Barry Christine M, Ji Esther, Sharma Harman, Beukes Lara, Vilimas Patricia I, DeGraaf Yvette C, Matusica Dusan, Haberberger Rainer V
Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, Australia.
J Comp Neurol. 2017 Jul 1;525(10):2394-2410. doi: 10.1002/cne.24214. Epub 2017 Apr 18.
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.
阴道由感觉神经、交感神经和副交感神经纤维的复杂排列支配，这些神经纤维包含经典递质以及一系列已知可调节包括血流和痛觉在内的多种过程的神经肽和酶。小鼠阴道中含肽神经的神经化学特征和分布尚不清楚。本研究使用多重标记免疫组织化学、共聚焦成像和分析来研究血管活性肠肽（VIP）、降钙素基因相关肽（CGRP）、P物质（SP）、神经肽Y（NPY）以及一氧化氮合成酶神经元型一氧化氮合酶（nNOS）在小鼠阴道壁神经纤维中的存在和共定位。我们比较了年轻未生育和年长经产C57Bl/6小鼠阴道的宫颈和外阴区域，发现了一些差异，包括小神经节仅限于宫颈段，上皮纤维主要存在于外阴段，并且大多数神经纤维位于阴道宫颈区域的固有层，在该区域发现了更多含有VIP、CGRP、SP或nNOS免疫反应性的纤维。鉴定出了两类含VIP的纤维：含CGRP的纤维和含VIP但不含CGRP的纤维。年轻和年长小鼠在阴道壁的多层中存在差异，年长小鼠近端阴道上皮的神经支配总体丧失，远端上皮中含VIP、CGRP和SP的神经纤维比例降低。阴道远端还显示血管生成增加以及含NPY的血管周围纤维。与阴道相关的神经节的免疫标记表明了一些肽能纤维的可能起源。我们的结果揭示了小鼠阴道神经支配的区域差异以及与年龄或生育相关的变化，影响了在女性生殖道功能中具有不同作用的神经肽的分布。
