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Genital System

J.-H. Lue

Sexual differentiation is sequential process:


.genetic (chromosomal) sex -- determined at fertilization
.gonad sex -- is differentiated after 7th week
.phenotypic sex -- under normal circumstances, chromosomal
sex agrees with the phenotypic sex.

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GONADS
(i) mesothelium (mesodermal epithelium)

(ii) mesenchyme (intermediate mesoderm)); (i)+(ii) ® genital


or gonad ridges (5th week),

(iii) primordial germ cells (PGC))—endodermal cells of the yolk


sac near the origin of allantois, migrate along the dorsal mesentery
to the gonadal ridge at 6th week 2
3w

primordial germ cells (PGC)—endodermal cells of the yolk


sac near the origin of allantois, migrate along the dorsal mesentery
to the gonadal ridge at 6th week

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6w

primordial germ cells (PGC)—endodermal cells of the yolk


sac near the origin of allantois, migrate along the dorsal mesentery
to the gonadal ridge at 6th week

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INDIFFERENT GONADS

.gonadal ridge (medial side of the mesonephros)¬ proliferation of


mesothelium and underlying mesenchyme

.consists of : (i). Outer cortex + (ii). Inner medulla

.in embryo with XY, medulla® testis, with XX sex chromosome,


cortex® ovary 5
.determines by the testis-determining factor (TDF) (SRY gene)
.in embryos with XY sex chromosome, PGC + medulla® primary sex cords®
testicular (seminiferous) or medullary cords
.development of the tunica albuginea is a characteristic and diagnostic feature of
testicular development
.testicular cords® seminiferous tubules, tubule recti, &rete testis
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.testicular cords® seminiferous
tubules, tubule recti,&rete testis

• mesenchyme surrounding the


seminiferous® interstitial cells (of
Leydig), 8th week begin to secret
testosterone

• walls of seminiferous tubules, lumina


begin to develop at puberty:
puberty (i).
supporting or sustentacular cells of
Sertoli (¬ germinal epithelium);
epithelium
(ii)..spermatogonia (¬PGC
PGC))

.rete testis « persistent excretory


mesonephric tubules (15-20) ® efferent
ductules (ductuli efferentes)

.mesonephric or Wolffian duct®


epididymis, vas deferens, seminal vesicles
and ejaculatory ducts
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.in embryos with XX sex chromosome,
primary sex cords® degenerate

.in 10th week, cortical cords formed; in


16th week, cortical cords® primordial
follicles:(i).oogonium (¬PGC), (ii).
Flattened follicular cells (¬mesothelium)

.germinal epithelium-- peritoneum


.no oogonia form postnatally in full term humans
.oogonium® primary oocyte® primary follicle
.mesenchyme surrounding the follicles® ovarian
stroma
.as the ovary separates from the regressing
mesonephros, it becomes suspended by its own
mesentery, mesovarium
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TDF No TDF
medullary cord cortical cord

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Indifferent stage (6th week)

7w 9w

(a) Paramesonephric duct (Mullerian duct)


funnel-like cranial portion« coelomic cavity
fused caudal portion® uterine canal® paramesonephric tubercle

(b) Mesonephric duct (Wolffian duct) 10


8w

*MIS -- 140,000 daltons Testosterone


a large dimeric glycoprotein external genitalia simulated
formed by Sertoli cells of growth of penis, scrotum
fetal and new born testis and prostate
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.develops from the
mesonephric ducts
.mesonephric tubules®
efferent ductules
.mesonephric ducts®
epididymis, ejaculatory ducts
.mesonephric duct +
surrounding mesenchyme (®
muscular coat)® ductus
deferens
. outbudding of tail of
mesonephric duct® seminal
vesicle 6-week

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4th month

.develops from the mesonephric ducts


.mesonephric tubules® efferent ductules
.mesonephric ducts® epididymis, ejaculatory ducts
.mesonephric duct + surrounding mesenchyme (® muscular
coat)® ductus deferens
.outbudding of tail of mesonephric duct® seminal vesicle
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Newborn

outbudding of tail of mesonephric duct® seminal vesicle


Primitive urogenital sinus (PUS) ® urethra® prostate
gland and bulbourethral gland 15
11-week

