Adaptive Plasticity of Vaginal Innervation in Term Pregnant Rats

In: Reproductive Sciences · 2011 · vol. 18(12) , pp. 1237–1245 · doi:10.1177/1933719111410706 · PMID:21666101 · W1997247365
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Vaginal innervation, including PGP 9.5, sympathetic, parasympathetic, and sensory axons, significantly decreases in late-term pregnant rats compared to non-pregnant rats.

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Abstract

Changes in reproductive status place varied functional demands on the vagina. These include receptivity to male intromission and sperm transport in estrus, barrier functions during early pregnancy, and providing a conduit for fetal passage at parturition. Peripheral innervation regulates vaginal function, which in turn may be influenced by circulating reproductive hormones. We assessed vaginal innervation in diestrus and estrus (before and after the estrous cycle surge in estrogen), and in the early (low estrogen) and late (high estrogen) stages in pregnancy. In vaginal sections from cycling rats, axons immunoreactive for the pan-neuronal marker protein gene product 9.5 (PGP 9.5) showed a small reduction at estrus relative to diestrus, but this difference did not persist after correcting for changes in target size. No changes were detected in axons immunoreactive for tyrosine hydroxylase (sympathetic), vesicular acetylcholine transporter (parasympathetic), or calcitonin gene-related peptide and transient receptor potential vanilloid type 1 (TRPV-1; sensory nociceptors). In rats at 10 days of pregnancy, innervation was similar to that observed in cycling rats. However, at 21 days of pregnancy, axons immunoreactive for PGP 9.5 and each of the subpopulation-selective markers were significantly reduced both when expressed as percentage of sectional area or after correcting for changes in target size. Because peripheral nerves regulate vaginal smooth muscle tone, blood flow, and pain sensitivity, reductions in innervation may represent important adaptive mechanisms facilitating parturition.
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Abstract

Changes in reproductive status place varied functional demands on the vagina. These include receptivity to male intromission and sperm transport in estrus, barrier functions during early pregnancy, and providing a conduit for fetal passage at parturition. Peripheral innervation regulates vaginal function, which in turn may be influenced by circulating reproductive hormones. We assessed vaginal innervation in diestrus and estrus (before and after the estrous cycle surge in estrogen), and in the early (low estrogen) and late (high estrogen) stages in pregnancy. In vaginal sections from cycling rats, axons immunoreactive for the pan-neuronal marker protein gene product 9.5 (PGP 9.5) showed a small reduction at estrus relative to diestrus, but this difference did not persist after correcting for changes in target size. No changes were detected in axons immunoreactive for tyrosine hydroxylase (sympathetic), vesicular acetylcholine transporter (parasympathetic), or calcitonin gene-related peptide and transient receptor potential vanilloid type 1 (TRPV-1; sensory nociceptors). In rats at 10 days of pregnancy, innervation was similar to that observed in cycling rats. However, at 21 days of pregnancy, axons immunoreactive for PGP 9.5 and each of the subpopulation-selective markers were significantly reduced both when expressed as percentage of sectional area or after correcting for changes in target size. Because peripheral nerves regulate vaginal smooth muscle tone, blood flow, and pain sensitivity, reductions in innervation may represent important adaptive mechanisms facilitating parturition. Similar content being viewed by others

