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         An official journal of the Society for Reproduction and Fertility. Learn more

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      Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium

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          Abstract

          Telocytes (TCs) have been described in various organs and species ( www.telocytes.com) as cells with telopodes (Tps) – very long cellular extensions with an alternation of thin segments (podomers) and dilated portions (podoms). We examined TCs using electron microscopy (EM), immunohistochemistry (IHC), immunofluorescence (IF), time-lapse videomicroscopy and whole-cell patch voltage clamp. EM showed a three-dimensional network of dichotomous-branching Tps, a labyrinthine system with homocellular and heterocellular junctions. Tps release extracellular vesicles (mean diameter of 160.6±6.9 nm in non-pregnant myometrium and 171.6±4.6 nm in pregnant myometrium), sending macromolecular signals to neighbouring cells. Comparative measurements (non-pregnant and pregnant myometrium) of podomer thickness revealed values of 81.94±1.77 vs 75.53±1.81 nm, while the podoms' diameters were 268.6±8.27 vs 316.38±17.56 nm. IHC as well as IF revealed double c-kit and CD34 positive results. Time-lapse videomicroscopy of cell culture showed dynamic interactions between Tps and myocytes. In non-pregnant myometrium, patch-clamp recordings of TCs revealed a hyperpolarisation-activated chloride inward current with calcium dependence and the absence of L-type calcium channels. TCs seem to have no excitable properties similar to the surrounding smooth muscle cells (SMCs). In conclusion, this study shows the presence of TCs as a distinct cell type in human non-pregnant and pregnant myometrium and describes morphometric differences between the two physiological states. In addition, we provide a preliminary in vitro electrophysiological evaluation of the non-pregnant state, suggesting that TCs could influence timing of the contractile activity of SMCs.

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          Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term.

          J. Norman, Bénédicte F. Jordan, Vicki Thomson … (2002)
          Accumulating evidence suggests that human parturition represents an inflammatory process. Leukocytes are known to infiltrate uterine tissues but the exact timing, nature and quantity of these cells has not been formally characterized. We have previously demonstrated an apparent increase in pro-inflammatory cytokines within tissues of the labouring uterus. The aims of this study were to quantify and compare the leukocyte subpopulations before and during labour in fetal membranes, decidua and cervix and to quantify and compare mRNA expression of interleukin-1beta (IL-1beta), IL-6, IL-8 and tumour necrosis factor-alpha in myometrium, cervix, chorio-decidua and amnion. Biopsies of each of these tissues were obtained from pregnant women delivered by Caesarean section before and after the onset of spontaneous labour at term. Subpopulations of leukocytes were identified using immunohistochemistry and cytokine mRNA expression was quantified using Northern analysis. We found that parturition was associated with a significant increase in IL-1beta, IL-6 and IL-8 mRNA expression in cervix and myometrium, IL-6 and IL-8 mRNA expression in chorio-decidua and IL-1beta and IL-8 mRNA expression in amnion. Histological analysis demonstrated that leukocytes (predominantly neutrophils and macrophages) infiltrate the uterine cervix coincident with the onset of labour. These data lend further support to the hypothesis that labour is an inflammatory process.
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            Macrophages infiltrate the human and rat decidua during term and preterm labor: evidence that decidual inflammation precedes labor.

            Sarah Hamilton, S. H. Lye, Oksana Shynlova … (2012)
            Preterm delivery is the leading cause of perinatal mortality and morbidity. Current tocolytics target myometrial contractions, a late step in the labor cascade. Identifying earlier events in parturition may lead to more effective therapeutic strategies. We hypothesized that inflammatory events in decidua (the maternal-fetal interface), characterized by leucocyte infiltration, are an early event during term and preterm labor (PTL). Leucocyte abundance in decidua of human pregnancies was quantified following term labor and PTL (idiopathic and infection associated), in conjunction with investigation of temporal inflammatory events in rat uterus during the perilabor period and in PTL induced by mifepristone. In human decidua, macrophage numbers were 4-fold higher in term labor (P < 0.01) and 2.5-fold higher in non-infection-associated PTL (P < 0.05) than in term nonlaboring samples. Neutrophil abundance was unchanged with labor but elevated in PTL with infection (5- to 53-fold increase; P < 0.01). T and NK cells were more abundant in idiopathic PTL than TL (P < 0.05). In rat, decidual macrophage infiltration increased 4.5-fold 12 h prior to labor and remained elevated during labor and early postpartum (P < 0.01). Decidual infiltration preceded that of the myometrium and was 4-fold higher (P < 0.01). In rat PTL, decidual macrophage numbers were also elevated (P < 0.01) and exceeded those of the myometrium (P < 0.05). These studies show for the first time that leucocytes infiltrate decidua during labor at term and preterm, supporting a role for leucocyte-derived inflammatory mediators in decidual activation. In the rat, this occurred prior to labor, suggesting it is an early event during parturition and thus a potential target for intervention.
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              Experimental acute myocardial infarction: telocytes involvement in neo-angiogenesis

