Estrogen regulates vaginal sensory and autonomic nerve density in the rat

Alison Y. Ting, Audrey D. Blacklock, Peter G. Smith

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Vaginal function is strongly influenced by reproductive hormone status. Vaginal dysfunction during menopause is generally assumed to occur because of diminished estrogen-mediated trophic support of vaginal target cells. However, peripheral neurons possess estrogen receptors and are potentially responsive to gonadal steroid hormones. In the present study, we investigated whether sensory and autonomic innervation of the vagina varies among rats during the estrus phase of the estrous cycle, following chronic ovariectomy, and after sustained estrogen replacement. Relative to rats in estrus, ovariectomized rats showed a 59% elevation in nerve density, as determined using the panneuronal marker PGP 9.5. This increase persisted even after correcting for differences in vaginal tissue size, indicating true axonal proliferation after ovariectomy rather than changes secondary to altered volume. Increased total innervation after ovariectomy was attributable to increased densities of sympathetic nerves immunostained for tyrosine hydroxylase (70%), cholinergic parasympathetic nerves immunoreactive for vesicular acetylcholine transporter (93%), and calcitonin gene-related peptide-immunoreactive sensory nociceptor nerves (84%). Myelinated primary sensory innervation revealed by RT-97 immunoreactivity did not appear to be affected. Sustained 17β-estradiol administration reduced innervation density to an extent comparable to that of estrus, implying that estrogen is the hormone mediating vaginal neuroplasticity. These findings indicate that some aspects of vaginal dysfunction during menopause may be attributable to changes in innervation. Increased sympathetic innervation may augment vasoconstriction and promote vaginal dryness, while sensory nociceptor axon proliferation may contribute to symptoms of pain, burning, and itching associated with menopause and some forms of vulvodynia.

Original languageEnglish (US)
Pages (from-to)1397-1404
Number of pages8
JournalBiology of reproduction
Issue number4
StatePublished - Oct 2004
Externally publishedYes


  • Estradiol
  • Neurotransmitters
  • Ovulatory cycle
  • Steroid hormones
  • Vagina

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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