1. Development of urinary and genital system

2. Origins intermediate mesoderm→ urogenital ridge→
→ nephrogenic cord (laterally)
→ genital ridge (medially)
coelomic epithelium (mesothelium) of posterior body wall
germinal cells
migration from endoderm of yolk sac
cloaca → sinus urogenitalis
mesenchyme above and on either side of the cloacal membrane → genital tubercle, urethral folds and labioscrotal / genital swellings
ectoderm → fossa navicularis of male urethrae, prepuce

3. Ductus mesonephricus Wolffi Mesonephric duct
originates in intermediate mesoderm
cranially blind-ended as pronephric duct
caudally continues as duct of mesonephroi
elongates and empties into cloaca
important for development of excretory part of male genital system
lower portion constitutes ureteric bud (diverticulum metanephricum)

6. Ductus mesonephricus Wolffi Mesonephric duct
♀ ureteral bud → trigonum vesicae, ureter, pelvis renales, calices majores et minores, ductus papilalles, ductus colligentes
rudiments: epoophoron, ductus longitudinalis Gartneri
♂ similar + excretory genital ducts (ductus epididymidis, ductus deferens, glandulae vesiculosae + ductus excretorius, ductus ejaculatorius)

7. Ductus paramesonephricus Mülleri Paramesonephric duct
6th week: laterally from Wolffian duct infolding of coelomic epithelium between 3th thoracic segment and posterior wall of sinus urogenitalis
cranial end – opens into the coelomic cavity
caudal end – fusions and empty into sinus urogenitalis medially to ostium of Wolffian duct
formed by infolding
cranially communicates with coelomic cavity
upper portion is laterodorsally to Wolffian duct, lower portion crosses it ventrally
caudally paired duct fuses and empties into cloaca
important for development of excretory part of female genital system

8. Development of kidney předledvina = pronephros
nefunkční, „otevřená“
prvoledvina = mesonephros
základ pohlavní žlázy
konečná ledvina = metanephros

9. Development of kidney origin from intermediate mesoderm
longitudinal swellings of mesoderm on either side of dorsal aorta→ urogenital ridge → nephrogenic cord → origin of urinary / excretory system
genital ridge → origin of genital system

10. Paraxial mesoderm Intermediate mesoderm Lateral mesoderm Notochord Amnion Intraembryonic coelom Endoderm Ectoderm Somatopleural (mesoderm and ectoderm) Splanchnopleural (mesoderm and endoderm) Neural groove Neural ridge 10 10

12. 4 structural origins of urinary system
metanephric blastema
nephron (glomerular capsule of Bowman and tubules)
ureteric bud
collecting ducts → ureter
blood vessels – branches of dorsal aorta
cells from neural crest (regulation, secretion)

13. Pronephros pl. pronephroi
forms excretory system in cyclostomata (lamprey)
in humans at first described by Czech anatomist Jan Jánošík
stalks of cranial nephrotomes
from 21th day (4 nephrotomes) in cervical region
rudimental, soon disappear
tubuli pronephrici
ductus pronephricus remains to next stage of development 13

15. Mesonephros excretory system in chondrichthyes (sharks) and fishes
origin is nephrogenic blastema (intermediate mesoderm)
vesicle elongates to ductus mesonephricus Wolffi
in stage of nephrotomes grows to the cloaca
from approximately 23th day till the end of 3th month
corpuscula mesonephrica (glomerulus) + tubuli mesonephrici (approximately 20)
caudal portions of ducts → head of epididymis 15

17. Metanephros = Definitive kidney
blastema metanephrogenicum (metanephrogenic blastema) 3th to 5th lumbar nephrotomes
development begins by the end 5th week
relative ascent during development
ureteric bud grows into the blastema – metanephrogenic cap (galea metanephrogenica) → reciprocal induction (necessary tight contact)
ureteric bud → ureter, pelvis, major calices, minor calices, papillary ducts down to collecting tubules
metanephrogenic blastema
– nephron
relative ascent: 5th – 9th week
functional from 9th week 17