References

Zoubina EV, Smith PG. Axonal degeneration and regeneration in rat uterus during the estrous cycle. Autonom Neurosci. 2000;84(3):176–185. Dong Y, Chen Y, Wang Z, Naito J, Chen J-L. Role of sympathetic nerves on early embryonic development and immune modulation of uterus in pregnant mice. Auton Neurosci. 2007;131(1–2):87–93. Ohta Y, Sato T, Iguchi T. Immunocytochemical localization of progesterone receptor in the reproductive tract of adult female rats. Biol Reprod. 1993;48(1):205–213. MacLean AB, Nicol LA, Hodgins MB. Immunohistochemical localization of estrogen receptors in the vulva and vagina. J Reprod Med. 1990;35(11):1015. Buchanan DL, Kurita T, Taylor JA, Lubahn DB, Cunha GR, Cooke PS. Role of stromal and epithelial estrogen receptors in vaginal epithelial proliferation, stratification, and cornification. Endocrinology. 1998;139(10):4345–4352. Munarriz R, Kim SW, Kim NN, Traish A, Goldstein I. A review of the physiology and pharmacology of peripheral (vaginal and clitoral) female genital arousal in the animal model. J Urol. 2003;170(2)(pt 2):S40–S44. Sporrong B, Alm P, Owman C, Sjoberg NO, Thorbert G. Ultrastructural evidence for adrenergic nerve degeneration in the guinea pig uterus during pregnancy. Cell Tissue Res. 1978;195(1):189. Thorbert G, Alm P, Owman C, Sjoberg NO, Sporrong B. Regional changes in structural and functional integrity of myometrial adrenergic nerves in pregnant guinea-pig, and their relationship to the localization of the conceptus. Acta Physiol Scand. 1978;103(2):120. Owman C, Alm P, Björklund A, Thorbert G. Extensive sympathetic denervation of the uterus during pregnancy as evidenced by tyrosine hydroxylase determinations in the guinea pig. Adv Biochem Psychopharmacol. 1980;25:313–320. Zoubina EV, Fan Q, Smith PG. Variations in uterine innervation during the estrous cycle in rat. J Comp Neurol. 1998;397(4):561–571. Brauer MM. Cellular and molecular mechanisms underlying plasticity in uterine sympathetic nerves. Auton Neurosci. 2008;140(1–2):1–16. Latini C, Frontini A, Morroni M, Marzioni D, Castellucci M, Smith PG. Remodeling of uterine innervation. Cell Tissue Res. 2008;334(1):1–6. Klukovits A, Gaspar R, Santha P, Jancso G, Falkay G. Functional and histochemical characterization of a uterine adrenergic denervation process in pregnant rats. Biol Reprod. 2002;67(3):1013–1017. Ting AY, Blacklock AD, Smith PG. Estrogen regulates vaginal sensory and autonomic nerve density in the rat. Biol Reprod. 2004;71(4):1397–1404. Giraldi A, Alm P, Werkstrom V, Myllymaki L, Wagner G, Andersson KE. Morphological and functional characterization of a rat vaginal smooth muscle sphincter. Int J Impot Res. 2002;14(4):271. Ghatei MA, Gu J, Mulderry PK, et al. Calcitonin gene-related peptide (CGRP) in the female rat urogenital tract. Peptides. 1985;6(5):809. Berkley KJ, Robbins A, Sato Y. Functional differences between afferent fibers in the hypogastric and pelvic nerves innervating female reproductive organs in the rat. J Neurophysiol. 1993;69(2):533. Long JA, Evans HM. The oestrus cycle in the rat and associated fenomena. Mem Univ Calif. 1922;6:1. Freeman ME, Knobil E, Neil J, (eds). Neuroendocrine control of the ovarian cycle of the rat. The Physiology of Reproduction. New York, NY: Raven Press; 1988:1893. Bridges RS. A quantitative analysis of the roles of dosage, sequence, and duration of estradiol and progesterone exposure in the regulation of maternal behavior in the rat. Endocrinology. 1984;114(3):930. Wang H, Eriksson H, Sahlin L. Estrogen receptors alpha and beta in the female reproductive tract of the rat during the estrous cycle. Biol Reprod. 2000;63(5):1331–1340. Spornitz UM, Rinderknecht BP, Edelmann A, Scheidegger B, Cairoli F. Ultrastructure as a basis for dating of rat endometrium. Anat Rec. 1994;238(2):163. Centola GM. Surface features of exfoliated vaginal epithelial cells during the oestrous cycle of the rat examined by scanning electron microscopy. J Anat. 1978;127(pt 3):553–561. Ross R, Klebig ML. Fine structural changes in uterine smooth muscle and fibroblasts in response to estrogen. J Cell Biol. 1967;32(1):155. Zoubina EV, Smith PG. Uterine sympathetic hyperinnervation in the estrogen receptor α knock-out mouse. Neuroscience. 