Genitourinary Development, Embryology and Defects
Male system-one part of the preserved urinary system
- Functionally, mesonephros functions for only a short period of time-contributes to amniotic fluid by minimal urine contribution
- Metanephric-provision of dilute urine to the amniotic fluid-this fluid is very important for proper development
Pronephros/Pronephric Kidney
- starts developing by 21 days and already begins to degenerate by 28
- begins a few cervical mesotomes, or nephrotomes
- PRONEPHRIC KIDNEY DOES NOT PRODUCE URINE
- Growth is CRANIAL à CAUDAL-from pronephros to eventual development of the metanephric kidney
- Pronephros-not so important for the development of the fetus, but does give rise to a duct that eventually enters the cloaca-this is the mesonephric duct-and this structure is conserved for the male reproductive system
PRONEPHRIC DUCT GIVES RISE TO THE MESONEPHRIC DUCT
CLINICAL CORRELATION: When you find portions of the mesonephric duct missing, there can be fertility problems
Mesonephros-has a development similar to the metanephric but its much simpler
Ø Mesonephric duct does not enter into the function of the metanephric kidneys
Ø Development of kidney and genital system is from a mass of intermediate mesoderm-nephrogenic cord
Ø Nephrogenic Cord-develops the urogenital ridges from which from which kidneys, urinary system, and the male genital system develop
nephrogenic cord -> UG ridges -> kidneys and urinary system -> male genitalia
Ø Formation of mesonephric duct begins w/ formation of pronephric duct and the formation of hollow balls of cells that elongate, giving rise to the mesonephric duct-at the distal end of this duct is where you eventually see the formation of the metanephric kidney
Ø As the pronephric kidney begins to degenerate-about day 28-you begin to see the formation of what appears to be the renal corpuscle-this is all simple-and this is all occurring cranial to caudal
Ø As pronephric kidney degenerates, mesonephric kidney develops
Adult Kidney
- During development, you can check normal development by amount of amniotic fluid
- Much of amniotic fluid comes from the urine produced by the metanephric kidney
Oligohydramnios-scanty amniotic fluid
- Worst thing you can see is bilateral atresia of the metanephric kidneys-seen b/c not enough urine is produced
- Potter’s Syndrome-a physical compression of the developing baby because of oligohydramnios-there’s many deleterious processess going on during development-not enough amniotic fluid means no medium to grow in-baby as dry skin and a beak-shaped head
- Cytsic disease
Polyhydramnios-normally, baby continuously swallows amniotic fluid, so if the esophagus is not working correctly, then you get a buildup of amniotic fluid
Metanephric Kidney-origin in two places w/ two structures working via mutual inducement
1) URETERIC BUD-outgrowth of the mesonephric duct in the general area where the duct enters into the cloaca-bud grows out to the metanephric blastema-when you think ureteric bud, you must think collecting tubule
2) METANEPHRIC BLASTEMA-develop into the nephrons-think metanephric blastema, think renal corpuscle
- If either the bud, or the blastema, does not form and function correctly, then kidney does not function
- Ureteric bud divides-this is the area of the pelvis-and start to form the major and minor calyx
- Calices divide, develop, then regress and coalesce into the minor calices-and then you start to get the small collecting ducts formed
Metanephric blastema-eventually forms a vesicle and under induction by the ureteric bud, you get the development of the METANEPHRIC TUBULE which eventually gives rise to the NEPHRON-further along, there’s branching of this tissue and you start to see the formation of a Bowman’s capsule
COLLECTING TUBULE-derivation of the ureteric bud
- Glomerulus & Bowman’s capsule, proximal convoluted tubule, Henle’s Loop, macula densa, and distal convoluted tubule = renal corpuscle-derived from the Metanephric blastema
- After the nephrons become developed-there is continued hypertrophy of the nephrons
Ureteric Bud -> hits metanephric blastema -> forms vesicle & metanephric tubule -> nephron -> Bowman’s
Bladder and Urethra-development from the cloaca
Urogenital Sinus-three major portions
1) Cranial-Vesicular portion-gives rise to the portion of urethra proximal to entry of ejaculatory ducts