19. Development of excretory duct system of kidney
metanephric diverticulum – penetrates the metanephrogenic blastema and branches:
first 4 generations → calices majores
second 4 generations → calices minores
another generations → tubuli metanephrici colligentes

20. Nephrogenesis 8th week straight collecting ducts
→ branches – arcuate collecting tubules →
their endings induce arise of metanephrogenic caps
metanephric vesicle → comma-shaped vesicle → S-shaped vesicle → connects to branches of ureteric bud
maturation of renal corpuscle
distance between glomeruli and medulla defines the age
the oldes are juxtamedular nephrones
distal portion → metanephric vesicle
proximal portions elongate to form metanephric tubules and connect to collecting ducts
glomeruli invaginate into distal portions of metanephric tubules

27. Completion of development
definitive location in the 9th week (finished ascent)
10th-23th week:
number of glomeruli increases until final count ( – )
fetal kindeys divided into distinct lobes
disappears during childhood
after birth the expansion of interstitium and elongation of loops of Henle

31. Developmental defects
atypical shapes (lobulated, horseshoe, duplex, sigmoid, cake kidney…)
cystic, polycystic kidneys
renal agenesis
dysplastic kidney
ectopic kidney (ren dystopicus)

33. Development of urinary excretory system
origin is intermediate mesoderm
vacuolization → canal
ductus pronephricus
ductus mesonephricus Wolffi
in the stage of nephrotomes connects to the cloaca
ureteric bud grows into metanephrogenic blastema → ureter, renal pelvis, major calices, minor calices, papillary ducts down to collecting tubules 33

35. Cloaca widening of aboral end of hindgut
endoderm in area of membrana cloacalis is closely attached to superficial ectoderm of proctodeum
membrana cloacalis = endoderm of cloaca + ectoderm of proctodeum
orifice of allantois

36. Urorectal septum (Septum urorectale)
6th week: mesenchymal septum grows in craniocaudal direction toward the cloacal membrane and divides cloaca into →
dorsal primitive rectum and upper portion of canalis analis
ventral sinus urogenitalis
and divides cloacal membrane into →
membrana analis
membrana urogenitalis
differentiates into perineal body (corpus perineale)

39. Urogenital sinus (Sinus urogenitalis)
8th week: fusion of septum urorectale and membrana cloacalis →
membrana urogenitalis (urogenital membrane)
membrana analis (anal membrane)
sinus urogenitalis primordialis (primordial urogenital sinus)
canalis vesicourethralis (vesico-urethral canal)
sinus urogenitalis definitivus (definitive urogenital sinus)
pars pelvica (pelvic part)
pars phallica (phallic part) 39

41. Functional classification of sinus urogenitalis
3 parts:
upper (pars allantoica) → urachus → disappears
midle (canalis vesicourethralis) → urinary bladder
lower (pars pelvica et pars phallica) → female urethra, most of male urethra, prostate gland and bulbourethral gland

42. Development of urinary excretory system
urinary bladder
epithelium from endoderm of sinus urogenitalis (pars pelvica)
other layers derived from adjacent splanchnic mesoderm
urachus
separation of urinary and genital excretory tract
material of trigonum vesicae derived from tissue of Wolffian duct
female urethra
epithelium derived from endoderm
larger proximal portion from pars urethralis canalis vesicourethralis – lined by transitional epithelium
smaller distal portion from pars pelvica sinus urogenitalis – lined by nonkeratinized stratified squamous epithelium 42

45. Development of urinary excretory system
male urethra
epithelium derived from endoderm
posterior wall of pars intramuralis + upper half of pars prostatica (cranially to orifice of genital system) derived from tissue of Wolffian duct
lower half of pars prostatica + pars intermedia in male from pars pelvica of sinus urogenitalis
pars spongiosa u.m. + gl. bulbourethralis Cowperi from pars phallica sinus urogenitalis
distal part on the top of glans penis derived from ectodermal glandular plate (lamella glandularis) → fossa navicularis
other layers derived from adjacent splanchnic mesoderm

