Močopohlavní systém - Vývoj Aleš Hampl cloaca Močopohlavní systém – Celkový obraz Močopohlavní systém – Připomenutí Močopohlavní systém – Intermediární mesoderm Močopohlavní systém – Časné formy ledvin- Pronephros Recapitulation of three stages of evolution of kidneys in a cranial to caudal sequence: •pronephros •mesonephros •metanephros Nephrotomes Nephric duct Nephrotomes •at about day 22 in cervical part of nephrogenic cord •7 to 10 groups of epithelial cells •connect to primary nephric duct •non-functional •disappear by day 28 pronephros primary nephric duct https://syllabus.med.unc.edu/courseware/embryo_images/unit-genital/genital_gifs/genital003-1a.gif https://syllabus.med.unc.edu/courseware/embryo_images/unit-genital/genital_gifs/genital003-2.gif The lumen of each nephrotome opens into the primary nephric duct as well as into the body cavity. Glomeruli form as small vessels extend from the dorsal aortae. Mouse D9 – equivalent to human D27 Močopohlavní systém – Časné formy ledvin- Pronephros Močopohlavní systém – Časné formy ledvin- Mesonephros Mesonephros •caudal continuation of nephrogenic cord •thoracolumbar region •unsegmented intermediate mesoderm •mesonephric ducts (paired) – Wolffian ducts •exkreční kanálky – open individually into m. duct •36 to 40 m. tubuli in total (on one side) •some filtration – mesonephric unit •mesonephros is most prominent when metanephros start to shape •then they diasappear fast •mesonephric ducts persist in males Močopohlavní systém – Mesonephros – Další pohled Močopohlavní systém – Definitivní ledviny - Metanephros Ureterový pupen + Metanephrogennní blastém (mesenchyme) Develop since week 5 Branching and Elongation 14 to 15 x Močopohlavní systém – Definitivní ledviny - Metanephros 325_2 Opakované větvení ureterového pupenu: •ureter •pelvis •calyces (major + minor) •collecting tubuli (1 to 3 millions) Uriniferous tubule = The functional unit of the kidney Ducts of Bellini Area cribrosa Minor calyx Cortex Medulla 1 to 1.4 milllions of nephrons in one kidney Nephrons X Collecting tubules Different embryological origin renal corpuscle Močopohlavní systém – Metanephros - Nefrony •arched ampulous endings of ureteric ducts (collecting tubuli) – capping by condensed mesenchyme •part of the cap cells differentiate into nephrogenic vesicle •vesicles elongate •vesicles open to the collecting tubulus on one end •distal from the ducts, the cells of elongating vesicles polarize and form lumen and basal lamina •precursors of endothelia grow into this area - glomerulus •endothelia connect to branches of dorsal aorta – gromerular circulation •production of urine since week 10 Močopohlavní systém – Metanephros - Nefrony •about 15 successive generations of nephrons in peripheral zone of kidney •outermost nephrons are less mature Cortical nephrons Juxtamedulary nephrons Močopohlavní systém – Metanephros - Nefrony EMBRYONIC KIDNEYS IN PIG Močopohlavní systém – Definitivní ledviny - Metanephros 5 weeks 6 weeks 8 weeks • ventral outpocketing of the hindgut • sac-like structure (respiration) • in umbilical cord • proximal part – URACHUS – continuos with bladder • URACHUS – transforme to Lig. umbilicale medianum 4.5 weeks Močový systém - Měchýř Kloaka = terminal part of the zadní střevo + allantois Simus urogenitalis Septum urogenitale Canalis analis Membr. urogenitalis Membrana analis Perineum Cloaca Močový systém – Měchýř + Uretery + Uretra •alantois expands - urinary bladder •initially bladder is continuos with alanotois – then obliteration – urachus – Lig. umbilicale medianum •caudal portions of mesonepric ducts become absorbed by the bladder wall – separation – ureters + ejaculatory ducts Posterior view Urachus Primitive urethra Ureter Ureter Trigone Ejaculatory duct Močový systém – Vrozené