DEVELOPMENT OF PEPTIDE-CONTAINING NERVES IN THE HUMAN FETAL PROSTATE-GLAND

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (1-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (DPH) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, 1-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and 1-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or 1-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and 1-ENK-IR nerves together with a few m-ENK-IR nerves. Occasional smooth muscle-associated varicose nerve fibres showed immunoreactivity for SP, CGRP, VIP or BOM although the majority of these types of nerve formed perivascular plexuses. Also at 26 wk numerous varicose nerve fibres were observed in association with the prostatic acini, the majority of such nerves containing NPY with a few showing immunoreactivity to VIP, 1-ENK, SP or CGRP. The relative paucity of VIP-IR nerves from the subepithelial plexus of the fetal prostatic acini is in marked contrast to the adult gland. Furthermore, unlike the situation in adults, PGP-IR ganglion cells were not present within the substance of any of the fetal prostate specimens included in this study. Randomly scattered endocrine-paracrine epithelial cells immunoreactive for CGRP were present in the prostatic glands and prostatic urethra at 13 wk gestation. Similar cells immunoreactive for BOM were first apparent in the prostatic and urethral epithelium at 20 wk. Occasional cells immunoreactive for SOM were first observed in the urethral epithelium at 22 wk and in the prostatic acini at 30 wk.