Postnatal restoration of the mouse urinary bladder urothelium

Mouse urothelium is disrupted just before birth, followed by a postnatal re storation process which includes cell proliferation, death and differentiat ion. We assessed urothelial proliferation by the expression of proliferatin g cell nuclear antigen (PCNA), desquamation by electron microscopy, and apo ptosis by TUNEL staining and urothelial differentiation by the expression o f uroplakins and cytokeratin 20 (CK20) as well as the apical plasma membran e maturation. Our results indicated that urothelial proliferation was high from birth until about the 14th postnatal day. A majority of basal cells an d even occasional superficial cells were PCNA positive during the first 5 p ostnatal days. Cell death occurred during the first 9 postnatal days. Betwe en birth and day 5, single cells underwent apoptosis, whereas between days 6 and 9 cells mainly desquamated. CK20 and uroplakins were expressed in all superficial cells in postnatal urothelium. Their subcellular distribution characteristically changed in accordance with the progressive differentiati on of superficial cells. During the urothelial postnatal development, proli feration activity slowly decreases to the proliferatively quiescent urothel ium of the adult animal. Apoptosis is present in the first 9 postnatal days and within a few days of this period it appears simultaneously with desqua mation. Superficial urothelial cells gradually differentiate, which is refl ected in the changeable morphology of the apical plasma membrane.