anomálie 1. Agenesis 2. Duplication 3. Anomalies of shape 4. Abnormal of position 5. Congenital polycystic kidney Horseshoe kidney Pohlavní systém Pohlavní dimorfismus – individual can only have one type of genital organs Genetic determination: •Heterogametic (XY) – male •Homogametic (XX) - female Indifferent stage Differentiation into individual sexes 7th week Fertilization = genetic gender established (Barr body) Pohlavní systém – 7 weeks at indifferent stage Gonads External genitalia Sertoli cells Leydig cells No MIS No Testosterone Sexual Determination Sexual Differentiation Sry gene – Sox family TF – on short arm of Y chromosome Default pathway Y chromosome decides XXY – male X0 - female Pohlavní systém – Sry gen SRYtranslocation3 Pohlavní systém – Sry gen Pairing of X and Y chromosomes in pseudoautosomal region during meiosis Rare crossing-over causes translocation of SRY to X chromosome: XY females or XX males Vývoj urogenitálního systému - 34 Pohlavní systém – Primordiální germinální buňky File:Stage9 bf2-primordial germ cell region.jpg http://a.abcam.com/ps/datasheet/Images/13/ab13840/ab13840_5.jpg PGC - large spherical cells Primordial germ cells (PGC) • first recognizable at day 24 • from epiblast-derived extraembryonic msoderm • few cells among endodermal cells of the yolk sac • they migrate through the dorsal mesentery of the hindgut • migrate towards genital rigdes (plicae genitales) • proliferate during migration • reach (1-2 thousands) genital ridges on week 6 of gestation Males PGC stop dividing Females PGC enter meiosis X decided by somatic cells in the genital ridges FemGen006 Pohlavní systém – migrace PGC do základů gonád Pohlavní systém – základ gonád Steroidogennní mesoderm along the ventromedial border of the mesonephros Kaudální oblast = Pohlavní lišty Vývoj urogenitálního systému - 33 cells of coelomic epithelium + cells from mesonephric ridge Week 4 – Th6 to S2 cranial + caudal parts involute Week 6 – L3 to L5 become populated by PGC at week 6 Vývoj urogenitálního systému - 35 Pohlavní systém – indiferentní gonáda (týden 6) Medulární provazce Pohlavní systém – Diferenciace varlat Late 6th week Cord cells differentiate to Sertoli cells (meiosis-inhibiting factor, anti-mullerian substance, androgen binding factor) Tunica albuginea develops (sets barrier between coelomic epithelium and testis cords) Cord cells form seminiferous tubuli, tubuli recti, and rete testis Rete testis joints ductli efferentes that are derived from mesonephric ducts (5th to 12th) Week 8 to 18 Leydig cells develop and function in developing testis •from coelomic epithelia and mesonphros •produce testosteron •support development of Wolfian (mesonephric) duct •support development of external genitalia Vývoj urogenitálního systému - 37 •PGC concentrate in the cortical region • •PGC proliferate (max until week 22) and then enter meiosis – arrest in prophase • •Ovarian follicles develop (somatic cell contribution is not understood) • •Transient rete ovarii develops in medullary region • •Medulla contains connetive tissue and vasculature derived from mesonephros Pohlavní systém – Diferenciace vaječníků FemGen011 Pohlavní systém – Vývodné cesty – Indiferentní stádium Paramesonephric duct Develops at days 44 to 48 Cranially opens to coelomic cavity Week 7 Wolffian Mullerian Pohlavní systém – Vývodné cesty – Muži Mesonephric ducts (Wolffian) •Ductus epididymis •Ductus deferens •Ductus ejaculatorius •Seminal vesicle Paramesonephric ducts (Mullerian) regresses in week 8 (anti-M hormone) •Appendix testis (cranial part) •Utriculus prostaticus (caudal part) • Mesonephros •Ductuli efferentes •Paradidymis (under the testis, nonfunctional) • Pohlavní systém – Sestup varlat Gubernaculum – originates from caudal portion of genital