11-week

16-week

Prostate gland -- arise from the prostatic (endodermal) portion of the urethra
and grow into the surrounding mesenchyme
.endodermal cells® glandular .mesenchyme®dense stroma
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epithelium and smooth muscle
Newborn

bulbourethral gland -- arise from the spongy (endodermal) portion of the urethra

.endodermal cells® glandular .mesenchyme®dense stroma and


epithelium smooth muscle 17
develops from the
paramesonephric ducts
(a). cranial vertical portion® uterine
tubes® coelomic cavity
(b). horizontal portion -- crosses the
mesonephric duct
2nd month (c). caudal vertical portion®
uterovaginal primordium® (i). corpus,
(ii). cervix of uterus, (iii). part of vagina
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8-week

.formation of the broad ligaments: (i). due to the fusion of the


paramesonephric ducts.(ii). 2 mesenchymal peritoneal folds extend
between the lateral ends of the fused ducts and the walls of the pelvis

.side products: rectouterine pouch of Douglas & vesicouterine pouch


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Formation of the vagina

3rd month Newborn

9 weeks

.dual origins
(a). fused paramesonephric duct® uterovaginal primordium®
uterine canal and upper part of the vagina
(b). uterovaginal primordium contact with the primitive urogenital
sinus evaginates to form sinovaginal bulbs® vagina plate®
canalized to form lower part of the vagina 21
Formation of the vagina

9 weeks
9 weeks 3rd month
3rd month Newborn Newborn

.dual origins
(a). fused paramesonephric duct® uterovaginal primordium®
uterine canal and upper part of the vagina
(b). uterovaginal primordium contact with the primitive urogenital
sinus evaginates to form sinovaginal bulbs® vagina plate®
canalized to form lower part of the vagina 22
Auxiliary genital glands in the female

12-week

.urethral glands, paraurethral glands

Newborn

.greater vestibular glands (of Bartholin


-- outgrowth from the urogenital sinus
-- homologous to the bulbourethral glands

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Normal

Double uterus and


vagina Double uterus with
single vagina

Bicornuate uterus
Bicornuate uterus with a
rudimentary left horn

Septate uterus Unicornuate uterus


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mesenchyme cells around the urethral folds®
genital swellings (GS) (labioscrotal swelling)

in male, GS® scrotal swellings

in female, GS® labia majora

Indifferent stage

in the 4th week, mesenchyme cells from the primitive streak migrate around the cloacal
membrane® cloacal folds, cranial portion of the folds® genital tubercle (GT)

in the 6 week, cloacal membrane® urogenital membrane & anal membrane;


cloacal folds® urogenital (urethral) folds & anal folds
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under influence of androgens (¬ fetal
testes), GT® phallus

urethral folds® urethral groove, urethral


plate® penile urethra; glandular portion of
penile urethra® invaginate from the
ectodermal cells

fusion of scrotal swellings® scrotal


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septum
Newborn
10-week

under influence of androgens (¬ fetal testes), GT® phallus

urethral folds® urethral groove, urethral plate® penile urethra;


glandular portion of penile urethra® invaginate from the ectodermal
cells
fusion of scrotal swellings® scrotal septum
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Anomalies

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under influence of estrogens, GT® clitoris

urethra folds® labia minora; GS® labia


majora

urogenital groove® vestibule

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Newborn
5 months

under influence of estrogens, GT® clitoris

urethra folds® labia minora; GS® labia majora


urogenital groove® vestibule
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Sex abnormalities as reflected in the
duct system and external genitalia

hermaphroditism (intersexuality)
true hermaphrodite
pseudohermaphrodites

male pseudohermaphrodites
female pseudohermaphrodites

Congenital virilizing adrenal hyperplasia

Fusion of the labia majora


Enlargement of the clitoris

female pseudohermaphrodites 32
Descent of testis

.2nd -- 7th month development


.development of inguinal canal & formation of the
vaginal process
.the site of the inguinal canal in the fetus is first
indicated by the gubernaculum (mesonephros
degenerate, from inferior poles of gonad to the internal
surface of the labioscrotal swelling

.the processus vaginalis develops on each side ventral


to the gubernaculum
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.the processus vaginalis develops on each side ventral to the gubernaculum
.the opening produced in the transversalis fascia by the processus vaginalis
becomes the deep inguinal ring
.the opening in the external oblique aponeurosis becomes the superficial
inguinal ring
.testis -- posterior abdominal wall -- deep inguinal rings -- inguinal canal --
superficial inguinal rings --scrotum 34
Possible factors that affect the descent of testis

