Transcript Normal Development of the Urogenital System

Normal Development of the
Urogenital System
Christi Hughart, D.O.
Kidney Development
• 3 embryonic kidneys (from intermediate
mesoderm)– Pronephros- transient (week 3-5), nonfunctional, 5-7
paired segments.
– Mesonephros- transient (week 4- month 4), excretory
organ while metanephros begins development. Form
renal corpuscles.
• Formation of nephric ducts/wolffian ducts (controlled by
Pax2, Lim 1) precedes development of mesonephric tubules.
• Small number of elements from mesonephros persist to form
reproductive tract.
– Males- efferent ductules of testes, epididymis and vas- wolfian
origin.
– Females- nonfunctional mesosalpingeal structures.
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– Metanephros- definitive kidneys
• Form as ureteric buds (from distal end of nephric duct) (RETGDNF-GFR alpha 1 pathway).
• Penetrates metanephric mesenchyme at 28 days to begin
nephron formation- lobulated appearance.
– Autosomal recessive polycystic kidney disease- (1/5,000)
progressive, cysts form from collecting ducts. (RF in infancy or
childhood).
– Autosomal dominant polycystic kidney disease- (1/500-1/1,000)
cysts form from all segments of nephron. (RF in adulthood).
• Metanephric mesoderm forms nephron or excretory unit
(glomerulus, proximal tubule, loop of Henle, distal tubule)form from metanephric mesenchyme. Develop in stages I-IV.
– Older nephrons on inner part of kidney, newer at periphery.
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• Collecting system (collecting ducts, calyces, pelvis, ureter)formed from ureteric bud.
– Week 6= 16 branches, week 7= minor calyces formed, week 32=
1-3 million branches.
– Duplication of the ureter- due to early splitting of the ureteric
bud.
– Ectopic ureter- one ureter opens into bladder and other into
vagina, urethra, or vestibule.
– Multicystic dysplastic kidney- numerous ducts surrounded by
undifferentiated cells- nephrons fail to develop and ureteric bud
fails to branch- collecting ducts never form» may cause involution of kidney or renal agenesis (also
occurs if ureteric bud fails to contact metanephric
mesoderm).
» B/L renal agenesis (1/10,000)- Potter sequence- anuria,
oligohydramnios, hypoplastic lungs (other associated
anomalies).
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• Definitive kidney functional at 12 weeks- urine
passed into amniotic cavity and mixes with amniotic
fluid- fluid swallowed by fetus and recycles
(placenta excretes waste).
• Renal maturation continues after birth but
nephrogenesis is complete before birth.
Renal Ascent
• Week 6-9- ascend to lumbar site below adrenals.
– Thought to be due to differential growth of lumbar and
sacral regions of embryo.
– Vascularized by succession of transient aortic branchesdegenerate- final pair remaining is renal arteries (may
have accessory renal arteries if some persist).
– Horseshoe kidney (1/600 births)- inferior poles fuse,
across ventral side of aorta, fused lower pole stuck
under IMA.
– Cross-fused ectopy- one kidney fuses to contralateral
one and ascends to opposite side.
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Renal Vascular Development
• Angiogenic Hypothesis- derived from
branches off aorta and other pre-existing
extrarenal vessels.
• Vasculogenic Hypothesis- originate in situ
from vascular progenitor cells (VEGF).
Bladder (Urogenital Sinus)
• 3rd week- cloacal membrane bilaminar (endoderm and
ectoderm).
• 4th week- neural tube and tail grow dorsally and caudally
to project over cloacal membrane (embryo folding)cloacal membrane now ventral.
• 5th-6th weeks- partitioning of cloaca into anterior
urogenital sinus and posterior anorectal canal by midline
fusion of 2 lateral ridges of cloacal wall and by descending
urorectal septum. (some believe this septum formation and
fusion of cloacal membrane never occur).
• 24th day- nephric (wolffian) duct fuses with cloaca– Cephalad vesicourethral canal- bladder and pelvic
urethra.
– Caudal urogenital sinus- phallic urethra for males,
distal vaginal vestibule for females.
