Development of peptide-containing nerves in the human fetal vas deferens and seminal vesicle.

OBJECTIVE To use immunohistochemical methods to study the developing autonomic innervation of the human fetal vas deferens and seminal vesicle. MATERIAL AND METHODS Thirteen pre-natal specimens ranging in gestational age from 13 to 30 weeks were acquired following abortion or miscarriage. The overall innervation of each specimen was visualized using protein gene product 9.5 (PGP), a general nerve marker, while the onset and development of specific neuropeptide-containing sub-populations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene related peptide (CGRP), bombesin (BOM), somatostatin (SOM), and met-enkephalin (ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). RESULTS At 13 weeks numerous PGP, D beta H, TH, NPY and ENK immunoreactive (-IR) nerve trunks were present in the adventitia of the vas deferens and seminal vesicle but at this stage nerve fibres were not present in the smooth muscle coat of either organ. By 17 weeks, fine PGP-, D beta H, and TH-IR nerve fibres had penetrated the outer aspect of the muscle coat of the seminal vesicle but not the vas deferens. At 20 weeks a branching network of PGP-, D beta H- and TH-IR nerve fibres occurred throughout the full thickness of the muscle coat of the seminal vesicle while similar nerves were present only in the outer half of the muscle coat of the vas deferens. At 23 weeks the full thickness of the muscle coat of the vas deferens was richly innervated by a branching plexus of PGP-IR nerves. Many of these adventitial and intramuscular nerves were immunoreactive for D beta H or TH while some were immunoreactive for either NPY or ENK. Occasional adventitial nerves were immunoreactive for SP or CGRP, these being first observed at 20 weeks. VIP-IR nerves were extremely rare in the muscle coat of either organ, being first observed at 17 weeks in the seminal vesicle and at 20 weeks in the vas deferens where they mainly formed perivascular plexuses. PGP-IR nerves were first observed in the submucosa of the seminal vesicle at 20 weeks and in the vas deferens at 21 weeks. Some of these nerves were perivascular in location while other formed a subepithelial plexus which increased in density with increasing gestational age. At 22 weeks of gestation some of the submucosal nerves were immunoreactive for SP or NPY, while at 30 weeks NPY-IR nerves formed the majority of subepithelial nerves. Occasional VIP-IR subepithelial nerves were first observed at 26 weeks but were extremely rare even at 30 weeks. Submucosal nerves immunoreactive for CGRP, D beta H, TH or ENK did not occur in any of the specimens examined. CONCLUSION (i) From 13 weeks gestation autonomic nerves develop in the muscle coat of the fetal seminal vesicle and vas deferens, being denser in the seminal vesicle than the vas deferens up to 23 weeks gestation. (ii) The majority of the intramuscular nerves in either organ contain D beta H, TH, NPY and ENK and are presumably noradrenergic in type. (iii) A subepithelial nerve plexus develops around 20 weeks gestation and contains NPY but not VIP, unlike the adult organs. (iv) Scattered neuroendocrine cells immunoreactive for SOM are present in the mucosa of the seminal vesicle from 23 weeks of gestation.