Urinary system development. Male ( ) and Female ( ) Reproductive Systems Development

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1 Urinary system development Male ( ) and Female ( ) Reproductive Systems Development

2 Urogenital system develops from mesodermal uro-genital ridge (intermediate mesoderm) development of male and female genital systems are closely integrated with primitive urinary system Urinary system development Three kidney systems develop in craniocaudal sequences during intrauterine life in humans: pronephros mesonephros metanephros, the definitive kidney or permanent kidney

3 Pronephros At the beginning of the fourth week 7 to 10 solid cell groups of intermediate mesoderm in the cervical region. The groups form nephrotomes vestigial excretory units The pronephric system is disappeared by the end of the fourth week. Pronephros is nonfunctional organ in human

4 Mesonephros Mesonephroi and mesonephric ducts are derived from intermediate mesoderm, lie caudal to pronephroi Mesonephroi begin development late in fourth week, during regresion of pronephros system the first excretory tubules appear. Mesonephros consists of renal corpuscles (capilaries branching of aorta and mesonephric tubule, which open into the mesonephric duct, a continuation of the pronephric duct

5 Mesonephros In the second month the mesonephros large ovoid organ on each side of the midline. Mesonephroi proper degenerate, mesonephric ducts (Wolffian ducts) have derivatives in males (the epididymis, vas deferens, seminal vesicles)

6 Metanephros (the third urinary organ) Permanent kidney Begins development in the fifth week - secretory units develop from metanephric mesoderm Collecting ducts develop from the ureteric bud and the metanephric mesoderm The ureteric bud gives rise to the ureter, the primitive renal pelvis, the major and minor calyces, and 1 milion to 3 milion collecting tubules. Each of collecting tubule has metanephric cap renal vesicles + capillaries = glomeruli Collecting tubules with their glomeruli form nephrons or excretory units. Proximal end of nephrons forms Bowman s capsule, distal end forms proximal convoluted tubule, Henle s loop, and distal convoluted tubule The definitive kidney becomes functional organ near 12th week Urine produced and released into amniotic fluid At the birth the kidneys have a lobulated structure, the lobulation disappears during the infancy

7 Urinary system development Summary Permanent kidney Disappeared The proper disappears Mesonephric ducts or Wolffian ducts The epididymis, vas deferens

8 Congenital anomalies During the long process of renal development, problems can arise at any stage: Renal dysplasias and agenesis (1) internal structures do not develop normally or lack the organ Abnormal rotation and ectopic kidneys Horseshoe kidney (2) Congenital polycystic disease (3) (1) (2) (3) Multicystic dysplastic kidney

9 46, XY Genital system development 46, XX Male Female The sex of embryos is determinated genetically at the time of fertilization zygote contains XY chromosomes, zygote XX chromosomes. The key to sexual dimorphism is the Y chromosome, which contains the SRY (sex-determining region on Y) gene on its short arm SRY protein is testis-determining factor (TDF), under its influence male development occurs In the absence of the protein female development is established. The expression of many genes In male, the hormones are synthesized and released in strictly defined concentration and time Gonadal development is limited in the absence of primordial germ cells (gonocytes) They are formed among the endodermal cells of yolk sac wall, migrate along the mesenthery of the hindgut and repopulate rudiment of gonads in the sixth week

10 46, XY Male 46, XX Female The developing gonads do not acquire male and female morphological characteristics until seventh week of development Two stages of gonads development indifferent gonad - no morphological differences (no gonocytes) bipotential gonad differentiation process of gonads is different in the both sexes (Y - SRY protein) The testis male gonad and the ovary female gonad are derived from cells of three germ layers: mesoderm the coelomic epithelium (mesothelium) Sertoli cells mesenchyme the tissue underlying the mesothelium Leydig cells endoderm of yolk sac primordial germ cells (gonocytes)

11 4 th week of development, at about the 10 th thoracic level, mesodermal epithelial cells (mesothelium) proliferate and cells of mesenchyme condensate to form a pair longitudinal genital or gonadal ridges just medial to developing of mesonephroi. Shortly before and during arrival of gonocytes, the mesodermal cells penetrate the mesenchyme, where they form a number of irregularly shaped cords primitive sex cords In and embryos these cords are connected to the surface epithelium (indifferent gonad)

