IMMUNOHISTOCHEMICAL LOCALIZATION OF NEUROMARKERS AND NEUROPEPTIDES INHUMAN FETAL AND NEONATAL URINARY-BLADDER

Objective To use immunohistochemical techniques to determine the spati al and temporal distribution of a variety of neuropeptides in the huma n fetal and neonatal urinary bladder. Materials and methods Thirteen p re-natal specimens ranging in gestational age from 17 to 35 weeks were acquired following abortion or miscarriage. In addition two post-nata l specimens aged 8 and 12 weeks were obtained at post-mortem and were included in this study. The overall innervation of each specimen was v isualized using the general nerve marker protein gene product 9.5 (PGP ). Localization of dopamine-and hydroxylase (DBH) and tyrosine hydroxy lase (TH) revealed putative noradrenergic nerves. The neuropeptides st udied included neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP). Results At 17 weeks a rich plexus of PGP and NPY-containing nerves was present throughout the detrusor muscle coat. As gestational age incre ased, VIP, SP and CGRP-containing nerves were observed with increasing frequency although SP and CGRP were mainly confined to perivascular n erve plexuses. TH- and DBH-containing nerves were first observed in th e intramural ureters at 30 weeks and the detrusor muscle at 35 weeks a nd were relatively numerous in the intramural meters and muscle of the superficial trigone in the two post-natal specimens. PGP-containing n erves were first observed beneath the bladder epithelium at 23 weeks a nd gradually became more numerous with increasing age. Occasional NPY, VIP, SP and CGRP-containing nerves were observed in the submucosa but TH- and DBB-immunostained nerves were especially numerous in the muco sa of the trigone in the two post-natal specimens, many such nerves be ing unrelated to the vascular supply. Conclusions The bladder detrusor possesses a rich autonomic innervation by 17 weeks of gestation and t his presumptive cholinergic innervation is associated with NPY immunor eactivity. Presumptive noradrenergic nerves appear relatively late in pre-natal development and mainly supply the intramural meters and supe rficial trigone. ii submucosal plexus of nerves has been demonstrated, the functional significance of which remains uncertain.