LESSON 9 DEVELOPMENT OF GENITOURINARY SYSTEM Objectives By the end of this lesson, you should be able to: - 1. Describe the origin of the urogenital system 2. Describe the development of the male and female urinary system 3. Describe the development of the male and the female gonads 4. Describe the development of the male and the female accessory structures of reproduction 5. Describe the development of the male and the female external genitalia

Introduction The urogenital system can be divided functionally into the urinary system and the genital system. • Embryologically and anatomically, however, they are closely connected. • The urogenital system develops from the intermediate mesoderm which extends along the dorsal body wall of the embryo. • The intermediate mesoderm later loses its connection with the somites and forms a longitudinal elevation of the mesoderm called the urogenital ridge. • Part of the urogenital ridge giving rise to the urinary tract is known as the nephrogenic cord. • The medial part of the urogenital ridge forms the gonadal (genital) ridge. • The mesothelial lining of the peritoneal cavity and the endoderm of the urogenital sinus also take part in the development of the urogenital system.

Urogenital ridge 1. Gut 2. Gonad 3. Bowman's capsule 4. Mesonephric duct 5. Excretory tubule of mesonephros 6. Glomerulus 7. Mesentery

URINARY SYSTEM KIDNEY • During the intrauterine life, three separate excretory systems arise successively. 1. The pronephros - This is nonfunctional and undergoes complete regression soon after its formation. 2. The mesonephros - serves as a temporary excretory organ. The body of the mesonephros undergoes degenerative changes, but caudal parts of the mesonephric tubules and mesonephric duct persist in the male. 3. The metanephros – This is a definitive structure

Pronepros 1. Nephrotomes 2. Pronephric tubuli 3. Pronephric duct Mesonepros 1. Excretory units 2. Mesonephric duct 3. Nephrogenic cord Metanephros 1. Cloaca 2. Metanephric mesoderm 3. Ureteric bud

PRONEPHROS The pronephros appears early in the fourth week as segmentally arranged cell (nephrotomes) and tubular (pronephric tubuli) structures in the cervical region of the intermediate mesoderm. The pronephric tubules open into the intraembryonic coelom (coelomic cavity), while the pronephric duct runs caudally and opens into the cloaca. By the beginning of the 5th week, the regression of the vestigial nephrotomes is complete.

Pronepros 1. Pronephric tubule 2. Glomerulus 3. Dorsal aorta 4. Splanchnic mesoderm 5. Somatic mesoderm 6. Intraembryonic cavity 7. Neural tube 8. Yolk sac 9. Endoderm

MESONEPROS • Late in the 4th week, caudal to the rudimentary pronephros. • The nephrogenic cord, from the first thoracic to the third lumbar segment, differentiates into mesonephric vesicles which elongate to form an S-shaped loops (tubules). • At their medial end, Bowman's capsule forms a mesonephric (renal) corpuscle together with the glomerulus. • At the opposite end, the tubules enter the mesonephric (Wolffian) duct. • Some parts of the mesonephric (Wolffian) duct do not completely disappear, but they persist in the male as the epididymis duct, ductus deferens, seminal vesicle and ejaculatory duct. • Also, some of the mesonephric tubules near the gonad persists in the male as the efferent ductules of the testis.

Mesonepros 1. Gut 2. Gonad 3. Bowman's capsule 4. Mesonephric duct 5. Excretory tubule of mesonephros 6. Glomerulus 7. Mesentery Mesonephros and developing gonad 1. Gonad 2. Interstinal loop 3. Mesonephric duct 4. Neural tube 5. Mesonephros

METANEPHROS • The definitive kidney or metanephros originates from two mesodermal rudiments: the ureteric bud (metanephric diverticulum) and the metanephric mesoderm (metanephrogenic blastema). • The collecting system develops from the ureteric bud, a dorsal outgrowth of the mesonephric (Wolffian) duct close to its entrance into the cloaca. • The bud penetrates the metanephric mesoderm forming the ampulla, which undergoes a series of repeated bifurcations. • The ureteric bud gives rise to the ureter, renal pelvis, major and minor calyces and collecting tubules within the kidney.

Development of the renal pelvis • Metanephric mesoderm develops from the sacral portion of the nephrogenic cord. • Under the inductive influence of the ampulla, the metanephric mesoderm differentiates into renal vesicles and than into S-shaped tubules. • The tubules give rise to the excretory parts of the metanephros, called nephrons. • A nephron consists of the Bowman's capsule, the proximal convoluted tubule, the loop of Henle, and the distal convoluted tubule. Development of the renal pelvis 1 . Metanephric mesoderm 2 . Ureteric bud

Development of the renal pelvis 1. Metanephric mesoderm 2. Ureteric bud 3. Pelvis 4. Major calyx

Development of the renal pelvis 1. Metanephric mesoderm 2. Ureteric bud 3. Minor calyses 4. Pelvis

Development of the nephron 1. Metanephric tissue cups 2. Ampulla 3. Collecting tubule 4. Metanephric mesoderm

Development of the nephron 1. Metanephric tissue cups 2. Cell clusters 3. Renal vesicle 4. Collecting tubule

