Urogenital System Development Notes

The Urogenital System

Overview

  • Chapters:

    • Chapter 15: Development of the Urinary System

    • Chapter 16: Development of the Reproductive System

Anatomy

  • Components: Kidneys, ureters, bladder, and urethra.

  • Vasculature:

    • Renal arteries: Supply blood to the kidneys from the abdominal aorta.

    • Renal veins: Drain blood from the kidneys into the inferior vena cava.

  • Urine Flow: Kidneys produce urine (waste) that drains into the ureters, then to the urinary bladder, and finally out through the urethra.

  • Functional Unit: The nephron.

Physiology

  • Functions:\Elimination of waste by filtering blood to form urine. Regulates blood volume & pressure, electrolytes & metabolites, blood pH.\Part of Vitamin D synthesis pathway

  • Regulation: Regulated by adrenal gland-derived aldosterone & posterior pituitary-derived antidiuretic hormone. Other factors also regulate the integrative functions of the kidneys.

Development

  • Origin: Intermediate mesoderm from cervical-to-sacral levels.

  • Progression: Cranial-to-caudal developmental progression via reciprocal tissue-tissue induction.

Chapter 15: Development of the Urinary System

Intermediate Mesoderm

  • Location: Located on either side of the embryo.

  • Structure: Series of longitudinal epithelial ducts & buds from cervical-to-sacral levels.

  • Gives Rise To:

    • 3 nephric structures or systems: (1) pronephros, (2) mesonephros, and (3) metanephros.

    • Adrenal glands (mesoderm > cortex; neural crest > medulla).

    • Gonads: ovaries & testes.

    • Genital duct system.

Developmental Progression

  • Direction: Cranial-to-sacral, ventral-medial.

  • Mechanism: Series of tissue induction & regression.

(1) Pronephros

  • Location: Cervical levels, C5 to C7.

  • Structure: Epithelial buds located ventromedial and adjacent to mesonephric or Wolffian duct.

  • Function: Non-functional; resemble remnants of lower vertebrate-like structures; the “first kidneys”.

  • Disappearance: Disappears around 21-25 days.

(2) Mesonephros

  • Formation: Caudal extension of mesonephric duct induces & initiates formation of mesonephric buds.

  • Contribution: Growth of mesonephric duct at lower lumbar contributes to formation of posterior wall of urinary bladder.

  • Tubules: Mesonephric tubules develop with mesonephric buds.

  • Differentiation & Regression: Cranial-to-caudal; from 40 to 20 tubules upper lumbar (L1-L3).

  • Urogenital Ridge: Region where gonads develop medial to this region.

  • Function: First kidneys to function in embryo.

  • Nephric Units: Contain functional nephric (simple nephron) units consisting of glomeruli, Bowman’s capsules, mesonephric tubules, and mesonephric ducts.

(3) Metanephros

  • Outcome: Gives rise to definitive kidneys.

  • Cell Behavior:

    • Mesenchymal-to-epithelial transition.

    • Epithelial tube formation & elongation.

    • Specification & differentiation of specialized cell types.

  • Induction: Induction of ureteric buds in sacral region from mesonephric duct.

  • Interaction: Ureteric buds sprout from mesonephric duct & interacts with overlying sacral intermediate mesoderm, developing blood vessels, and nerves to form definitive kidneys.

  • Lobes Formation: By the end of the 16th week, 14-16 lobes have formed.

Development of the Metanephros

  • Origin: Intermediate mesoderm gives rise to metanephric mesenchyme.

  • Induction: Around the 5th week, metanephric mesenchyme is induced from intermediate mesoderm.

  • Ureteric Bud: Sprouts from mesonephric (Wolffian) duct.

  • Cell-Cell Interactions: Between ureteric tip cells & cap mesenchymal cells drive branching of ureteric buds & renal lobules until ~ week 16.

  • Ureteric Buds Outcome: Give rise to collecting duct system & ureters of the kidneys.

