Development of the Urinary System• Urinary and genital systems are closely

associated• Both develop from intermediate mesoderm

– 7th- 28th somite level(3-d week)– Nephrogenic mass (cord)

• Dorsal side of coelom each cord produces a bulge into the coelom called the urogenital ridge

• Urinogenital Ridge– Form the urinary and genital structures– Nephrogenic tissue from 7-14th somite breaks

up into segments called nephrotomes

Fig. 1 - Transverse section and dorsal view of an embryo (trilaminar)

(ca. 21 days) Fig. 1 - Transverse section and dorsal view of an embryo (trilaminar)

(ca. 21 days) Fig. 1 - Transverse section and dorsal view of an embryo (trilaminar)

(ca. 21 days) Transverse section of the three-layered embryo towards the end of the 3rd week of development.

1.Paraxial mesoderm2.Intermediate mesoderm3.Lateral mesoderm4.Notochord5.Amnion6.Intraembryonic coelom7.Endoderm8.Ectoderm9.Somatopleural (mesoderm and ectoderm)10Splanchnopleural (mesoderm and endoderm)11.Neural groove12.Neural ridge

1.Neural tube2.Notochord3.Aorta dorsalis4.Dorsal mesentery5.Intestinal tube6.Ectoderm7.Somite8.Inferior cardinal vein9.Mesonephric duct (Wolffian duct)10.Mesonephric tubule11.Urogenital ridge

Mesonephros enlargement point A

The urinary tract develops from the 3rd week of the embryonic period from the intermediate mesoderm as well as from the urogenital sinus. The kidneys develop from the 4th week in three steps: As a first one, a cranial anlage, the pronephros, forms that then later atrophies in the 8th week and is never active functionally. It is followed by a further anlage from the intermediate mesoderm, the mesonephros, that is formed between the 6th and 10th weeks, but is only transitory, and the anlage of the definitive kidneys, the metanephros. They develop from a metanephric anlage (mesodermal origin) and the ureter anlage (that has its origin in the caudal part of the wolffian duct).The urine-excreting part of the kidneys, the nephron, mainly arises from the metanephric anlage (glomerulus, proximal, intermediate and distal tubules), while the rest of the upper urinary tract (collecting ducts, calices, renal pelvis and ureter) develop from the ureter anlage.

The lower urinary tract differentiates from the cloaca between the 5th and 8th weeks in that it becomes subdivided by the urorectal septum. The ventral part of the cloaca forms the primary urogenital sinus, out of which the urethra forms in the lower part and the bladder in the upper part. The ureter anlage discharges into the upper posterior wall of the urogenital sinus. In males, the wolffian duct remains present and forms a connection to the genital tract in the lower part of the urogenital sinus.The numerous induction mechanisms between ureter anlage and metanephric mesenchyma during the development of the renal system, as well as the ascent of the kidneys, originating at the level of the sacrum and moving up to the diaphragm at the end of the development, make it possible for a large number of abnormalities to arise. Many remain asymptomatic whereas others are not compatible with survival.

Intermediate Mesoderm• Cervical region

– Loses contact with the somite• Forms nephrotomes which acquire a lumen and

open medially into the intra-embryonic coelom• Caudal growth unite and form longitudinal duct• Branches off dorsal aorta form glomeruli (ext & int)

• Thoracic, lumbar, sacral regions– Loses contract with coelomic cavity

• Ext glomeruli fail to develop• Segmentation disappears (nephrogenic cord)

– 2 or more excretory tubules per prior segment

Urinary Tubules

• Associated with a vascular tuft = glomerulus– Open tubules = external glomerulus

• One end opens into the coelom• Other end opens into the collecting duct

– Closed tubules = internal glomerulus• Open only into the collecting ducts

Formation of 3 kidney systems • Pronephros (simplest & most primitive)

– 7-10 solid or tubular arranged cell groups in the cervical region (head kidney)

– Gone by the end of the 4th week

• Mesonephros (intermediate-more advanced)– Appear during regression of pronephros– 10-26th somite level

• Metanephros (permanent kidney)– Begins to develop early in 5th week, functions by

the 11th week

1.Nephrogenic cord2.Mesonephric duct (Wolff)1+2.Mesonephros3.Intestinal tube4.Cloaca5.Atrophying nephrotomes 6.Yolk sac (umbilical vesicle)7.Allantois8.Outflow of the mesonephric duct into the cloaca

Pronephros (forekidney): transitory structure

Mesonephros• Tubules develop from nephrogenic cord (NC)

– Opens into the excretory/mesonephric duct– Gone by week 10 in females, in males some

tubules persist & become vas deferens

• Approximately 38 pairs of closed tubules– S shaped bend– Surrounds internal glomerulus

• Mesonephric duct develops laterally from NC & extends from 8th somite to urinogenital sinus

Mesonephros: transitory kidney

1.Nephrogenic cord2.Mesonephric duct1+2.Mesonephros3.Intestine4.Cloaca5.Atrophied nephrotome6.Yolk sac (umbilical vesicle)7.Allantois8.Outflow of the mesonephric ductinto the cloaca9.Ureter bud (anlage)

1.Neural tube2.Notochord3.Aorta dorsalis4.Dorsal mesentery5.Intestinal tube6.Ectoderm7.Somite8.Inferior cardinal vein9.Mesonephric duct (Wolffian duct)10.Mesonephric tubule11.Urogenital ridge

Mesonephros enlargement point A

1a-Pronephros (atrophying)1b-Mesonephros (atrophying)2-Mesonephric duct(Wolffian duct)3-Nephrogenic cord4-Ureter anlage5-Metanephric blastema6-Liver anlage7-Cloaca