46. Developmental defects
uterer duplex (double ureter), ureter fissus
exstrophy of urinary bladder (exstrophia v.u.)
agenesis of urinary bladder
ectopic urinary bladder
double urinary bladder
fistula congenita vesicouterina / vesicovaginalis
urachal cyst
urachal sinus
urachal fistula
hypospadias / epispadias

47. Suprarenal / adrenal glands
2 different origins:
cortex: coelomic epithelium grows into radix mesenterii and gonadal primordium
proliferate and grow into adjacent mesenchyme int he area of intermediate mesoderm (5th-6th week)
medulla: cells derived from neural crest form adjacent sympathetic ganglion

48. Congenital adrenal hyperplasia (CAH)
autosomal recessive congenital defect synthesis of steroid hormones
deficiency of some of five necessary enzymes, most often 21-hydroxylase
hyperplasia of cells of adrenal cortex
overproduction of androgenes in fetal age
defect of enzymes for hormone synthesis
female fetuses – prenatal virilization
male – late diagnosis based on rapid growth in childhood

49. Development of gonads
genetic determination of sex during fertilization
indifferent stage → testes / ovaries
3 sources of cells:
coelomic epithelium (mesothelium) of posterior body wall
mesenchyme (intermediate mesoderm)
primordial germ cells (cellulae germinales primordiales)
epiblast → endoderm of yolk sac

50. Indifferent gonads
end of 4th week: formation of genital ridge (crista gonadalis)
mesothelial swelling with adjacent mesenchyme
3th-6th week: migration of primordial germ cells from wall of yolk sac cranially and dorsally along the mesogastrium dorsale
induction of invagination of coelomic epithelium into mesenchyme → gonadal cords / primordial sex cords (chordae sexuales primordiales gonadales)
→ indifferent gonad
outer cortex
inner medulla

52. Sex determination chromosomal sex
determined during fertilization – XX or XY
region SRY of chromosome Y (sex-determining region of chromosome Y)
expression of TDF (testes-determining factor) induces development of testes
in testes differentiate testosterone producing cells
→ promotes survival of Wolffian duct
→ primary sex cords differentiate into seminiferous tubules
AMH (anti-müllerian hormone, MIS) → promotes development of Müllerian duct
deficiency of SRY → development of ovaries

53. Development of testes from 7th week
TDF induces proliferation of primordial sex cords (chordae gonadales) and their invasion to the deep  medullary cords
form tubuli seminiferi
branch and anastomose  rete testis
connecting to the rest of mesonephric tubules (15-20)  ductuli efferentes testis
empty into ductus mesonephricus Wolffi  ductus epididymidis
connection with surface cortex
disappears (10th-12th week )
mesenterium – mesorchium
tunica albuginea

54. Development of testicular cells
tubuli seminiferi (seminiferous )
primordial germ cells → spermatogonia
Sertoli cells (nurse cells; sustenocytes)
produce AMH (anti-müllerian hormone) = MIS (müllerian inhibiting substance)
separated by mesenchyme → interstitial Leydig cells → from 8th week produce testosterone, androstendion
stimulated by hCG from cytotrophoblast

57. Development of ovaries
from 12th week
primary sex cords degenerate  rudimental rete ovarii
formation of secondary sex cords
from coelomic epithelium into adjacent mesenchyme
incorporation with primordial germ cells
16th week: formation of individual primordial follicles with oogonia
surface epithelium
simple cuboid  mesovarium
tunica albuginea

59. Prenatal development of ovum
each primordial follicle contains oogonium
oogonia surrounded by 1 layer of flattened cells derived from sex cords
oogonia can emerge after birth!
degeneration of oogonia before birth, approximately 2 millions remain
after birth oogonia differentiate into the primary oocytes

60. Development of male genital system
tubuli mesonephrici 
ductuli efferentes in caput epididymidis (connection to testis)
ductus mesonephricus Wolffi 
ductus epididymidis
ductus deferens
glandulae vesiculosae
ductus ejaculatorius
ureteric bud (origin of trigonum vesicae, ureter, pelvis, calices, collecting ducts)
ductus mesonephricus Mülleri – disappears

