Telocytes damage in endometriosis‐affected rat oviduct and potential impact on fertility

Abstract

Women with endometriosis (EMs) have unexplained infertility. The recently identified telocytes (TCs) might participate in the maintenance of structural and functional integrity of oviduct tissue, but so far the involvement of TCs in EMs-affected oviduct tissue and potential impact on fertility capacity remain unknown. By an integrated technique of haematoxylin and eosin staining, in situ immunohistochemistry and double-labelled immunofluorescence staining and electron microscopy approach, TCs were studied in the autotransplantation Sprague–Dawley rat model of EMs-affected oviduct tissue and in sham control, respectively, together with determination of iNOS, COX-2, LPO and estradiol. TCs were found in perivascular connective tissue and smooth muscle bundles in sham oviduct, with typical ultrastructural features (a slender piriform/spindle/triangular cell body, and one or more extremely long prolongations, emerged from cell bodies and extend to various directions), and specific immunophenotype of CD34-positive/vimentin-positive/c-kit-negative. However, in EMs-affected oviduct tissue (grade III), extensive ultrastructural damage (degeneration, discontinue, dissolution and destruction), significant decrease or loss of TCs and interstitial fibrosis were observed, together with elevated level of iNOS, COX-2, LPO and estradiol, thus suggestive of inflammation and ischaemia-induced TCs damage. Based on TCs distribution and intercellular connections, we proposed that such damage might be involved in structural and functional abnormalities of oviduct, such as attenuated intercellular signalling and oviduct contractility, impaired immunoregulation and stem cell-mediated tissue repair, 3-D interstitial architectural derangement and tissue fibrosis. Therefore, TCs damage might provide a new explanation and potential target for EMs-induced tubal damage and fertility disorders.

Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis

“…Recently, TCs alterations in disease‐affected tissues were reported in fibrotic lesions of skin, cardiac, ulcerative colitis, Crohn's disease and gallstone disease . Furthermore, we have demonstrated that in endometriosis‐affected oviduct tissues, ultrastructural damage and significant loss of TCs might contribute to interstitial fibrosis and subsequent oviduct dysfunction . Nevertheless, whether AS also caused TCs damage and led to structural and functional abnormalities of oviduct, further engaged in poor reproductive outcome, need more detailed evidence.…”

“…On the basis of our previous observations , the current hypothesis is that, in exposure to acute inflammatory, oviduct TCs underwent cell damage and cause structural alterations, further induce functional abnormalities of oviduct. In support to this hypothesis, we conduct a comparative study on ultrastructural damage of TCs in SD rat model of AS‐affected and ‐unaffected oviduct tissues, respectively, together with determination of inflammatory state.…”

Telocytes in minor salivary glands of primary Sjögren's syndrome: association with the extent of inflammation and ectopic lymphoid neogenesis

“…The unique phenotype, ultrastructural characteristics, tissue distribution and multiple intercellular connections of telocytes, as well their putative role in local immune surveillance and homeostasis , raised the possibility of their involvement in the pathogenesis of inflammatory/autoimmune disorders. In this setting, numerical and structural abnormalities of this cell subset have been described in human CD, UC and SSc, as well as in experimental endometriosis . Taken that fibrosis following inflammation is a common hallmark in target tissues of these diseases, it has been speculated that telocyte entrapment in the fibrotic matrix may be one of the causes of their damage and progressive reduction in such scenarios .…”

Telocytes in female reproductive system (human and animal)

“…For instance, rat uterus tissue contains different types of immune positive TCs: c‐kit (−)/vimentin (+), c‐kit (+)/vimentin (+), c‐kit (+)/CD34 (+). This range might be basis of region‐specific TCs roles .…”