(a). the pelvis enlarges

(b). the trunk of the embryo elongates

(c). an increase in intrabdominal pressure (the


growth of the abdominal viscera)

(d). the hormone control, e.g. gonadotropins &


androgens
clinical evidence: by the administration of the
gonadotropic hormones to treat the cryptorchidism
(e). the exact role of gubernaculum is unknown

(f). descent through the inguinal canal begins during


week 28 and takes 2 to 3 days

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Descent of ovary

ovaries -- posterior abdominal wall -- inferior to


the pelvic brim
• do not normally enter the inguinal canals, the
processus vaginalis normally obliterates
completely
• the gubernaculum attaches to the uterus®
ovarian ligament & round ligament of
uterus

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PGC

TDF

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GENITAL SYSTEM

Dr. J.-H. Lue Embryology

Sexual differentiation is sequential process:


.genetic (chromosomal) sex -- determined at fertilization;
.gonad sex -- is differentiated after 7th week;
.phenotypic sex -- under normal circumstances, chromosomal sex agrees with
the phenotypic sex.
GONADS
.derived from 3 sources
(i) mesothelium (mesodermal epithelium)
(ii) mesenchyme (intermediate mesoderm); (i)+(ii)  genital or gonad
ridges (5th week),
(iii) primordial germ cells (PGC)—endodermal cells of the yolk sac near
the origin of allantois, migrate along the dorsal mesentery to the gonadal
ridge at 6th week
INDIFFERENT GONADS
.gonadal ridge (medial side of the mesonephros) proliferation of mesothelium
and underlying mesenchyme
.consists of : (i). Outer cortex + (ii). Inner medulla
.in embryo with XX sex chromosome, cortex ovary
; with XY, medulla testis
TESTIS
.determines by the testis-determining factor (TDF) (SRY gene)
.in embryos with XY sex chromosome, PGC + medulla primary sex cords
testicular (seminiferous) or medullary cords
.testicular cords 1)seminiferous tubules; 2)tubule recti, &3)rete testis
.mesenchyme surrounding the seminiferous interstitial cells (of Leidig), 8th
week begin to secret testosterone
.walls of seminiferous tubules, lumina begin to develop at puberty: (i).
supporting or sustentacular cells of Sertoli ( germinal epithelium)
(mesothelium); (ii).spermatogonia (PGC)
.rete testis  persistent excretory (15-20) mesonephric tubules efferent
ductules (ductuli efferentes)
.mesonephric ( Wolffian) duct 1)epididymis, 2)vas deferens, 3)seminal
vesicles and 4)ejaculatory ducts

1
OVARY
.in embryos with XX sex chromosome, primary sex cords degenerate
.in 10th week, cortical cords formed; in 16th week, cortical cords primordial
follicles:(i).oogonium(PGC), (ii). flattened follicular cells (mesothelium)
.germinal epithelium-- peritoneum
.no oogonia form postnatally in full term humans
.oogonium primary oocyte primary follicle
.mesenchyme surrounding the follicles ovarian stroma
.as the ovary separates from the regressing mesonephros, it becomes suspended
by its own mesentery, mesovarium
GENITAL DUCTS
Indifferent stage (6th week)
(a). paramesonephric ducts (Mullerian duct):
(i). funnel-like cranial portion  coelomic cavity
(ii). fused caudal portion uterine canal paramesonephric or Mullerian
tubercle
(b). mesonephric ducts (Wolffian duct)
Differentiation of the duct system
Influence of sex gland on further sex differentiation:
Testis

Mullerian testosterone
inhibiting substance (MIS)* (Leydig‘s cells) (8th week)

paramesonephric ducts mesonephric ducts stimulated


suppressed (7th week) (efferent ductus ejaculatory duct)

*MIS -- 140,000 daltons testosterone


a large dimeric glycoprotein external genitalia simulated
formed by Sertoli cells of growth of penis, scrotum
fetal and new born testis and prostate

2
Ovary

estrogens (including maternal and placental sources)

paramesonephric ducts stimulated external genitalia stimulated


(uterine tube, uterus, upper portion (labia, clitoris, lower of vagina)
portion of vagina)