The metanephros: definitive kidney 5th week

Metanephric outflow

1.Cloaca2.Ureter anlage3.Metanephric blastema2+3.Metanephros4.Mesonephric duct (Wolffian duct)5.Nephrogenic cord4+5.Mesonephros

Metanephros• Nephrons/tubules develop from nephrogenic

mass (26th-28th somite level)– Located lateral to mesonephric duct– Internal dense layer which forms tubules/nephrons– Outer loose layer forms connective tissue capsule

• Duct system derived from ureteric bud– Ureter, renal pelvis, calyces, collecting ducts– Ureteric bud elongates and makes contact with

nephrogenic mass which surrounds bud like a cap

• Tubules are closed (internal glomerulus)• Migrate from pelvis to abdomen as fetus grows

– Blood supply from aorta changes as ascent occurs

• Becomes functional in second ½ of pregnancy

1.Ureter2.Renal pelvis3.Vena renalis4.Arteria renalis5.Major calix6.Minor calix7.Cortex8.Capsula renis9.Medullary rays10.Papilla renalis11.Sinus renalis12.Columna renalis13.Medullary pyramid

Kidney at the end of its development

1.Ureter2.Major calix3.Minor calix4.Renal pelvis

5.Collecting duct6.Metanephric vesicle 7.Kidney lobe

Schematic cut through the kidney (sagittal section)

8.Distal tubule9.Proximal tubule10.Glomerulus11.Connecting tubule13.Intermediate tubule

Enlargement of the inset Nephron

Cloaca

• Caudal end of the hindgut (dilated)

• In 3 week old embryo the hindgut ends blindly at the cloacal membrane

• Blind end = cloaca

• Allantois and mesonephric ducts open into cloaca

• Cloaca is latin for sewer, a system of pipes used to transport human waste

Urinary Bladder• During 4th to 7th week cloaca subdivided

– Posterior portion = anorectal canal– Anterior portion = primitive urogenital sinus

• Bladder is formed from primitive urogenital sinus– Bladder is upper and largest part of urogenital sinus

• Initially bladder is continuous with the allantois– Allantois lumen obilterated & urachus formed

connecting apex of bladder with umbilicus– In adult urachus = median umbilical ligament

• Ureter is outgrowth of mesonephric duct– Terminal ends of mesonephric ducts become part of

bladder wall– Ureter obtains separate entrance into bladder with time

Production of urine by fetus

• Fetal urine mixes with amniotic fluid• Amniotic fluid enters fetal intestinal tract

where it is absorbed into bloodstream• From the bloodstream to the placenta

which transfers metabolic waste to the mother

• Fetal kidneys are not necessary for exchange of waste products

During the fifth and sixth weeks of development, the mature kidneys lie in the pelvis with their hila pointed anteriorly. As the pelvis and abdomen grow, the kidneys slowly move upward. By the seventh week, the hilum points medially and the kidneys are located in the abdomen. As the embryo continues to grow in a caudal direction, the kidneys are left behind and eventually come to lie in a retroperitoneal position at the level of L1 by the ninth week of development. In the meantime, the kidneys have completed rotation and the hila now face anteromedially.

Ascent of Kidneys

Development of the reproductive system

• Makes its appearance during 5th & 6th week– Indifferent stage-sex cannot be determined

• Gonads (testes & ovaries) develop from– Coelomic epithelium– Inner mesenchyme tissue– Primordial germ cells

• Thickening of ventromedial surface of urogenital ridge forming genital ridge

Genital ridge

• Covered by coelomic epithelium– Primary sex cords

• Grow into underlying mesenchyme

• Inner mass is composed of mesenchyme

• Outer layer called cortex

• Inner layer called medulla– Males- medulla differentiates, cortex regresses– Females-cortex develops, medulla regresses

Primordial Germ Cells (PGC)

• Differentiate in the neck of the yolk sac– Early in the 4th week

• Migrate to genital ridge– Amoeboid movement– By end of 6th week the PGC become

incorporated into the primary sex cords– migration of primordial germ cells

Development of Genital Ducts• Indifferent stage

– Both male and female genital ducts present• Male develop from mesonephric/wolffian ducts• Female develop from paramesonephric/mullerian

duct– Undifferentiated gonad

• Males:Mesonephric ducts form epididymis, ductus deferens, ejaculatory duct– Cranial mesonephric tubules efferent ducts

• Open into epididymis

– Process begins about the 3rd month

Development of Genital Ducts

• Females: Paramesonephric duct/Mullerian duct develops on each side of the body– Longitudinal invagination of coelomic

epithelium on the lateral surface of mesonephros

– Ducts open into coelom– Runs along side of mesonephric duct– Fuse at caudal end

• Y shaped uterovaginal complex uterus & vagina– uterovaginal complex

Development of testes• Primary sex cords of testes containing the

primordial germ cells = testes cords– Well defined cords within the medulla– Contain two types of cells

• Epithelial cells Sertoli cells• Primordial germ cells spermatoblasts

– development of testes

• Testes cords remain solid until puberty– Canalize to form seminiferous tubules (ST),

tubuli recti, rete testis• ST seperated from each other by mesenchyme that

gives rise to interstitial cells (Cells of Leydig)

Development of the Ovaries

• Primary sex cords are not well defined– Extend into the medulla but later dissappear

• PGC migrate near the cortex (surface epithelium– Forms cortical cords– At about 16th week cortical cords break up into

isolated clusters called primordial follicles– development of ovary