2) Pelvic portion-distal portion of the prostatic urethra and membranous urethra
3) Phallic portion-gives rise to the spongy urethra
- Development of the bladder in the male and female is similar; it’s development of urethra that differs
- Ureter is developed from the ureteric bud-this grows into the UROGENITAL SINUS
- Bladder is formed from the vesicular portion of the urogential sinus & it becomes complicated in male urethra formation
- Female-all the epithelium of the urethra comes from the vesicle portion of urogenital sinus
- Male-there’s contributions from four separate sources of epithelium
Ø ejaculatory duct is the joining of the vas deferens and the seminal vesicles
n Portion of Urethra not from urogenital sinus-Navicular Fossa
Male Urethra-Four sources
1) Vesicular portion of UG sinus-gives rise to the prostatic urethra proximal to ejaculatory duct
2) Pelvic portion of UG sinus-gives rise to the distal prostatic and membranous urethra
3) Phallic portion of UG sinus-gives rise to the spongy urethra
4) Glandular plate-ectodermal structure that gives rise to navicular fossa
Ø half of the prostatic urethra comes from vesicular; distal half comes from pelvic
Ascent of the Kidney
- Kidney ascend b/c the caudal portion of the embryo begins to grow quickly-it grows “away” from the kidney
- Blood flow will “attach” and “detach” from the kidney
- In final position, they feed off of the renal artery
- During the ascent, the kidney’s rotate
- Both kidneys need to move up at the same time-or else Malrotation
Genitourinary Abnormalities
- Incorrect function of the ureteric bud, thus there could be only one functional kidney
- Development of bifid ureter-ureter will function normally but this creates a place for kidney stones to settle-the ureters formed have smaller diameter-hence, less space for the kidney stone to fall through
- Incorrect ascension-you can get a “horseshoe” shaped kidney
- There can be a supernumery kidney where an extra kidney is formed
Pre-12 week, based on the external genitalia, there’s an indifferent stage
6th week-prim. germ cells migrate & end up in the genital ridge-as soon as this migration occurs, there’s subsequent development of genitalia
- If no testis develops, a female occurs-no estrogens required for a female to be developed in utero
- Male-testis secrete androgens
- Female-ovaries don’t secrete estrogens until menarche
- On Y-chromosome is SRY region-responsible for development of the testis
MALE-there’s cascade of events from primitive gonad to full grown male
- Sertoli cells produce Mullerian(Paramesonephric) Duct Inhibitory Factor, or MIF
- MIF causes regression of the Mullerian duct
- Internal genital ducts are both present in both sexes
Leydig Cells-produce testosterone
- Testosterone causes mesonephric duct to differentiate into the epididymis, vas deferens, & seminal vesicles
- Testosterone can be converted via 5--reductase to form dihydrotestosterone-development of penis and scrotum
- All sorts of problems can arise with this complex cascade
- Problem in the formation of dihydrotesterone = no penis and no scrotum and no sex
MALE-primitive germ cells develop in MEDULLARY AREA of developing gonad
- Mullerian becomes atretic
MALE-develop seminiferous tubules, the rete testis, and then vas deferens and duct system
- vas deferens, epididymis, seminal vesicle, and efferent ducts are derivations of the Wolffian ducts under influence of androgen
ANDROGEN stimulates Wolffian Ducts -> vas, epididymis, seminal vesicles, efferent ducts
- adult-no semen in ejaculation-you may find underdeveloped vas deferens-and hence, no transport
- seminal vesicle provides the fructose of semen
Medullary Sex Cords form the seminiferous tubules and rete testis
Vas deferens-where it enters into the urethra is the ejaculatory duct-this is where Dr. B looks for the presence of fructose-if no fructose, then you know there’s problem with this duct
- Secretions in absence of the Vas Deferens are purely prostatic and bulbourethral(Cowper’s) secretions
FEMALE- primitive germ cells develop in the CORTICAL REGION
- Wolffian duct atretic
- Mullerian duct will come into contact with the urogental sinus-this is the sinus tubercle
- Mullerian duct move inwards, zip together, forming the uterus, 80% of vagina, and fallopian tube