Genital ducts in the male


.develops from the mesonephric ducts
.mesonephric tubules efferent ductules
.mesonephric ducts epididymis, vas deferens, ejaculatory ducts
.outbudding of tail of mesonephric duct seminal vesicle
.mesonephric duct + surrounding mesenchyme ( muscular coat) ductus
deferens
Auxiliary glands in the male
prostate gland -- arise from the prostatic (endodermal) portion of the urethra
and grow into the surrounding mesenchyme
.endodermal cells glandular epithelium
.mesenchymedense stroma and smooth muscle
bulbourethral gland -- outgrowths from the spongy part of the urethra
.endodermal cells glandular epithelium
.mesenchyme dense stroma and smooth muscle
Genital ducts in the female
.develops from the paramesonephric ducts:
(a). cranial vertical portion uterine tubes coelomic cavity
(b). horizontal portion -- crosses the mesonephric duct
(c). caudal vertical portion uterovaginal primordium (i). corpus, (ii).
cervix of uterus, (iii). part of vagina
.two mesonephric (Wolffian) ducts regress Gartner‘s ducts
.formation of the broad ligaments: (i). due to the fusion of the
paramesonephric ducts.(ii). 2 mesenchymal peritoneal folds extend
between the lateral ends of the fused ducts and the walls of the pelvis
.side products: rectouterine pouch of Douglas & vesicouterine pouch

3
Formation of the vagina
.dual origins:
(a). fused paramesonephric duct uterovaginal primordium 1)uterine canal
and 2)upper part of the vagina
(b). uterovaginal primordium contact with the primitive urogenital sinus
evaginates to form sinovaginal bulbs vagina plate canalized to form
lower part of the vagina
Auxiliary genital glands in the female
.urethral glands paraurethral glands
.greater vestibular glands (of Bartholin)
-- outgrowth from the urogenital sinus
-- homologous to the bulbourethral glands
Anomalies
.duplication and atresia of uterine canal
(a). uterus didelphys, (b). bicornuate uterus, (c). bicornuate uterus with a
rudimentary horn, (d). unicornuate uterus
EXTERNAL GENITALIA
Indifferent stage
.in the 4th week, mesenchyme cells from the primitive streak migrate around
the cloacal membrane cloacal folds, cranial portion of the folds genital
tubercle (GT)
.in the 7 week, cloacal membrane 1)urogenital membrane &2)anal
membrane
cloacal folds 1)urogenital (urethral) folds &2)anal folds
.mesenchyme cells around the urethral folds genital swellings (GS)
(labioscrotal swelling)
(i). in male, GS scrotal swellings
(ii). in female, GS labia majora
External genitalia in the male
.under influence of androgens ( fetal testes), GT phallus
.urethral folds urethral groove; urethral plate penile urethra
glandular portion of penile urethra invaginate from the ectodermal cells
.fusion of scrotal swellings scrotal septum
Anormalies
.hypospadias
.epispadias
.ectopia or exstrophy of the bladder

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External genitalia in the female.under influence of estrogens
.GT clitoris
.urethra folds labia minora
.GS labia majora
.urogenital groove vestibule
Sex abnormalities as reflected in the duct system and external genitalia
.true hermaphrodite
.pseudohermaphrodites (intersexuality)
.male pseudohermaphrodites
.female pseudohermaphrodites
Descent of testis (2nd -- 7th month development)
.development of inguinal canal & formation of the vaginal process
.the site of the inguinal canal in the fetus is first indicated by the
gubernaculum (mesonephros degenerate, from inferior poles of gonad to
the internal surface of the labioscrotal swelling)
.the processus vaginalis develops on each side ventral to the gubernaculum
.the opening produced in the transversalis fascia by the processus vaginalis
becomes the deep inguinal ring
.the opening in the external oblique aponeurosis becomes the superficial
inguinal ring
.testis posterior abdominal wall deep inguinal rings inguinal canal
superficial inguinal rings scrotum
possible factors that affect the descent of testis:
(a). the pelvis enlarges
(b). the trunk of the embryo elongates
(c). an increase in intrabdominal pressure (the growth of the abdominal viscera)
(d). the hormone control, e.g. gonadotropins & androgens
clinical evidence: by the administration of the gonadotropic hormones to
treat the cryptorchidism
(e). the exact role of gubernaculum is unknown
(f). descent through the inguinal canal begins during week 28 and takes 2 to 3
days
Descent of ovary
ovaries posterior abdominal wall inferior to the pelvic brim
.do not normally enter the inguinal canals, the processus vaginalis normally
obliterates completely
.the gubernaculum attaches to the uterus ovarian ligament
& round ligament of uterus

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