Development*of*the*Urogenital*system*I*
• Urogenital+system+is+predominantly+derived+from+the+intermediate+
mesoderm+
• Intermediate+mesoderm+!+Mesonephros+(intermediate+excretory+organ+–+
helps+the+baby+while+it+is+in+an+aqueous+environment)+!+metanephros+
(mature+kidney,+as+it+forms,+the+mesonephros+disintegrates)+
• Pronephros+is+a+modified+structure+that+helps+with+this+transition+but+it’s+
role+is+controversial+(some+people+say+it’s+not+needed+in+mammals)+
• Mesonephros+is+made+up+of+the+mesonephric+duct+(aka+wolfian/+nephric).+
This+duct+integrates+the+mesoderm+and+endoderm+by+entering+the+cloaca+
(the+caudal+end+of+the+gut,+made+up+of+endoderm+and+gives+rise+to+the+anal+
canal).+
• The+nephric+duct+integrates+into+the+cloaca,+whereas+the+cloaca+gets+split+
into+two+(because+of+the+action+of+a+urorectal+septum,+this+causes+the+
ventral+aspect+to+be+the+urogenital+sinus,+and+the+dorsal+aspect+is+the+anal+
canal)+
• The+mesonephric+duct+drains+into+the+urogenital+sinus+(which+will+later+
become+the+bladder)+
• The+metanephric+rudiment+forms+–+this+is+composed+of+the+metanphric+
blastema+(intermediate+mesoderm)+and+urteric+bud.+This+development+
starts+at+week+10+and+continues+until+week+30.+This+means+premature+
babies+(before+week+30)+are+likely+to+develop+nephrotic+syndrome+later+
on+in+life.++
• Metanephric+blastema+gives+rise+to:+
o Epithelia+of+nephrons++
o Stroma,++
o Endothelia+
• Urteric+bud+is+the+most+important,+if+there+is+no+urteric+bud+there+is+no+
kidney.+Gives+rise+to+:+
o Collecting+tubule+epithelia++
o Epithelia+of+renal+pelvis,+minor+and+major+calyx,+and+ureter.++
• As+the+kidneys+grow,+they+ascend+from+the+pelvis+to+their+proper+
placement+in+the+abdomen.+Because+new+vascular+connections+to+the+
aorta+are+made+at+the+same+time,+sometimes+the+blood+vessels+may+block+
this+ascension+of+the+kidneys+and+cause+abnormalities.++
• When+one+kidney+hasn’t+ascended,+this+is+called+the+pelvic+kidney.+When+
both+don’t+ascend+and+fuse,+it+is+called+the+horseshoe+kidney.++
• Although+this+is+caused+by+abnormal+vasculature,+there+is+some+evidence+
that+it+is+genetic+as+well.+FoxdS1+deletion+causes+pelvic+and+horseshoe+
kidney.+
• Abnormal+vasculature+/+aberrant+vessels+also+cause+obstructions+in+the+
pathway+of+the+urine+through+the+ureter+and+renal+pelvis,+this+condition+is+
called+hydronephrosis.+This+causes+enlargement+of+the+renal+pelvis+and+
can+happen+in+two+places+most+frequently:+
o The+ureteropelvic+junction+"+most+common+urinary+tract+
obstruction,+poorly+understood,+can+be+diagnosed+by+the+
enlargement+of+ONLY+the+pelvis.+
, o The+ureterovesical+"+less+common,+between+the+ureter+and+the+
bladder,+both+the+pelvis+and+the+ureter+are+enlarged.++
• The+junction+of+the+ureterS+cloaca+has+to+be+remodeled+to+make+the+
bladder:+
o This+occurs+through+incorporation+of+the+ureters+(from+the+ureteric+
bud)+integrating+into+the+urogenital+sinus+(the+bladder)+and+fusing+
at+week+6.++
o Apoptosis+is+also+involved+in+this+process+as+both+the+wolffian+duct+
and+the+ureter+integrate+collectively+into+the+urogenital+sinus,+but+
separation+needs+to+occur.++
• Signalling+between+the+metanephric+blastema+,+nephric+duct,+and+the+
urteric+bud+is+essential+for+the+development+of+the+kidney.++
• Metanephric+blastema+secrets+factors+that+mediate+the+outgrowth+of+
ureteric+bud+from+the+nephric+duct,+as+well+as+continued+branching.+These+
factors+are+reliant+on+CSret+and+FGF+receptors.++
• WNT+genes+(specifically+Wnt+9b)+were+found+to+be+sufficient+for+signaling+