Development of the nephron 1. Proximal convoluted tubule 2. Bowman's capsule 3. Metanephric mesoderm 4. Collecting tubule

Development of the nephron 1. Bowman's capsule 2. Distal convoluted tubule 3. Collecting tubules

Development of the nephron 1. Distal convoluted tubule 2. Glomerulus 3. Collecting tubules 4. Proximal convoluted tubule 5. Henle's loop 6. Bowman's capsule Development of the metanephros

• The metanephros originates in the pelvic region. • Between the 6th to 8th week of the development, the metanephros ascends to the lumbar region, because of the disproportionate growth of the lumbar and sacral region. • During the kidney ascent to the abdominal level it rotates medially almost 90º. • Initially, the kidney hilum faces ventrally, but is finally directed anteromedially after the ascent and rotation. Ascent of the kidney 1. Urogenital ridge 2. Genital ridge 3. Mesonephric duct 4. Mesonephros 5. Gonad 6. Metanephric tissue 7. Ureter 8. Cloacal membrane 9. Cloaca 10. Allantois 11. Urorectal septum 12. Tail

Ascent of the kidney 1. Mesonephric duct 2. Mesonephros 3. Gonad 4. Metanephros 5. Ureter 6. Cloacal membrane 7. Cloaca 8. Urorectal septum 9. Urogenital sinus 10. Anorectal canal 11. Tail

Ascent of the kidney 1 . Ureter 2 . Metanephros 3 . Gonad 4 . Mesonephric duct 5 . Anal membrane 6 . Urogenital membrane 7 . Perineal body 8 . Bladder 9 . Rectum

URETER, URINARY BLADDER AND THE URETHRA • The ureters develop from the caudal portion of the ureteric bud. • The urinary bladder and urethra are derived from the primitive urogenital sinus (a ventral part of the cloaca) and adjacent splanchnic mesenchyme. • The cloaca, the terminal portion of the hindgut is divided into the dorsal primitive rectum and ventral primitive urogenital sinus by the growth of the urorectal septum. • The same septum also divides cloacal membrane into the urogenital membrane anteriorly, and the anal membrane posteriorly.

Development of urogenital sinus 1. Mesonephric duct 2. Mesonephros 3. Gonad 4. Metanephros 5. Ureter 6. Cloacal membrane 7. Cloaca 8. Urorectal septum 9. Urogenital sinus 10. Anorectal canal 11. Tail

Formation of the urogenital sinus 1 . Ureter 2 . Metanephros 3 . Gonad 4 . Mesonephric duct 5 . Anal membrane 6 . Urogenital membrane 7 . Perineal body 8 . Bladder 9 . Rectum Development of the urinary bladder

• The urogenital sinus gives rise to the urinary bladder, which is cranially continuous with allantois (later urachus) and caudally with the urethra. • During division of the cloaca the caudal portions of the mesonephric ducts are incorporated into the wall of the urinary bladder thus forming the trigone of the bladder. • The ureters and mesonephric ducts with time obtain the separate entrances into the urinary bladder. • In the male, the pelvic part of the urogenital sinus gives rise to the prostatic and membranous part of the urethra. • The penile urethra is partly formed by the closure of urethral folds, while its most distal portion is formed by an inward penetration of ectodermal cells on the tip of the glans. Development of the bladder and ureters 1. Ureter 2. Mesonephric duct 3. Urinary bladder

Development of the bladder and ureters 1. Ureter 2. Mesonephric duct 3. Urinary bladder

GENITAL SYSTEM • The genital system consists of the gonads, associated genital ducts and external genitalia. • Although the genetic sex of an embryo is determined at the time of fertilization, male and female genital systems are similar until the 7th week of the development (indifferent gonads stage). GONADS The gonads (testes and ovaries) are derived from three sources: - 1. The mesothelium (coelomic epithelium) lining the posterior abdominal wall 2. The underlying gonadal ridge mesenchyme 3. The primordial germ cells (precursors of spermatogonia or oogonia).

Urogenital ridge 1. Gut 2. Gonadal ridge mesenchyme 3. Bowman’s capsule 4. Excretory tubule of mesonepros 5. Longitudinal mesonephric duct 6. Glumerulus 7. Mesentry Development of the gonads • The primordial germ cells first appear in the wall of the yolk sac in the 6th week and migrate along the dorsal mesentery of the hindgut to the genital ridges. • Genital ridges form a thickened area comprising mesothelium and underlying mesenchyme on the medial side of the mesonephros. • Epithelium of the genital ridge proliferates and penetrates the underlying mesenchyme, forming the primitive sex cords. Indifferent gonad 1. Coelomic epithelium (mesothelium) 2. Primitive sex cords 3. Primordial germ cells 4. Dorsal mesentery 5. Mesenchyme

DEVELOPMENT OF TESTIS • The primitive sex cords continue to proliferate and penetrate deep into the medulla to form the testis (medullary) cords and rete testis. • Later these testis cords lose contact with the surface epithelium because of the formation of a dense connective tissue capsule around the testis, the tunica albuginea. • The sex cords are composed of supporting Sertoli cells, derived from the mesothelium (coelomic epithelium) and spermatogonia, derived from the primordial germ cells.