              C Manole, V Cismaşiu, Mihaela Gherghiceanu … (2011)
              Abstract We used rat experimental myocardial infarction to study the ultrastructural recovery, especially neo-angiogenesis in the infarction border zone. We were interested in the possible role(s) of telocytes (TCs), a novel type of interstitial cell very recently discovered in myocardim (see http://www.telocytes.com). Electron microscopy, immunocytochemistry and analysis of several proangiogenic microRNAs provided evidence for TC involvement in neo-angiogenesis after myocardial infarction. Electron microscopy showed the close spatial association of TCs with neoangiogenetic elements. Higher resolution images provided the following information: (a) the intercellular space between the abluminal face of endothelium and its surrounding TCs is frequently less than 50 nm; (b) TCs establish multiple direct nanocontacts with endothelial cells, where the extracellular space seems obliterated; such nanocontacts have a length of 0.4–1.5 μm; (c) the absence of basal membrane on the abluminal face of endothelial cell. Besides the physical contacts (either nanoscopic or microscopic) TCs presumably contribute to neo-angiognesis via paracrine secretion (as shown by immunocytochemistry for VEGF or NOS2). Last but not least, TCs contain measurable quantities of angiogenic microRNAs (e.g. let-7e, 10a, 21, 27b, 100, 126-3p, 130a, 143, 155, 503). Taken together, the direct (physical) contact of TCs with endothelial tubes, as well as the indirect (chemical) positive influence within the ‘angiogenic zones’, suggests an important participation of TCs in neo-angiogenesis during the late stage of myocardial infarction.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Reproduction
                Journal ID (iso-abbrev): Reproduction
                Journal ID (publisher-id): REPRO
                Title: Reproduction (Cambridge, England)
                Publisher: BioScientifica (Bristol )
                ISSN (Print): 1470-1626
                ISSN (Electronic): 1741-7899
                Publication date (Print): April 2013
                Publication date (Electronic preprint): 20 October 2012
                Volume: 145
                Issue: 4
                Pages: 357-370
                Affiliations
                [1 ]Division of Cellular and Molecular Medicine , Carol Davila University of Medicine and Pharmacy , Bucharest, 050474, Romania
                [2 ]Department of Ultrastructural Pathology , Victor Babeş National Institute of Pathology , Bucharest, 050096, Romania
                [3 ]Department of Molecular Medicine , Victor Babeş National Institute of Pathology , Bucharest, 050096, Romania
                [4 ]Department of Anatomy Animal Physiology and Biophysics, Faculty of Biology , University of Bucharest , Bucharest, 050095, Romania
                [5 ]Department of Neurological Sciences (DSNNMM) , University of Verona , Verona, 37134, Italy
                [6 ]Division of Advanced Studies , Victor Babeş National Institute of Pathology , Bucharest 050096, Romania
                Author notes
                Correspondence should be addressed to L M Popescu at Division of Cellular and Molecular Medicine, Carol Davila University of Medicine and Pharmacy; Email: lmp@ 123456jcmm.org
                Article
                Publisher ID: REP120369
                DOI: 10.1530/REP-12-0369
                PMC ID: 3636525
                PubMed ID: 23404846
                SO-VID: c9984c9c-5cfc-4264-82dd-cd0af112feee
                Copyright © © 2013 Society for Reproduction and Fertility
                License:

                This is an Open Access article distributed under the terms of the Society for Reproduction and Fertility's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 September 2012
                Date revision received : 20 January 2013
                Date accepted : 29 January 2013
                Funding
                Funded by: Sectorial Operational Program Human Resources Development
                Award ID: POSDRU/89/1.5/S/58852
                Categories
                Subject: Research

                ScienceOpen disciplines: Obstetrics & Gynecology
                Data availability:
                ScienceOpen disciplines: Obstetrics & Gynecology

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