  • Urine Flow: Urine produced by nephron flows into collecting ducts > minor calyces > major calyces > renal pelvis > ureters.

Development of Renal Pelvis & Calyces

  • Origin: Intermediate mesoderm gives rise to metanephric mesenchyme.

  • First Bifurcation: Of ureteric bud forms renal pelvis.

  • Next Four Generations: Forms major calyces.

  • Subsequent Four Generations: Leads to the formation of minor calyces.

  • Continued Bifurcation: Ureteric buds continue to bifurcate until week 32 to produce 1-3 million collecting ducts.

Development of Renal Vesicle & Nephrons

  • Requirement: Requires reciprocal cell-cell interactions & inductive signals.

  • Interactions: Between ureteric bud tip & cap mesenchyme.

  • Ureteric Stalk Signals: Via Wnt9b & Ret, induces subset of cap mesenchymal cells to aggregate & express Wnt4 & Gdnf.

  • Wnt4 Role: Required for mesenchymal-epithelial transition to form renal vesicle.

  • Vesicle Fusion: Renal vesicle fuses with ureteric stalk to form the nephron.

Development of the Suprarenal or Adrenal Gland

Adrenal Cortex

  • Hormonal Signaling: Required for stress response via the hypothalamic-pituitary-adrenal axis to produce glucocorticoids (deploy energy reserves) and aldosterone (Na regulation).

  • Origin: Originate intermediate mesoderm region adjacent to developing kidney.

  • Origin Relation: Region also gives rise to gonadal primordia.

Adrenal Medulla

  • Innervation: Adrenal medulla innervated by sympathetic preganglionic fibers (axons).

  • Function: Preganglionic fibers stimulate release of epinephrine and norepinephrine during stress, “fight or flight”.

  • Derivation: Derived from neural crest cells to differentiate into chromaffin cells.

Chapter 16: Development of the Reproductive System

Anatomy

  • Components: Testis & Ovary

  • Function: Site of spermatogenesis & oogenesis.

  • Structure: Consists of tubular structures that transport both urine & gametes.

Physiology

  • Functions:\Produce male and female gametes & reproductive hormones.\Controls reproductive behavior & physiology.

Development

  • Origin: Intermediate mesoderm, which gives rise to gonadal ridge.

  • Primordial Germ Cells (PGCs):

    • 6th week – primordial germ cells (PGCs) migrate from yolk sac into hindgut epithelium & via dorsal mesentery, into intermediate mesoderm-derived gonadal ridge.

    • PGCs induce mesenchyme to form male & female support cells (Sertoli, follicle).

  • Sex Differentiation:

    • Support cell expression of male-specific SRY protein encoded by Y chromosome gene initiates male sexual differentiation.

    • Absence of SRY protein or Y chromosome leads to female sexual differentiation.

Formation of Gonads

  • Begins with the arrival of PGCs into the intermediate mesoderm.

(A) Genital Ridge

  • Formation: Forms ~4-5 weeks

  • Location: Posterior body wall, medial to mesonephros.

  • Differentiation: In response to yolk sac-derived PGCs.

(B, C) Paramesonephric (Mullerian) Duct

  • Development: Develops from coelomic epithelium; ~6th week.

  • Location: Extends caudally; parallel & lateral to mesonephric (Wolffian) duct.

  • Fate:

    • In females, becomes fallopian tubes, uterus, cervix, and upper vagina.

    • Degenerates in males.

Mesonephric Ducts

  • Fate: Develop into male reproductive organs (i.e., epididymis, vas deferens, seminal vesicles).

  • Sertoli Cells Role: Male supporting Sertoli cells produce anti-Mullerian to cause female paramesonephric ducts to degenerate.

(D) Formation of Support Cells

  • PGCs induce coelomic epithelium lining peritoneal cavity to proliferate & differentiate into support cells.

