid testes may be in the abdominal cavity or anywhere along the usual path of descent of the testis, but they are usually in the inguinal canal. • The cause of most cases of cryptorchidism is unknown, but a deficiency of androgen production by the fetal testes is an important factor. 21/03/2024 62
  • 63. • Ectopic Testes After traversing the inguinal canal, the testis may deviate from its usual path of descent and lodge in various abnormal locations: • Interstitial (external to aponeurosis of external oblique muscle) • In the proximal part of the medial thigh • Dorsal to the penis • On the opposite side (crossed ectopia) • All types of ectopic testis are rare, but interstitial ectopia occurs most frequently. • An ectopic testis occurs when a part of the gubernaculum passes to an abnormal location and the testis follows it. 21/03/2024 63
  • 64. • Congenital Inguinal Hernia • If the communication between the tunica vaginalis and the peritoneal cavity fails to close, a persistent processus vaginalis exists. • A loop of intestine may herniate through it into the scrotum or labium majus. • Embryonic remnants resembling the ductus deferens or epididymis are often found in inguinal hernial sacs. • Congenital inguinal hernia is much more common in males, especially when there are undescended testes. • Congenital inguinal hernias are also common with ectopic testes and in females with AIS. 21/03/2024 64
  • 65. • Hydrocele • Occasionally the abdominal end of the processus vaginalis remains open but is too small to permit herniation of intestine. • Peritoneal fluid passes into the patent processus vaginalis and forms a scrotal hydrocele. • If the middle part of the processus vaginalis remains open, fluid may accumulate and give rise to a hydrocele of the spermatic cord. 21/03/2024 65