Urogenital embryology Flashcards
What layer of mesoderm do the urogenital system develop from?
Intermediate mesoderm
Note this is the internal genital system
What is one of the key transcription factors making the intermediate mesoderm?
Pax2
What are the three stages of kidney formation?
Pronephros
Mesonephros
Metanephros
What are the key features of pronephros?
Develop in the anterior embryo -> early kidney buds form early 4w gestation
Grows causally into the nephrogenic cord to give way to the mesonephros
Degenerates into adulthood
What are the key features of the mesonephros?
Nephrogenic cord extend and anterior buds degenerate
Forms a long chain of kidney buds
Will either degenerate by term or becomes the ductus deferens
What are the key features of the metanephros?
Develops in Posterior embryo as final part of the nephrogenic cord -> becomes adult human kidney
Consists of two cell populations -> ureteric bud and metanephrogenic mesenchym
What emrbyological structure contribute to the mature kidney in adults?
Metanephros
What causes the development of the metanephros into the ureteruc bud?
Due to signalling of the surrounding metanephrogenic mesenchyme
GDNF signalling from mesenchyme causes outgrowth of the ureteric bud by binding to RET receptors
How does GDNF signalling affect the urteric buds?
Activates Wnt signalling back into the mesenchyme - specific Wnt9b
Promotes mesenchymal-epithelial transition - mesenchyme develops into epithelial tubules of the kidney.
What are the stages of development of the metanephrogenic mesenchyme into the renal tubules?
Cap mesenchyme around the uretric bud tip developes into renal vesicles, which become comma then S shaped
S shpaed eventually develop into the nephron which the ureteric stalk becoming the collecting duct
How does the glomerulus develop in the nephron?
Differentiated mesenchyme into renal epithelial cells in the capsule secretes VEGF which attracted vascular progenitor cells.
What is the complex morphogenesis of the cloaca?
The metanephric duct grows donwards into the urogenital sinus.
In females the duct then degnerates
In males forms the ducts deferens
The cloaca then separates and the bladder grows - urorectal septum separates the urogenital sinus from the hindgut.
What is the kideny ‘ascent’ in emnryogenesis?
The embryo grows around the kidneys and the ureter lengths during the first trimester.
This causes the kidneys to become laterally displaced, rotated and relatively ascend.
What are some examples of congenital malpositioning of the kidneys?
Of rotation - anterior or lateral hilum
Renal fusion - too close during ascent and merge
Ectopia - wrong position or wrong side
What are the concerns of hypoplasia of the kidenys?
Hypoplasia - concerning when bilateral - mutations in PAX2 and Eya1 (regulates GDNF)
What are the key features of agenesis of the kidneys?
Lethal in neonates due to lung problems
Reduces amniotic fluid (oligohydramnios)
Potter sequence - flat fate, limb contractures, low-set eears, wrinkled skin, lung hypoplasia
What are primordial germ cells?
Form germ line - give rise to gametes of the organism (DNA inherited by next generation)
How do primordial germ cells enter the mesoderm?
Found in the posterior end of embryo
Migrate through gut wall/mesentery and into the genital ridges of the intermediate mesoderm.
What structure do the gonads develop from?
The intermediate mesoderm
What duct is important for the development of the female genital system?
The paramesonephric duct
This will degnerate in males
What develops from the urogenital ridge?
Splits into the medial genital ridge -> becomes the gonads
And laterally the nephrogenic ridge -> becomes the kidneys, ureters and bladders
How does the genital ridge know to become male or female?
Expression of transcription factors:
Sry/Sox9 protein and Wt1/Wnt
What is the role of transcription factors in the development of the male genitalia from the genital ridge?
Y chromosome -> Sry gene -> protein acts as transcription factor
Causes expression of Sox9
Sox9 increases expression of Fgf9 alongside other testes forming genes such as AMH
Leads to testes
Sox 9 -> Inhibits B-catenin
Fgf9 -> inhibits Foxl2
Suppresses ovary development
What is the role of transcription factors in the development of the ovaries?
XX chromosome - no Sry gene so no Sox9 expression
Wnt4 expression leads to B-catenin expression (further suppresses Sox9)
Triggers expression of Foxl2 (further suppresses Fgf9) leads to ovary development and suppressed testis development
When do the gonads develop in the embryological timeline?
Rudimentary at week 4
PGC migrate in at week 6
Sexual differentiate at week 7
What is the key process of PGCs affect in female development?
Develop into eggs
Arrest in meiosis (finite number as no stem cell population remain)
Surrounding granulosa cells and thecal cells are stimulated by paracrine signalling from PGCs to secrete estrogens
What is the key process by which PGCs affect development of the male reproductive system in embryology?
PGCs arrest in week 6 of development
Arrest in mitosis - stem cell population still exist - males have a finite population of sperm
Paracrine signalling causes sertoli cells to secrete AMH and Leydig cells to secrete testosterone
What embryological ducts degenerate in what gender?
Wolfian duct (mesonephric duct) degenerates in females
Mullerian duct (paramesonephric duct) degenerates in males
What genital feature morphogenesis is hormone dependent?
Females - uterus, cervix and vagine
Males - prostate, bulborurethra, seminal vesicle and testes
What regulates the development of the genital ducts into their mature structures?
Hox genes expression
How does the external genitalia develop?
The genital ridge will have an outgrowth the genital tubercle which becomes the phallus
After development of the gonads and hormones production starts (7w gestation)
This will develop into the glans (penis) or the clitoris)
What is the role of genital swelling in the emrbyological development of the genitals?
Hormone dependent
Becomes the scrotum or the labia majoris