61. Developmental rudiments
remnant of mesonephric excretory system
paradidymis (of Giraldes)
ductuli aberrantes (sup. + inf.)
appendix epididymidis
remnant of Müllerian duct
appendix testis

62. Development of prostate gland
10th week: endoderm of prostatic part of urethra → glandular epithelium
similarly develop also glandulae bulbourethrales
evaginations into adjacent mesenchyme → surrounding connective tissue and smooth muscle (fibromuscular stroma)

63. Female developmental rudiments
epoophoron Rosenmülleri – in mesosalpinx
- ductuli transversi (remnants of mesonephric tubules)
- ductus longitudinalis Gartneri (remnant of Wolffian duct near the edge of uterus in ligamentum latum uteri)
paroophoron Kobelti (remnant of mesonephric tubules)
in mesosalpinx closer to uterus
appendices vesiculosae (= hydatis Morgagni) – remnant of Wolffian duct

64. Development of male genital system
testosterone deficiency → tubuli et ductus mesonephrici degenerate
ductus mesonephricus Mülleri
cranial and middle portion → Fallopian tubes
caudal portions fuse → primordium uterovaginale (uterovaginal primordium)
formation of lig. latum uteri

67. Development of uterus and vagina
uterus: merged ductus paramesonephrici
vagina: 3 sources
uterovaginal primordium (primordium uterovaginale) → upper portion (derived from coelomic epithelium)
sinus urogenitalis (endoderm) – roof→ unpaired tuberculum sinuale Mülleri → paired bulbi sinuvaginales → merge to form unpaired vaginal plate (lamella vaginalis) → epithelium
elongates by proliferation and luminize in 11th week
adjacent mesenchyme → fibromuscular wall of vagina
hymen formed by invagination of posterior wall of urogenital sinus → ruptures perinatally

71. Development of external genitalia
4th-7th week: indifferent stage
4th week: mesenchyme on the upper edge of cloacal membrane → phallic tubercle (tuberculum phallicum) → phallus
different appearance visible from 9th week
fully differentiated from 12th week

72. Development of external genitalia♀
clitoris
labia minora
labia majora ♂
penis
urethra – pars spongiosa
scrotum
indifferent stage
(4th-7th week)
tuberculum phallicum / genitale (phallic / genital tubercle)
plicae urethrales (urethral folds / swellings)
tubercula labioscrotalia (labioscrotal / genital swellings)

74. Development of male external genitalia
fusion of urethral folds → unpaired urethral groove → raphe penis
formation of pars spongiosa urethrae
glandular plate derived from ectoderm of phallus → connection to pre-existing proximal part
12th week – circular invagination of ectoderm around glans penis → preputium
labioscrotal / genital swellings fuse to form unpaired scrotum → raphe scroti
descent of testes

76. Hypospadias 1:300 – most common developmental defect of penis
urethral orifice on the ventral side of penis (facies urethralis)
glandular / coronary
penile
penoscrotal
perineal

77. Epispadias 1:30 000 urethral orifice on the dorsal side of penis
often associated with
defects of urinary
bladder

79. Descent of testes (Descensus testium)
relative:
enlargement of testes
widening of processus vaginalis peritonei
atrophy of tubuli mesonephrici et ductus paramesonephrici (influence of AMH)
relative descent (body elongation)
absolute:
gubernaculum testis (condensation of connective tissue)
descent through inguinal canal (26th week) takes 2-3 days
protrusion of peritoneum (processus vaginalis peritonei) and corresponding layer of abdominal wall independently on the descent of testes

80. Descent of testes (Descensus testium)

81. Descent of testes (Descensus testium)
gubernaculum testis
upper portion degenerates
lower portion remains as → lig. scrotale in scrotum

82. Cryptorchism unilateral / bilateral
undescended testis → immaturity → atrophy → sterility
possibly located in abdominal cavity or other location in the way of descent (retention)
can be deflected and descend (ectopy):
outward to aponeurosis of internal oblique abdominal muscle (intersticial ectopy)
to the perineum (perineal ectopy)
cause: defect in androgene production?
increased risk of tumor (seminom)