12 Testis - Male gonad development 7th week The differentiation process In embryo genetically male, primordial germ cells carry XY chromosome complex (SRY protein). The primitive sex cords continue to proliferate The cells penetrate into the medulla to form testis or medullary cords Toward the hilum, cells of the cords form tiny tubules rete testis The medullary cords loss the contact with surface epithelium A dense layer of fibrous connective tissue the tunica albuginea, separates the testis cords from the surface epithelium Medullary cords Rete testis

13 Testis - Male gonad development The testis cords become horseshoe shaped and are connected with the rete testis The testis cords Sertoli cells (the mesodermal surface epithelium) and primitive germ cells (endoderm of yolk sac wall) Future seminiferous tubules Red gonocytes Mesenchyme Interstitial tissue

14 Male gonad development Interstitial Leydig cells derived from mesenchyme of the genital ridge, lie between the testis cords they begin development shortly after differentiation of ridge cords by the eighth week of gestation they begin production of testosterone at the time testis is able to influence sexual differentiation of the genital ducts and external genitalia (T DHT). Leydig cells (between the testis cords)

15 Ovary - Female gonad development 10 th week The differentiation process No chromosome Y (XX sex chromosome complex ), no SRY protein primitive sex cords dissociate into irregular cell clusters the clusters with primitive germ cells occupy the medullary part of ovary they disappear and are replaced by vascular stroma the ovarian medulla The surface epithelium continues to proliferate and the second generation of cords, cortical cords is formed The cortical cords remain close to the surface In the fourth month the cords split into the isolated cell clusters The cells surround one primitive germ cells (primordial ovarian folicles) Germ cells develop into the oogonia, surrounding cells form folicular cells granulosa cells Oogonia endoderm of yolk sac wall, follicular cells mesodermal surface epithelium

16 Differentiation of the gonad-associated sex ducts Müllerian duct (blue) develops in females (middle image) and degenerates I n males (bottom) Originally both mesonephric Wolffian ducts (male specific) and paramesonephric Müllerian ducts (female specific) are present in both sexes. Müllerian ducts are newly produced ducts as invagination of mesodermal epithelium on the anterolateral surface of genital ridges. In males, the Müllerian duct degenerates due the action of AMH/MIS Antimüllerian hormone/müllerian inhibiting substance (secretory product of Sertoli cells) and Wolffian duct will differentiate into the epididymis, vas deferens, seminal vesicles. In the females the Müllerian ducts will differentiate into the oviducts, uterus and upper part of the vagina, while Wolffian ducts are disappeared in the absence of testosterone.

17 Hormonal control of male sex differentiation T 5α- reductase DHT Wolffian ducts are maintained by testosterone (T) produced by Leydig cells efferent ductules, the epididymis, seminal vesicle, vas deferens, ejaculatory duct. Müllerian ducts regress under the influence of AMH/MIS (Antimüllerian hormone/müllerian inhibiting substance) produced by fetal Sertoli cells The urogenital sinus and external genitalia development - under control of DHT, produced from testosterone the enzyme 5α-reductase.

18 Hormonal control of female sex differentiation Ovaries & external genitalia Estrogens including maternal and placental sources Paramesonephric ducts stimulated (uterine tube, uterus, vagina - upper portion) External genitalia stimulated (labia, clitoris, vagina - lower portion)

19 Descent of the testes During embryonic and fetal life, testes descend from their original position to the scrotum The descent of the gonad depends on a ligamentous cord the gubernaculum Hormonal regulation left sided Cryptorchidism

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21 Hypospadias Hypospadias is a condition that affects approximately 1 in 200 boys. The problem manifests itself as a defect of the opening of the urethra. Normally the urethra passes through the centre of the penis to open in the middle of the head of the penis known as the glans. However, the opening may be found on the under surface of the penis.

22 Epispadias This male infant was born with bladder exstrophy. The bladder mucosa is everted and lies on the abdomen. Both ureteric orifices lie on the exstrophic bladder. Notice that the penis is shortened and that there is no urethral meatus. His urethra is actually a plate of deep red mucosa lying on the dorsal penis. This is called epispadias.

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24 Main abnormalitis of the uterus and vagina Uterus didelphys (double uterus) with double vagina Uterus bicornis bicollis Uterus bicornis unicollis Normal uterus Uteres unicornis Uterus unicornis with rudimentary horn Uterus septum Uterus arcuatus