- This would happen to every fetus, if there was not the presence of androgen
- 80% of vagina = Mullerian duct; 20% of vagina = urogenital sinus
Abnormalities w/ paramesonephric(Mullerian) duct
- “zipping” complex can be incomplete
- small septum retained in vagina
- Two separate horns of the uterus-no zipping occurred
- Many of these abnormalities can be surgically corrected
- Internal duct system-exposure to androgens forms male
There’s development of phallus and tubercle found in both male and female-these are indistinguishable for a time
- secretion of androgen causes the phallus to give rise to penis
- labioscrotal swelling-scrotum
- urogenital groove closes to form shaft of penis
- canalization completes the joining to form the urethra
MALE = MEDULLARY CORD
FEMALE = CORTICAL REGION
Female
- Absence of androgen-phallus develops into clitoris
- Urogenital groove does not close
- Labioscrotal swelling gives rise to the labium minora and majora
Male Abnormalities-some due to androgens not present at the right time
- external opening of urethra on the ventral side of the penis
- canalization may not be complete
- Scrotal hypostadius-urethra comes out of the testis
- Epistadius-failure of canalization on the dorsal side of penis
- Two peni-fissure of the developing phallus-two fully functional penis
- For normal sperm development, you must have descent of the testis for proper temperature of sperm growth
- Descent of testis through the inguinal canal
- There’s an attachment of the testis to the gubernaculum which is attached to the labioscrotal folds on either side
- As it is acted on by androgens, the gubernaculum pulls the testis down
- In female, there’s attachment of ovaries to the gubernaculum but because there’s no androgen secreted, there’s is no pulling down of the ovaries
INTERSEXUALITY-mostly genetically based
True Hermaphrodites-presence of both ovaries and testis
- there can be an ovary on one side and a testis on the other
- most true hermaphrodites are raised as males-most don’t show the problems until the time of puberty
Lateral Hermaphrodite- person with male external genitalia and some female genitalia-like breasts and a penis
- presence of androgens
Pseudo-Hermaphrodites-could be due to having non-functional androgen receptors
- males have the correct genetic statement-46XY
- abdominal testis-no sperm formed and highly cancerous
- If there’s a problem is the cortisol pathway, there can be exposure of the developing female to androgens, in which case you get masculinization of the female genitalia
Congenital Andrenal Hyperplasia-genitic female with facial hair, short stature
- too much androgen produced
- genetically 46XX but too much androgen produced because of a defect in the cortisol pathway
- can help cure by giving small amounts of estrogen
Klinefelter’s Syndrome-1/500
- mean span of arms is greater than the height
- some breast development
- very small testis b/c low amount of testosterone
- most of the germinal elements of the testis have been replaced by hyaline-so you can test the individual by squeezing the testis and getting no aching feeling-Ouch
- 47XXY
Turner’s Syndrome-1/5000
- no ovaries
- connective tissue where the ovaries should be-”streak ovaries”
- there’s a pre-pubital uterus and vagina
- Hands are held outward
- webbing from the neck
- no estrogen produced
- can help by giving her estrogen-but you have t o continue giving her estrogens for the rest of her life
- the doctor has to be her ovaries
- many Turner’s Syndrome females have carried a baby to term
- Through IVF, you can get it all such that these people can become mommies
Urogenital System Anomalies
Review: Mesonephric/Wolffian duct gives off ureteric duct à induces metanephric blastema to form kidney
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Metanephric duct incorporated into urogenital sinus-subsequently, trigone formed
UNILATERAL RENAL AGENESIS-means you have one functioning kidney
BILATERAL RENAL AGENESIS-no kidneys-problem w/ mesonephric duct and ureteral duct
- Renal Agenesis is often thought to be related to the fact that no ureteral bud forms off of the mesonephric duct
- problem w/ the duct means no normal ureteric bud forms, means no kidney forms
- Kidney formation is via an induction event where the ureteric bud is the inducer-so to speak