in+absence+of+uteric+bud.++
• The+ureteric+bud+induces+the+metanephric+blastema+to+go+from+
mesenchyme+to+epithelium.+Two+genes+are+required+for+this+transition+"+
The+wilms+tumor+gene+WTS1+(when+abberant,+causes+tumors+in+the+
kidney)+as+well+as+the+PaxS2+transcription+factors+(when+abberant+causes+
both+kidney+and+eye+problems)+
• When+epithelium+is+established,+the+embryonic+podocytes+of+the+kidney+
secrete+factors+VEGF+to+create+the+glomerular+capillary+network.++
• Negative+signaling+and+inhibition+is+needed+to+make+sure+not+more+than+
one+ureter+is+present.++
• Early+embryo+is+sexually+indifferent.+There+are+three+tissues+that+need+to+
be+formed+to+form+the+sexual+organs:+
o Gonadal+ridge+!+forms+gonads+
o Germ+cells+(yolk+sac)+!+migrate+into+the+gonads+and+form+gametes+
o Two+ducts:+
# Mesonephric+/+wolfian+duct+
# Paramesonephric+/+mullerian+duct.++
• The+germ+cells+migrate+along+the+dorsal+mesentry+into+the+gonads+at+the+
5th+/+6th+week+of+development.+This+is+because+their+differentiation+is+
reliant+on+the+environment+in+the+gonads+"+abnormal+migration+=+not+a+
suitable+differentiation+environment+=+teratomas.+
• Paramesonphreic+ducts+are+made+from+an+invagination+in+the+coelomic+
epithelium.+This+gives+rise+to+a+duct+that+is+ADJACENT+to+the+mesonephric+
duct.+At+this+point,+there+are+two+ducts+and+the+embryo+is+sexually+
indifferent.++
• When+there+is+a+functional+Y+chromosome,+by+the+4th+month:+
o Mullerian+duct+disintegrates+
o Nephric+duct+becomes+the+vas+deferens.+++
o Determination+occurs+due+to+the+SRY+(sex+determining+region+of+
the+Y+chromosome)+which+gives+rise+to+the+testis.+
o The+testis+then+develop+3+cells:+
# Leydig+cells+(secrete+testosterone,+causes+the+persistence+of+
wolfian+duct+as+well+as+the+production+of+sperm)+
• Urogenital+system+is+predominantly+derived+from+the+intermediate+
mesoderm+
• Intermediate+mesoderm+!+Mesonephros+(intermediate+excretory+organ+–+
helps+the+baby+while+it+is+in+an+aqueous+environment)+!+metanephros+
(mature+kidney,+as+it+forms,+the+mesonephros+disintegrates)+
• Pronephros+is+a+modified+structure+that+helps+with+this+transition+but+it’s+
role+is+controversial+(some+people+say+it’s+not+needed+in+mammals)+
• Mesonephros+is+made+up+of+the+mesonephric+duct+(aka+wolfian/+nephric).+
This+duct+integrates+the+mesoderm+and+endoderm+by+entering+the+cloaca+
(the+caudal+end+of+the+gut,+made+up+of+endoderm+and+gives+rise+to+the+anal+
canal).+
• The+nephric+duct+integrates+into+the+cloaca,+whereas+the+cloaca+gets+split+
into+two+(because+of+the+action+of+a+urorectal+septum,+this+causes+the+
ventral+aspect+to+be+the+urogenital+sinus,+and+the+dorsal+aspect+is+the+anal+
canal)+
• The+mesonephric+duct+drains+into+the+urogenital+sinus+(which+will+later+
become+the+bladder)+
• The+metanephric+rudiment+forms+–+this+is+composed+of+the+metanphric+
blastema+(intermediate+mesoderm)+and+urteric+bud.+This+development+
starts+at+week+10+and+continues+until+week+30.+This+means+premature+
babies+(before+week+30)+are+likely+to+develop+nephrotic+syndrome+later+
on+in+life.++
• Metanephric+blastema+gives+rise+to:+
o Epithelia+of+nephrons++
o Stroma,++
o Endothelia+
• Urteric+bud+is+the+most+important,+if+there+is+no+urteric+bud+there+is+no+
kidney.+Gives+rise+to+:+
o Collecting+tubule+epithelia++
o Epithelia+of+renal+pelvis,+minor+and+major+calyx,+and+ureter.++
• As+the+kidneys+grow,+they+ascend+from+the+pelvis+to+their+proper+
placement+in+the+abdomen.+Because+new+vascular+connections+to+the+