Sex Differentiation Factors

  • (A) Bipotential Gonads: Initially have the capacity to generate both male & female reproductive structures.

  • (B) SRY Protein Expression:

    • From Y chromosome stimulates supporting cells to express Sox9.

    • Sox9 stimulates somatic supporting cells to differentiate into Sertoli (male) cells.

    • Leads to the organization of testis cords.

    • Sertoli cells also produce anti-Mullerian Hormone, which causes degeneration of female paramesonephric duct.

  • (C) Absence of SRY:

    • Somatic support cells differentiate into follicle or granulosa cells, which then surround primordial follicles.

    • Gonad then takes on ovarian fate.

Human Male and Female Gonadal Development

  • Initial State: Male & female genital systems are initially identical.

  • Male (XY):

    • Expression of SRY protein from Y chromosome.

    • Somatic support cells differentiate into Sertoli cells.

    • Sertoli cells, PGCs, & myoepithelial precursor cells organize into testes cord.

    • Sertoli cell-derived anti-Mullerian Inhibiting Hormone causes paramesonephric duct to degenerate.

    • Leydig cells produce testosterone; stimulates development of male genital duct system, 9-10 weeks.

  • Female (XX):

    • Absence of SRY protein in XX female embryo.

    • Somatic support cells differentiate into follicle cells.

    • Follicle cells then surround developing oocytes to form primordial follicles.

    • With no Leydig cells, mesonephric ducts degenerate.

    • Paramesonephric duct is retained to form female genital duct system (i.e., oviducts & uterus).

Seminal Vesicles, Prostate, and Bulbourethral Glands

  • Leydig cells produce testosterone.

  • Testosterone stimulates differentiation of mesonephric ducts into:

    • Epididymis

    • Vas deferens

    • Seminal vesicles

  • Endodermal buds from Urethra give rise to:

    • Prostate gland

    • Bulbourethral glands

  • Function: Required for sperm transport maturation, nutrient, semen production, lubrication, and production of anti-microbial & neutralizing factors.

Role of Fgf8 Expression

  • Requirement: Fgf8 is required for the formation of mesonephric tubules & ducts.

Uterus and Vagina Formation

  1. Paramesonephric (Müllerian) Ducts

    • Fuse caudally near the posterior wall of the urogenital sinus.

    • Fusion continues cranially—this is known as "zipping" of the ducts.

  2. Endoderm (cloaca) of the urogenital sinus

    • Forms the vaginal plate, which later canalizes to form the lower vagina.

  3. As the ducts fuse and move medially, they pull the peritoneum with them, forming the broad and ovarian ligaments.

    • The broad ligament becomes the support structure for the uterus, fallopian tubes, and ovaries.

External Genitalia Formation

  • (A) Initial State: Male & female external genitalia are initially indistinguishable. Consists of:

    • Labioscrotal folds

    • Urogenital folds

    • Genital tubercle

  • (B) Male Differentiation: Dependent on dihydrotestosterone.

    • Urogenital folds fuse; encloses phallic portion of urogenital sinus to form penile urethra.

    • Genital tubercle elongates to form shaft & glans of penis.

    • Labioscrotal folds fuse to become scrotum.

  • (C) Female Differentiation: In females, the absence of dihydrotestosterone causes differential growth & morphogenesis of external genitalia.

    • Genital tubercle bends inferiorly to forms clitoris.

    • Urogenital folds remain separate to form labia minora.

    • Labioscrotal folds form labia majora.

Gonadal Development Factors & Cells

  • This section provides an overview of factors such as Sf1, Fgf9, Wnt4, PdgfA, Dhh, Retinoic Acid, Testosterone, Estrogens, and cells including Germ cells, Coelomic epithelium, Myoid cells, Pre-Sertoli cells, Leydig cells, Sertoli cells, Follicle precursor cells, Follicle cells, Thecal cells, and Oocytes which contributes to Testis and Ovary development.