TQ-NO KIDNEY DOES NOT MEAN NO ADRENAL GLAND-the two are not embryologically related
Ø No mesonephric duct, then NO ureter, NO vas deferens, NO seminal vesicles, NO renal artery, and an under-developed bladder-a hemi-trigone
Ø BILATERAL RENAL AGENESIS IS INCOMPATIBLE WITH LIFE
- Children die of hypoplastic lungs and have Potter’s faces
- Ear and renal anomalies tend to go together………don’t ask
ANOMALIES IN POSTION-related to the medial rotation of kidney as it ascends
Review again-ureteric bud hits metanephric blastema, kidney is in pelvis, then ascends, taking blood supply from arteries along their course, and then the kidneys rotate medially
- Most kidneys are normal in function; they are just funny looking…….yeah, it’s hilarious alright
Pelvic Kidney-kidney un-ascended-lies in pelvis…only real problem could be with the w/ collecting system
Intra-thoracic kidney-uncommon-usually occurs on the left side
Crossed(fused) Renal Ectopy-a fusion anomaly-usually occurs on right-kidneys stick together and goto right side
- w/ crossed ectopia, the ureters still enter bladder in normal position b/c it was the ureteric bud coming off mesonephric duct that induced this part of the kidney-everything’s normal until they start ascent
HORSESHOE KIDNEY-most common fusion anomaly
- usually fuse at lower pole and the kidneys’ ascent is often cut short-the isthmus of the kidney hits the IMA
HORSESHOE KIDNEY ASCENT IS CUT SHORT BY IMA
- Normal induction of renal arteries is all funked up
Horseshoe Kids are the most common fusion anomaly and are most likely to have obstructions, or to have problems
Normally-Wolffian duct is incorporated distally, w/ ureter above, and the duct gives rise to vas and seminal vesicles
URETERAL DUPLICLATION-two ureteral buds coming off the duct instead of one-you get complete duplication
- the ureter going to the upper pole of kidney inserts into the urogenital sinus more distal than the ureter than drains the lower pole
ALWAYS: ureter from upper pole drains into bladder(urogenital sinus) more distal than the ureter of lower pole
- w/ complete ureteral duplication, vas, seminal vesicle are in normal position
- ureters draining upper pole, going to distal bladder, get lost-they can get into the urethra-ectopic ureters
- ureters that drain lower pole have high chance for urine reflux-b/c of underdeveloped submucosal tunnels
- urine reflux-always w/ lower pole ureter b/c its the one going up and out
- Again, the ureter near the bladder neck drains the upper pole and the ureter more lateral on bladder drains lower pole
Incomplete Duplication-ureteral bud splits before hitting the mesonephric duct
Ectopic Ureter-usually occurs w/ duplication and the ureter from upper pole, draining distally, gets lost
- the ureter can enter ectopically into the seminal vesicle
- Chief complaint of little girl, “Always wet”-suspect ectopic ureter due to upper pole ureter ectopic in introitus
Retrocaval Ureter-ureter comes from rt. kidney, goes behind IVC, b/t IVC and aorta, then swings out-ureteral obstruction
Retrocaval Ureters occur because of PERSISTENCE OF THE VENTRAL SUBCARDINAL VEIN
Normally: bladder forms from urogenital sinus-the urorectal folds go down, and the bladder forms anterior; the cloacal membrane is on the bladder but gets reabsorbed and there’s mesodermal ingrowth from sides to cover up the bladder
Bladder Extrophy-mesodermal ingrowth from sides in inhibited b/c of PERSISTENT CLOACAL MEMBRANE
- presents w/ bladder, penis, and prostate exposed
Urachus-fibrous cord derived from allantois, connected to urogenital sinus along w/ elongation of umbilical cord
Normally: urachus ascends from bladder to umbilicus, then turns into cord
Prune Belly-abdominal muscle deficiency w/ dilated urinary tract and undescended testicles-also called triad syndrome
Patent Urachus-can have urine coming out of umbilicus, or a urachal cyst which makes you worry of cancer
Tags: bladder extrophy, bowman's capsule, ectopic ureter, glomerulus, Henle's loop, lateral hermaphrodite, leydig cells, macula densa, male genitalia, mesonephric duct, metanephric blastema, metanephric kidney, mullarian duct, navicular fossa, nephrogenic cord, oligohydramnios, patent urachus, potter's syndrome, pronephric duct, pronephric kidney, pronephros, prune belly, retrocaval ureter, sinus tubercule, uritogenital ridges, urogenital sinus, uteric bud, vas deferens