aorta+are+made+at+the+same+time,+sometimes+the+blood+vessels+may+block+
this+ascension+of+the+kidneys+and+cause+abnormalities.++
• When+one+kidney+hasn’t+ascended,+this+is+called+the+pelvic+kidney.+When+
both+don’t+ascend+and+fuse,+it+is+called+the+horseshoe+kidney.++
• Although+this+is+caused+by+abnormal+vasculature,+there+is+some+evidence+
that+it+is+genetic+as+well.+FoxdS1+deletion+causes+pelvic+and+horseshoe+
kidney.+
• Abnormal+vasculature+/+aberrant+vessels+also+cause+obstructions+in+the+
pathway+of+the+urine+through+the+ureter+and+renal+pelvis,+this+condition+is+
called+hydronephrosis.+This+causes+enlargement+of+the+renal+pelvis+and+
can+happen+in+two+places+most+frequently:+
o The+ureteropelvic+junction+"+most+common+urinary+tract+
obstruction,+poorly+understood,+can+be+diagnosed+by+the+
enlargement+of+ONLY+the+pelvis.+
, o The+ureterovesical+"+less+common,+between+the+ureter+and+the+
bladder,+both+the+pelvis+and+the+ureter+are+enlarged.++
• The+junction+of+the+ureterS+cloaca+has+to+be+remodeled+to+make+the+
bladder:+
o This+occurs+through+incorporation+of+the+ureters+(from+the+ureteric+
bud)+integrating+into+the+urogenital+sinus+(the+bladder)+and+fusing+
at+week+6.++
o Apoptosis+is+also+involved+in+this+process+as+both+the+wolffian+duct+
and+the+ureter+integrate+collectively+into+the+urogenital+sinus,+but+
separation+needs+to+occur.++
• Signalling+between+the+metanephric+blastema+,+nephric+duct,+and+the+
urteric+bud+is+essential+for+the+development+of+the+kidney.++
• Metanephric+blastema+secrets+factors+that+mediate+the+outgrowth+of+
ureteric+bud+from+the+nephric+duct,+as+well+as+continued+branching.+These+
factors+are+reliant+on+CSret+and+FGF+receptors.++
• WNT+genes+(specifically+Wnt+9b)+were+found+to+be+sufficient+for+signaling+
in+absence+of+uteric+bud.++
• The+ureteric+bud+induces+the+metanephric+blastema+to+go+from+
mesenchyme+to+epithelium.+Two+genes+are+required+for+this+transition+"+
The+wilms+tumor+gene+WTS1+(when+abberant,+causes+tumors+in+the+
kidney)+as+well+as+the+PaxS2+transcription+factors+(when+abberant+causes+
both+kidney+and+eye+problems)+
• When+epithelium+is+established,+the+embryonic+podocytes+of+the+kidney+
secrete+factors+VEGF+to+create+the+glomerular+capillary+network.++
• Negative+signaling+and+inhibition+is+needed+to+make+sure+not+more+than+
one+ureter+is+present.++
• Early+embryo+is+sexually+indifferent.+There+are+three+tissues+that+need+to+
be+formed+to+form+the+sexual+organs:+
o Gonadal+ridge+!+forms+gonads+
o Germ+cells+(yolk+sac)+!+migrate+into+the+gonads+and+form+gametes+
o Two+ducts:+
# Mesonephric+/+wolfian+duct+
# Paramesonephric+/+mullerian+duct.++
• The+germ+cells+migrate+along+the+dorsal+mesentry+into+the+gonads+at+the+
5th+/+6th+week+of+development.+This+is+because+their+differentiation+is+
reliant+on+the+environment+in+the+gonads+"+abnormal+migration+=+not+a+
suitable+differentiation+environment+=+teratomas.+
• Paramesonphreic+ducts+are+made+from+an+invagination+in+the+coelomic+
epithelium.+This+gives+rise+to+a+duct+that+is+ADJACENT+to+the+mesonephric+
duct.+At+this+point,+there+are+two+ducts+and+the+embryo+is+sexually+
indifferent.++
• When+there+is+a+functional+Y+chromosome,+by+the+4th+month:+
o Mullerian+duct+disintegrates+
o Nephric+duct+becomes+the+vas+deferens.+++
o Determination+occurs+due+to+the+SRY+(sex+determining+region+of+
the+Y+chromosome)+which+gives+rise+to+the+testis.+
o The+testis+then+develop+3+cells:+
# Leydig+cells+(secrete+testosterone,+causes+the+persistence+of+
wolfian+duct+as+well+as+the+production+of+sperm)+