ridge „Prerequisites + driving forces“ for the descent of testes: •testes enlargement •atrophy of mesonphros – allows for caudal movement •tension of gubernaculum •atrophy of paramesonephric ducts – move to unquinal canal •enlargement of processus vaginalis peritonei (6th month) •increased intraabdominal pressure ? By 26 weeks •the testes have descended retroperitoneally to the deep inguinal rings During 26th week •final descent through the inguinal canals into the scrotum – 2 to 3 days NOTES More than 97% of full-term newborn males have both testes in the scrotum During the first 3 months after birth, most undescended testes descend into the scrotum Spontaneous testicular descent does not occur after the age of one year Vývoj urogenitálního systému - 49 Processus vaginalis obliterated NORMAL Remaing cyst = Hydrocele ABNORMAL Remanining connection ABNORMAL Pohlavní systém – Sestup varlat Mesonephric ducts (Wolffian) regresses (absence of testosterone) •Gartners cyst (caudal part) Paramesonephric ducts (Mullerian) involutes in week 8 •Uterine tubes (falopian t.) •Uterus •Vagina Mesonephros (+Mesonephric duct) •Epoophoron (appendix of ovary) •Paraophaoron Vývoj urogenitálního systému - 40 Pohlavní systém – Vývodné cesty – Ženy genitál5 Pohlavní systém – Vývodné cesty – Ženy Vývoj urogenitálního systému - 43 Dorsal view Lateral view Paramesonephric (Mullerian) ducts fuse to form uterus and upper 1/3 of vagina Pohlavní systém – Vývodné cesty – Ženy Vaginální ploténka M14879-016-f037 Pohlavní systém – Vývodné cesty – Anomálie They are derived from a complex mesodermal tissue located around cloaca. Week 8 Week 6 to 8 Genitální výběžek – Phallus Uretrální řasy – Plicae urogenitales Genitální valy – Tori genitales Orificium urogenitale primitivum ohraničeno: HORMONE-INDEPENDENT Pohlavní systém – Zevní pohl. orgány – Indiferentní stádium Week 9 to 13 Weeks 12 + 13 are particularly critical = fůze uretrálních řas Genitální valy Genitální výběžek Uretrální řasy Clitoris Labia minora Labia majora Penis Urethra Scrotum MUŽ ŽENA Pohlavní systém – Zevní pohl. orgány – dimorfismus M14879-016-f028 Influenced by dihydrotestosterone Influenced by testosterone Pohlavní systém – Zevní pohl. orgány – Muži Genital tubercle elongates – penis (phallus) Genital swellings enlarge – scrotum Genital folds form the lateral walls of the urethral groove Genital folds form the spongy urethra Ventral epithelium of genital folds – urethra proper Corpora cavernosa develop from mesenchyme M14879-016-f035 Scrotal raphe (šev) Urethral raphe (šev) Anus Scrotum Uretrální ploténka Fůze uretrálních řas + lumen – uretra vytvořena Uretrální rýha Pohlavní systém – Zevní pohl. orgány – Muži •ectodermal ingrowth forms a cellular ectodermal cord Penis body Ektodermální čep Glans penis Spongy urethra Coronary groove Surface ectoderm Spongy urethra Spongy urethra Developing septum Vyůstění močové trubice Distal part of spongy urethra Předkožka Pars glandis urethrae •the cord grows towards the root of the penis to meet the spongy urethra •the cord canalizes •circular ingrowth of ectoderm occurs at the periphery of the glans penis (week 12) •circular ingrowth breaks down forming prepuce (for some time adherent to the glans penis, hard to retract at birth) Pohlavní systém – Zevní pohl. orgány – Ústí uretry M14879-016-f038 Normal midline raphe Raphe off center Pohlavní systém – Zevní pohl. orgány – Hypospadie urethra and vagina open into vestibule = from urogenital sinus urethra develops from the more cranial part of urogenital sinus – equivalent to prostatic urethra Pohlavní systém – Zevní pohl. orgány – Ženy Thank you for your attention ! Questions and comments at: ahampl@med.muni.cz http://clinicalgate.com/wp-content/uploads/2015/03/B978044306684950086X_gr13.jpg