Development of the testis cont… • The interstitial cells of Leydig are derived from the genital ridge mesenchyme. • The primitive sex cord gives rise to the seminiferous tubules, rete testis and tubuli recti. • The efferent ductules derived from the remnants of the mesonephric tubules connect the rete testis to the derivatives of the mesonephric duct (epididimis, ductus defferens, seminal vesicle and ejaculatory duct).

Development of the testis 1. Tunica albuginea 2. Degenerating mesonephric tubule 3. Rete testis cords 4. Mesonephric duct 5. Paramesonephric duct 6. Testis cords 7. Mesothelium

DEVELOPMENT OF OVARIES • The ovary becomes differentiated later than the testis. • The tunica albuginea does not become a prominent structure, while the primitive sex cords undergo medullary degeneration. • In the 7th week, the surface epithelium proliferates and gives rise to a second generation of cords, the cortical cords. • Later, these cords split into cell clusters that develop into follicles with granulosa cells surrounding a central oogonium (derived from the primordial germ cells). • The oogonia subsequently proliferate and differentiate into primary oocytes. • Thecal cells that surround the follicles derive from the mesenchymal stroma of the gonadal ridge.

Development of the ovary 1. Cortical cords 2. Degenerating mesonephric tubule 3. Mesonephric duct 4. Paramesonephric duct 5. Degenerating medullary cords 6. Surface epithelium

DEVELOPMENT GENITAL DUCT • Both sexes have initially two pairs of genital ducts: the mesonephric (Wolffian) ducts and the paramesonephric (Müllerian) ducts. • The paramesonephric (Müllerian) duct arises as a longitudinal invagination of the coelomic epithelium on the anterolateral surface of the the urogenital ridge and empties into the urogenital sinus. • It can be divided into three parts: a) the cranial part which opens into coelomic cavity b) the horizontal part which crosses the mesonephric duct c) the caudal part which fuses with the same duct from the other side. The cranial parts develop into the uterine tubes while the caudal fused parts develop into the uterus, cervix and one third of the vagina. The surrounding layer of the mesenchyme forms the myometrium and perimetrium.

Formation of the female genital ducts 1. Abdominal ostium of uterine tube 2. Paramesonephric tubercule 3. Uterine canal 4. Paramesonephric duct 5. Cortical cords of ovary 6. Mesonephric duct 7. Mesonephros DEVELOPMENT OF THE VAGINA

• When the paramesonephric ducts reach the urogenital sinus, two evaginations (sinovaginal bulbs) proliferate and form a solid vaginal plate. • By the 5th month, this plate is completely canalized. • Thus, the vagina has a dual origin: - – upper one third derives from the paramesonephric duct – lower two thirds from the urogenital sinus. Development of the uterus and vagina 1. Symphysis 2. Uterine canal 3. Urinary bladder 4. Sinovaginal bulbs 5. Genital tubercle 6. Perineal body 7. Anus

Development of the uterus and vagina 1. Urethra 2. Urinary bladder 3. Uterus 4. Fornix 5. Vagina 6. Hymen Further development of the genital ducts • The paramesonephric duct in the male degenerates, except for a small portion known as the appendix testis and utriculus prostaticus. • The mesonephric (Wolffian) duct develops by the canalization of a solid mass of cells in the urogenital ridge and empties into the urogenital sinus lateral to the paramesonephric duct orificies. • It gives rise to the ductus epididymis, seminal vesicle, ductus deferens and ejaculatory duct. • The mesonephric duct in female regresses, but may persist as the appendix vesiculosa, paroophoron and Gartner's duct. • In both sexes, a branch of mesonephric duct forms the ureteric bud. Development of the male genital ducts 1. Mesonephric tubules 2. Rete testis 3. Mesonephric duct 4. Paramesonephric tubercule 5. Paragenital tubules 6. Testis cords 7. Tunica albuginea

EXTERNAL GENITALIA • In the indifferent stage the external genitalia are made up of a small genital tubercle, urethral folds, and genital (labioscrotal) swellings. • Later, these swellings form scrotal swelling in the male and the labia majora in the female. • In the female, the genital tubercle forms the clitoris, urethral folds develop into the labia minora, while the genital swelling forms the labia majora. • In the male, the genital tubercle elongates into the glans penis, while the urethral folds fuse to form the corpus spongiosum of the penis. • The genital swellings subsequently unite into a single scrotum.

Development of the external genitalia 1. Anal membrane 2. Genital (labioscriotal) swelling 3. Genital tubercle 4. Urethral folds 5. Anal fold 6. Urogenital membrane

Development of the external genitalia 1. Scrotal swelling 2. Urethral folds 3. Perineum 4. Anal fold 5. Phallus 6. Urethral groove 7. Labia majora 8. Clitoris 9. Labia minora Conclusion

 Origin of the urogenital system  Development of the male and female urinary system  Development of the male and the female gonads  Development of the male and the female accessory structures of reproduction  Development of the male and the female external genitalia