Morphological and neurochemical differences in peptidergic nerve fibers of the mouse vagina.
The vagina is innervated by a complex arrangement of sensory, sympathetic, and parasympathetic nerve fibers that contain classical transmitters plus an array of neuropeptides and enzymes known to regulate diverse processes including blood flow and nociception. The neurochemical characteristics and distributions of peptide-containing nerves in the mouse vagina are unknown. This study used multiple labeling immunohistochemistry, confocal maging and analysis to investigate the presence and colocalization of the peptides vasoactive intestinal polypeptide (VIP), calcitonin-gene related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and the nitric oxide synthesizing enzyme neuronal nitric oxide synthase (nNOS) in nerve fibers of the murine vaginal wall. We compared cervical and vulvar areas of the vagina in young nullipara and older multipara C57Bl/6 mice, and identified differences including that small ganglia were restricted to cervical segments, epithelial fibers were mainly present in vulvar segments and most nerve fibers were found in the lamina propria of the cervical region of the vagina, where a higher number of fibers containing immunoreactivity for VIP, CGRP, SP, or nNOS were found. Two populations of VIP-containing fibers were identified: fibers containing CGRP and fibers containing VIP but not CGRP. Differences between young and older mice were present in multiple layers of the vaginal wall, with older mice showing overall loss of innervation of epithelium of the proximal vagina and reduced proportions of VIP, CGRP, and SP containing nerve fibers in the distal epithelium. The distal vagina also showed increased vascularization and perivascular fibers containing NPY. Immunolabeling of ganglia associated with the vagina indicated the likely origin of some peptidergic fibers. Our results reveal regional differences and age- or parity-related changes in innervation of the mouse vagina, effecting the distribution of neuropeptides with diverse roles in function of the female genital tract.
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
Christine M
http://orcid.org/0000-0002-5227-3524
CM
Barry
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
Esther
E
Ji
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
Harman
H
Sharma
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
Lara
L
Beukes
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
Patricia I
PI
Vilimas
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
Yvette C
YC
DeGraaf
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
Dusan
D
Matusica
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
Rainer V
RV
Haberberger
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis* / Q000378:metabolism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000737:chemistry* / Q000378:metabolism; D009478:Neuropeptide Y / Q000032:analysis* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000032:analysis / Q000378:metabolism; D013373:Substance P / Q000032:analysis* / Q000378:metabolism; D014621:Vagina / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000032:analysis* / Q000378:metabolism
D009478:Neuropeptide Y; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D015740:Calcitonin Gene-Related Peptide
RRID: AB_11210984; RRID: AB_2307354; RRID: AB_2313685; RRID: AB_2314176; RRID: AB_476701; RRID: AB_572266; calcitonin gene-related peptide; neuropeptide tyrosine; substance P; vaginal innervation; vasoactive intestinal polypeptide