The Autonomic Innervation and Uterine Telocyte Interplay in Leiomyoma Formation

Cell Transplant. 2019 May;28(5):619-629. doi: 10.1177/0963689719833303. Epub 2019 Mar 6.

Abstract

The autonomic innervation of the uterus is involved in multiple pathophysiological processes in both humans and animals. Pathological conditions such as adenomyosis or inflammatory pelvic disease are usually accompanied by significant alterations in uterine innervation. In the current study, we focused on autonomic innervation of uterine fibroids, the identification of recently described interstitial cells, telocytes, and the possible interplay between these structures. In this work, uterine telocytes were identified by immunopositivity for c-kit, CD34, and PDGFRα. Nerves were revealed by immunolabeling for neuronal markers: protein gene product PGP 9.5, inducible nitric oxide synthase (iNOS), choline acetyltransferase (ChAT), and tyrosine hydroxylase (TH). The gross organization of myometrial tissue has been analyzed by routine histology. The results demonstrated that the density of iNOS and ChAT-immunopositive neurons in the uterine fibroids was higher than that in the control samples. The density of telocytes in the fibrosis foci was lower than that in the normal myometrium. Our results suggest that autonomic innervation and telocytes are involved in the microenvironment imbalance characteristic of uterine leiomyoma. Since NOS-positive nerves play an important role in oxidative stress modulation, they might lead to a decrease in the number of telocytes, which are crucial components in the pathogenesis of leiomyoma formation.

Keywords: PDGFRα; leiomyoma; nitric oxide synthase (NOS); protein gene product 9.5 (PGP 9.5); telocytes.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD34 / analysis
  • Female
  • Humans
  • Leiomyoma / pathology*
  • Middle Aged
  • Nitric Oxide Synthase / analysis
  • Proto-Oncogene Proteins c-kit / analysis
  • Receptor, Platelet-Derived Growth Factor alpha / analysis
  • Telocytes / pathology*
  • Uterine Neoplasms / pathology*
  • Uterus / innervation
  • Uterus / pathology*

Substances

  • Antigens, CD34
  • Nitric Oxide Synthase
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha