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Reproductive Sciences

, Volume 18, Issue 12, pp 1237–1245 | Cite as

Adaptive Plasticity of Vaginal Innervation in Term Pregnant Rats

  • Zhaohui Liao
  • Peter G. SmithEmail author
Original Articles

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.

Keywords

autonomic innervation estrous cycle parturition sensory innervation 

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References

  1. 1.
    Zoubina EV, Smith PG. Axonal degeneration and regeneration in rat uterus during the estrous cycle. Autonom Neurosci. 2000;84(3):176–185.Google Scholar
  2. 2.
    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.Google Scholar
  3. 3.
    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.Google Scholar
  4. 4.
    MacLean AB, Nicol LA, Hodgins MB. Immunohistochemical localization of estrogen receptors in the vulva and vagina. J Reprod Med. 1990;35(11):1015.Google Scholar
  5. 5.
    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.Google Scholar
  6. 6.
    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.Google Scholar
  7. 7.
    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.Google Scholar
  8. 8.
    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.Google Scholar
  9. 9.
    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.Google Scholar
  10. 10.
    Zoubina EV, Fan Q, Smith PG. Variations in uterine innervation during the estrous cycle in rat. J Comp Neurol. 1998;397(4):561–571.Google Scholar
  11. 11.
    Brauer MM. Cellular and molecular mechanisms underlying plasticity in uterine sympathetic nerves. Auton Neurosci. 2008;140(1–2):1–16.Google Scholar
  12. 12.
    Latini C, Frontini A, Morroni M, Marzioni D, Castellucci M, Smith PG. Remodeling of uterine innervation. Cell Tissue Res. 2008;334(1):1–6.Google Scholar
  13. 13.
    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.Google Scholar
  14. 14.
    Ting AY, Blacklock AD, Smith PG. Estrogen regulates vaginal sensory and autonomic nerve density in the rat. Biol Reprod. 2004;71(4):1397–1404.Google Scholar
  15. 15.
    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.Google Scholar
  16. 16.
    Ghatei MA, Gu J, Mulderry PK, et al. Calcitonin gene-related peptide (CGRP) in the female rat urogenital tract. Peptides. 1985;6(5):809.Google Scholar
  17. 17.
    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.Google Scholar
  18. 18.
    Long JA, Evans HM. The oestrus cycle in the rat and associated fenomena. Mem Univ Calif. 1922;6:1.Google Scholar
  19. 19.
    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.Google Scholar
  20. 20.
    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.Google Scholar
  21. 21.
    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.Google Scholar
  22. 22.
    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.Google Scholar
  23. 23.
    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.Google Scholar
  24. 24.
    Ross R, Klebig ML. Fine structural changes in uterine smooth muscle and fibroblasts in response to estrogen. J Cell Biol. 1967;32(1):155.Google Scholar
  25. 25.
    Zoubina EV, Smith PG. Uterine sympathetic hyperinnervation in the estrogen receptor α knock-out mouse. Neuroscience. 2001;103(1):237–244.Google Scholar
  26. 26.
    Cason AM, Samuelsen CL, Berkley KJ. Estrous changes in vaginal nociception in a rat model of endometriosis. Horm Behav. 2003;44(2):123–131.Google Scholar
  27. 27.
    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.Google Scholar
  28. 28.
    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.Google Scholar
  29. 29.
    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.Google Scholar
  30. 30.
    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.Google Scholar
  31. 31.
    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.Google Scholar
  32. 32.
    Taya K, Greenwald GS. In vivo and in vitro ovarian steroidogenesis in the pregnant rat. Biol Reprod. 1981;25(4):683.Google Scholar
  33. 33.
    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.Google Scholar
  34. 34.
    Gunn JA, Franklin KJ. The sympathetic innervation of the vagina. Proc Royal Soc London Ser B. 1922;94(669):197–203.Google Scholar
  35. 35.
    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.Google Scholar
  36. 36.
    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.Google Scholar
  37. 37.
    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.Google Scholar
  38. 38.
    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.Google Scholar
  39. 39.
    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.Google Scholar
  40. 40.
    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.Google Scholar
  41. 41.
    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.Google Scholar
  42. 42.
    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.Google Scholar
  43. 43.
    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.Google Scholar
  44. 44.
    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.Google Scholar
  45. 45.
    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.Google Scholar
  46. 46.
    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.Google Scholar
  47. 47.
    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.Google Scholar
  48. 48.
    Immke DC, Gavva NR. The TRPV1 receptor and nociception. Semin Cell Dev Biol. 2006;17(5):582–591.Google Scholar

Copyright information

© Society for Reproductive Investigation 2011

Authors and Affiliations

  1. 1.Institute for Neurological DisordersUniversity of Kansas Medical CenterKansas CityUSA
  2. 2.Kansas Intellectual and Developmental Disabilities Research CenterUniversity of Kansas Medical CenterKansas CityUSA
  3. 3.Department of Molecular and Integrative PhysiologyUniversity of Kansas Medical CenterKansas CityUSA
  4. 4.Hemenway Life Sciences Innovation CenterUniversity of Kansas Medical CenterKansas CityUSA

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