2001;103(1):237–244. Cason AM, Samuelsen CL, Berkley KJ. Estrous changes in vaginal nociception in a rat model of endometriosis. Horm Behav. 2003;44(2):123–131. Dangoor D, Giladi E, Fridkin M, Gozes I. Neuropeptide receptor transcripts are expressed in the rat clitoris and oscillate during the estrus cycle in the rat vagina. Peptides. 2005;26(12):2579–2584. Daucher JA, Clark KA, Stolz DB, Meyn LA, Moalli PA. Adaptations of the rat vagina in pregnancy to accommodate delivery. Obstet Gynecol. 2007;109(1):128–135. Rahn DD, Acevedo JF, Word RA. Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse. Am J Physiol Regul Integr Comp Physiol. 2008;295(4):R1351–R1358. Pessina MA, Hoyt RF, Goldstein I, Traish AM. Differential effects of estradiol, progesterone, and testosterone on vaginal structural integrity. Endocrinology. 2006;147(1):61–69. Zoubina EV, Mize AL, Alper RH, Smith PG. Acute and chronic estrogen supplementation decreases uterine sympathetic innervation in ovariectomized adult virgin rats. Histol Histopathol. 2001;16(4):989–996. Taya K, Greenwald GS. In vivo and in vitro ovarian steroidogenesis in the pregnant rat. Biol Reprod. 1981;25(4):683. Manabe Y, Yoshida Y. Collagenolysis in human vaginal tissue during pregnancy and delivery: a light and electron microscopic study. Am J Obstet Gynecol. 1986;155(5):1060–1066. Gunn JA, Franklin KJ. The sympathetic innervation of the vagina. Proc Royal Soc London Ser B. 1922;94(669):197–203. Liu S, Sato K, Kobayashi T, Yamada T, Kageyama Y, Kihara K. Sympathetic efferent pathways projecting to the vagina in the dog. Auton Neurosci. 2001;88(1–2):45–51. Oh SJ, Hong SK, Kim SW, Paick JS. Histological and functional aspects of different regions of the rabbit vagina. Int J Impot Res. 2003;15(2):142–150. Kim SW, Kim NN, Jeong SJ, Munarriz R, Goldstein I, Traish AM. Modulation of rat vaginal blood flow and estrogen receptor by estradiol. J Urol. 2004;172(4)(pt 1):1538–1543. Persson K, Alm P, Uvelius B, Andersson KE. Nitrergic and cholinergic innervation of the rat lower urinary tract after pelvic ganglionectomy. Am J Physiol. 1998;274(2 pt):R389–R397. Al-Hijji J, Larsson B, Batra S. Nitric oxide synthase in the rabbit uterus and vagina: hormonal regulation and functional significance. Biol Reprod. 2000;62(5):1387–1392. Hoyle CH, Stones RW, Robson T, Whitley K, Burnstock G. Innervation of vasculature and microvasculature of the human vagina by NOS and neuropeptide-containing nerves. J Anat. 1996;188(Pt 3):633–644. Basha M, LaBelle EF, Northington GM, Wang T, Wein AJ, Chacko S. Functional significance of muscarinic receptor expression within the proximal and distal rat vagina. Am J Physiol Regul Integr Comp Physiol. 2009;297(5):R1486–R1493. Shew RL, Papka RE, McNeill DL. Calcitonin gene-related peptide in the rat uterus: presence in nerves and effects on uterine contraction. Peptides. 1990;11(3):583–589. Ziessen T, Moncada S, Cellek S. Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall. Br J Pharmacol. 2002;135(2):546–554. Giraldi A, Persson K, Werkstrom V, Alm P, Wagner G, Andersson KE. Effects of diabetes on neurotransmission in rat vaginal smooth muscle. Int J Impot Res. 2001;13(2):58–66. Pinter E, Szolcsanyi J. Plasma extravasation in the skin and pelvic organs evoked by antidromic stimulation of the lumbosacral dorsal roots of the rat. Neuroscience. 1995;68(2):603–614. Mowa CN, Usip S, Collins J, Storey-Workley M, Hargreaves KM, Papka RE. The effects of pregnancy and estrogen on the expression of calcitonin gene-related peptide (CGRP) in the uterine cervix, dorsal root ganglia and spinal cord. Peptides. 2003;24(8):1163–1174. Ishida-Yamamoto A, Senba E. Cell types and axonal sizes of calcitonin gene-related peptide-containing primary sensory neurons of the rat. Brain Res Bull. 1990;24(6):759–764. Immke DC, Gavva NR. The TRPV1 receptor and nociception. Semin Cell Dev Biol. 2006;17(5):582–591. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Liao, Z., Smith, P.G. Adaptive Plasticity of Vaginal Innervation in Term Pregnant Rats. Reprod. Sci. 18, 1237–1245 (2011). https://doi.org/10.1177/1933719111410706 Published: Issue date: DOI: https://doi.org/10.1177/1933719111410706

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