83. Development of female external genitalia
phallus ceases to grow → clitoris
urethral folds do not merge → formation of labia minora
merge only on dorsal site → frenulum labii minoris
labioscrotal / genital swellings merge partially:
dorsally → commissura labiorum posterior
ventrally → commissura labiorum anterior, mons pubis
formation of labia majora

85. Descent of ovaries (Descensus ovarii)
relative descent (body elongation)
from the posterior body wall to the lesser pelvis
gubernaculum ovarii
upper portion → lig. ovarii proprium
lower portion → lig. teres uteri
descent through inguinal canal into labia majora

86. Developmental defects of sex determination
intersex (intersexus)
true hermaphroditism: testicular and ovarial tissue
female pseudohermaphroditism
virilization of external genitalia
associated with androgenital syndrome
male pseudohermaphroditism
deficiency of testosterone, AMH
testicular feminization syndrome = syndrome of androgen insensitivity

87. Summary of male development 1.
indifferent gonad → testes
cortex → tubuli seminiferi, medulla → rete testis
gubernaculum testis → lig. scrotale
tubuli mesonephrici
→ ductuli efferentes testis
→ paradidymis (rudiment)

88. Summary of male development 2.
ductus mesonephricus Wolffi →
ductus epididymidis, ductus deferens, ductus ejaculatorii, glandulae vesiculosae
ureter, pelvis renalis, calices renales, ductus papillares, tubuli colligentes, tubuli reunientes
appendix epididymidis (rudiment)
ductus paramesonephricus Mülleri →
– appendix testis (rudiment)
utriculus prostaticus (rudiment)

89. Summary of male development 3.
sinus urogenitalis → vesica urinaria, urethra + its glands (except fossa navicularis), prostata, gl. bulbourethralis, colliculus seminalis
tuberculum genitale → penis (glans penis, corpora cavernosa penis, corpus spongiosum penis)
plicae urogenitales → facies urethralis penis
tubercula labioscrotalia → scrotum

90. Developmental defects
hypospadia (1:300) – urethral orifice ventrally
epispadia (1:30 000) – urethral orifice dorsally
cryptorchism = undescended testes (3-4%)
ectopy of testis
crossed testis
inversion of testis
anorchism
polyorchism
congenital inguinal hernia
hydrocoele (hydrocoelia)

91. Summary of female development 1.
indifferent gonad → ovaries
cortex → folliculi ovarii, medulla → rete ovarii → degenerates
gubernaculum → ligamentum ovarii proprium, ligamentum teres uteri
tubuli mesonephrici →
epoophoron (rudiment)
paraoophoron (rudiment)

92. Summary of female development 2.
ductus mesonephricus Wolffi →
ureter, pelvis renalis, calices renales, ductus papillares, ductus colligentes, tubuli reunientes
ductus longitudinalis Gartneri (rudiment)
? appendix vesiculosa (rudiment)
ductus paramesonephricus Mülleri →
– tuba uterina, uterus, upper part of vagina

93. Summary of female development 3.
sinus urogenitalis →
vesica urinaria, urethra and its glands, part of vagina, glandulae vestibulares majores et minores
tuberculum genitale → clitoris (glans clitoridis), corpora cavernosa clitoridis, bulbus vestibuli
plicae urogenitales → labia minora
tubercula labioscrotalia → labia majora

94. Female developmental defects 1.
anovaria
ovotestis
polycystic ovaria (ovaria polycystica)
agenesis tubae uterinae
atresia tubae uterinae
ostium accessorium tubae uterinae
tuba uterina accessoria

95. Female developmental defects 2.
agenesis uteri
uterus arcuatus
uterus duplex
uterus septatus, subseptatus
uterus unicornis, bicornis
uterus bicervicalis
uterus didelphys
agenesis vaginae
vagina duplex
clitoris bifidus
hymen imperforatus