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• Primitive trigone- day 33- right and left
common excretory ducts (mesonephric) fuse
midline as this triangular area.
• Smooth muscle develops from the bladder dome
and extends to base and urethra.
• Bladder body- endoderm and surrounding
mesenchyme, trigone- mesoderm.
• Week 12- urachus involutes into median
umbilical fold.
• Week 21- bladder epithelium 5 cell layers thick.
Ureter
• Complete lumen at 28 days- transient luminal
obstruction at 37-40 days and recanalizes starting
at the midureter.
• 37-39 days- Chwalla’s membrane- 2 cell thick
layer over ureteric orifice.
• 12 weeks- smooth muscle and elastic fibers
(smooth muscle begins at UVJ and ascends)occurs later than bladder.
• 14 weeks- transitional epithelium- occurs by
epithelial-mesenchymal interaction.
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Renin-Angiotensin System
• Responsible for fetal glomerular filtration,
urine production, growth/development of
kidney and ureter (mothers treated with
ACE-inh- oligohydramnios, hypotension,
anuria).
Genital Development
• Genital ridge mesenchyme- primitive sex cordsafter 6 wks develop different fates in male/female
(paramesonephric/mullerian ducts also form):
– SRY (sex-determining region of Y chromosome)differentiate into Sertoli cells, 7th week- testis
cords/rete testes, puberty- seminiferous tubules.
• Sertoli cells secrete MIS (mullerian-inhibiting substance)regression of mullerian ducts at weeks 8-10 (remnants=
appendix testis, prostatic utricle).
• Week 9-10- Leydig cells form testosterone.
– Stimulates wolffian ducts to form vas (8-12 weeks).
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– Absent SRY- differentiate into ovarian
follicles.
• Primitive sex cords degenerate and secondary sex
cords form- forms ovarian follicles.
– Germ cells become oogonia and enter first meiotic
division as primary oocytes (puberty- oocytes resume
gametogenesis due to monthly gonadotropin surges).
– Wolffian ducts degenerate.
– No MIS in females so no regression of mullerian ductsmullerian ducts form fallopian tubes, uterus, and upper
2/3 vagina.
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Prostate/Seminal Vesicle
• Prostate/bulbourethral glands- from
urethra/urogenital sinus (10-12 weeks)- at
puberty testosterone rises and prostate size
increases.
• Seminal Vesicle- (10th week) sprout from
distal mesonephric ducts in response to
testosterone.
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External Genitalia
• Mesodermal cells form rudiments of external genitalia.
• They spread around cloacal membrane to form swellings.
• 5th week- cloacal folds develop on either side of cloacal membranemeet anteriorly to form midline swelling called genital tubercle.
• Cloacal folds differentiate into urogenital folds and anal folds.
• Labioscrotal folds form on each side of urogenital folds.
• Urethral groove and urethral plate fuse to form penile urethra.
• Females- no androgen receptor signaling by DHT- perineum doesn’t
lengthen and labioscrotal and urethral folds do not fuse at midline.
– Phallus bends inferiorly- becomes clitoris.
– Urethral folds- labia minora.
– Labioscrotal folds- labia majora.
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Gonadal Descent
• Testicles/ovaries lie near kidney before gonadal differentiation- held
there by 2 loose ligaments– Ventral- gubernaculum.
– Dorsal- cranial suspensory ligament (CSL).
• Males (week 10-15)- at inguinal region- gubernaculum enlarges, CSL
regresses.
– Inguinoscrotal migration (7th month)- gubernaculum descends to
scrotal location and is hollowed out by peritoneal diverticulum
(processus vaginalis).
• Females- ovary moves cranially- CSL develops, gubernaculum
involutes.
– Ovaries suspended in broad ligaments of uterus. (3rd month).
– “Female gubernaculum” becomes round ligament.
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References
• Campbell-Walsh Urology- Ninth Edition
(2007), Vol. 4, Chapter106- Normal
Development of the Urogenital System.
• Langman’s Medical Embryology- Ninth
Edition (2000), Chapter14- Urogenital
System.