RENAL - Embryology of the Urological Tract

Question 1

When does the urogenital tract commence development?

Answer 1

Week 4

Question 2

RECAP: What happens during first week of development?

Answer 2

OVULATION
FERTILISATION
MITOSIS AND IMPLANTATION

Question 3

RECAP: What happens during second week of development?

Answer 3

Bilaminar disc formation
- Cell differentiation

Question 4

RECAP: What happens during third week of development?

Answer 4

Trilaminar disc formation
- Gastrulation

Question 5

RECAP: What happens during fourth week of development?

Answer 5

• Neurulation (folding of endoderm)
• Differentiation of mesoderm (into paraxial, intermediate and lateral plate mesoderm)
• Lateral and cephalocaudalfolding begins to occur

Question 6

Describe the embryological origins of:
- Upper urinary system
- Genital system
- Lower urinary system

Answer 6

• Intermediate mesoderm
• Intermediate mesoderm
• Endoderm (primitive hindgut)

Question 7

What are the three stages of kidney development?

HINT- They develop cranio-caudally

Answer 7

• PRONEPHROS - rudimentary - develops in cervical region
• MESONEPHROS - forms in thoracolumbar region and functions for short time in early fetal period
• METANEPHROS - true permanent kidney - develops more caudally down in pelvis and ascends during development

Question 8

Describe the pronephros.

Answer 8

• Intermediate mesoderm condenses to form a long bilateral structure called the nephrogenic cord. Runs from the cervical region, all the way down towards the cloaca (future bladder, urethra and hindgut)
• In the cervical region, the pronephros begins to develop.
• Collection of cell 7-10 cell groups and is formed of segmented ducts and nephrotomes
• Begins its development at the start of week 4, and by the end of week 4, it has begun to degenerate

Question 9

Describe the mesonephros. PART 1

Answer 9

• As the pronephros begins its regression, the mesonephros begins its formation (aka week 4)
• Nephrogenic cord within the thoracolumbar region begins to differentiate
• At the beginning of week 5, the mesonephros has developed into two distinct structures: the mesonephric duct and mesonephric tubules
• The mesonephros functions until around week 10 and is known as the primitive urinary system
• Distally, the mesonephric duct drains into the cloaca (future bladder and urethra)

Question 10

Describe the mesonephros. PART 2

Answer 10

• Mesonephric tubules grow towards the developing aorta
• Aorta undergoes angiogenesis to form primitive glomeruli that connect with the mesonephric tubules
• Tubules become S shaped and form a capsule around the primitive glomeruli (primitive Bowman’s capsule)
• Mesonephros is also forming a gonadal ridge (future genitalia)

Question 11

Describe the root of the primitive waste system developed during the mesonephros

Answer 11

Aorta > Glomerulus > Mesonephric tubule > Mesonephric duct > Cloaca > Allantois

Question 12

Describe the metanephros. PART 1

Answer 12

• Begins formation during the 5th week in the pelvic region
• intermediate mesoderm condenses to form the metanephric blastema
• Blastema forms growth factors that stimulate development of the ureteric bud
• Ureteric bud forms growth factors that in turn stimulate the metanephric blastema aka receptive induction

Question 13

Describe the metanephros. PART 2

Answer 13

• Once the ureteric bud meets the metanephric blastema, it dilates and begins dividing
• The collecting system is formed first
• Ureteric bud > renal pelvis > major calyces > minor calyces > collecting tubules

Question 14

Describe the metanephros. PART 3

Answer 14

• Collecting tubules each have their own metanephric tissue caps
• Caps condense into renal vesicles (induced by growth factors)
• Form S shaped metanephric tubules, which develop towards invaginating capillaries
• Metanephric vesical > metanephric tubule > DCT > PCT > Bowman’s capsule
• The loop of Henle is formed slightly later, once the Bowman’s capsule has connected with the glomerulus. It lengthens from the PCT and DCT

Question 15

Describe the metanephros. PART 4

Answer 15

• Initially, blood supply to the developing metanephros originates from the common iliac arteries
• As the kidneys ascend, they pick up the renal arteries
• Urine production begins at week 12 – amniotic fluid swallowed by the fetus recycles through the kidneys
• Nephrons continue to form up to birth, with around 1 million in each kidney
• At birth, the kidneys have a lobular appearance, which disappears as nephrons grow after birth

Question 16

Describe bladder development. PART 1

Answer 16

• Bladder and urethra develop from endoderm
• Ureteric bud drains into mesonephric duct
• Cloaca rsorbs mesonephric duct up to point of joining of duct and bud
• Now separated, ureters move more laterally and duct moves downwards

Question 16

Describe bladder development. PART 2

Answer 16

• Cloaca forms urorectal septum, separates into urogenital sinus anteriorly and anal canal posteriorly
• Bladder is continuous with allantois
• At around 20 weeks (after urethra formation), allantois regresses and leaves urachus

Question 17

Describe urethra development.

Answer 17

The urogenital sinus can be separated into three parts:
- The uppermost and largest part will become the bladder
- The middle part is a narrow canal that will become the pre-prostatic, prostatic and membranous parts of the urethra
- The final part is known as the phallic part and will become the penile urethra

Question 18

What is development of the genital system based on?

Answer 18

• Presence or absence of Y chromosome
• Presence of Y - Sex determining region of Y chromosome (SRY gene) encodes for testis-determining factor
• Absence of Y - No testis-determining factor produced leads to female development

Question 19

Describe the indifferent stage in gonad development (for both sexes).

Answer 19

• Invagination of primordial germ cells into genital ridges - occurs in week 6
• Germ cells are endodermal in origin - originate from yolk sac and become gametes
• Upon invagination, epithelium of ridge penetrates underlying mesenchyme forming primitive sex cords

Question 20

Describe testes development. PART 1

Answer 20

• Develop centrally within medulla
• Primitive sex cords continue to proliferate and, under the influence of the SRY gene, form the medullary cords of the testis (aka the seminiferous tubules)
• Extending out towards the hilum, the cords break up into thinner strands, connecting the seminiferous tubules to the mesonephric duct and forming the rete testis
• A layer of dense fibrous connective tissue develops between the cords and surface epithelium, which we know as the tunica albuginea

Question 21

Describe testes development. PART 2

Answer 21

Three cell types become apparent in the developing testes:
- Primitive germ cells (endodermal origin - future sperm)
- Sertoli cells (mesodermal origin – facilitate spermatogenesis)
- Interstitial cells of Leydig (mesodermal origin – produce testosterone by week 8)
- 1 and 2 are cords, 3 sits between cords

Question 22

Describe the indifferent stage in genital duct development.

Answer 22

• Initially, both male and female embryos have two pairs of genital ducts: The mesonephric (Wolffian) ducts and the paramesonephric (Mullerian) ducts
• Once the Sertoli cells have developed in the developing male testes, they produce anti-mullerian hormone, which causes the paramesonephric ducts to degenerate

Question 23

What is the effect of the Leydig cells?

Answer 23

• Secretes testosterone - stimulate mesonephric ducts to become efferent ductules, vas deferens, seminal vesicles and epididymis

Question 24

Describe the indifferent stage in external genitalia development.

Answer 24

- The external genitalia is formed from the cloacal membrane, and begins in week 3 with mesenchyme cells migrating around the membrane to form the cloacal folds - Cranially, the cloacal folds join to form the genital tubercle - By week 6, the folds have differentiated into urethral and anal folds - External to the urethral folds, genital swellings appear

Question 25

Describe the next stage of male external genitalia development. PART 1

Answer 25

- Testosterone is converted to dihydrotestosterone (DHT) by the enzyme 5-alpha reductase. It is DHT that stimulates differentiation of external genitalia in the male! - Rapid elongation of the genital tubercle occurs, and the tubercle is now known as the phallus - As the phallus elongates, the urethral folds are pulled towards each other, forming the urethral groove. The epithelium of the groove is called the urethral plate

Question 26

Describe the next stage of male external genitalia development. PART 2

Answer 26

- By the end of month 3, the urethral folds close over the urethral plate, forming the penile urethra. Distally, the groove stays open. - In month 4, the external urethral meatus is formed by invaginating ectoderm cells - The scrotal swellings move caudally over time

Question 27

The testes develop in the abdominal cavity. How would they descend into the scrotum?

Answer 27

- Gubernaculum is a fibrous cord that connects to the testes, and pulls them down through the inguinal canal - Gubernaculum gets longer the further down the testes descend - As the testes are pulled down, they pull a bit of peritoneum with them: the processus vaginalis - By week 12, the testes have reached the inguinal region. By week 33, they have reached the scrotum

Question 28

Describe the coverings of the testes.

Answer 28

Testis covered by a fold of processus vaginalis (tunica vaginalis) Testes also covered in the layers of abdominal wall which it passes - External abdominal oblique – external spermatic fascia - Transversalis fascia – internal spermatic fascia - Internal abdominal oblique – cremasteric fascia and muscle