{"paper_id":"94ebbba1-1edc-4bbf-9f0c-2174867f77ec","body_text":"Abstract\nTelocytes (TCs) are interstitial cells characterized by long, thin cytoplasmic extensions called telopodes. Although their presence has been established in various organs, data on their existence and organization within the human ovary remain limited. This study aimed to identify and describe telocytes in the ovarian stroma using immunohistochemical, immunofluorescence, and ultrastructural methods. Ovarian tissues from women aged 24–65 years who underwent total hysterectomy and bilateral salpingo-oophorectomy for nonmalignant uterine diseases were analyzed. TCs were identified by CD34 co-expression with c-KIT, vimentin, platelet-derived growth factor receptor (PDGFR)-β, and alpha-smooth muscle actin (α-SMA) and confirmed by transmission electron microscopy with immunogold labeling. The results demonstrated that telocytes form two to three discontinuous layers around the adventitia of large and medium-sized blood vessels and establish close contacts with stromal components, including smooth muscle cells. This spatial organization suggests their involvement in intercellular communication and stromal coordination within the ovarian microenvironment. These findings provide the first ultrastructural and immunohistochemical evidence of telocytes in the human ovarian stroma and highlight the need for further studies to clarify their physiological and pathological roles in ovarian function, including potential morphological and molecular differences among females of different age groups.\nSimilar content being viewed by others\nData availability\nNo datasets were generated or analyzed during the current study.\nReferences\nAbd-Elkareem M (2017) Cell-specific immuno-localization of progesterone receptor alpha in the rabbit ovary during pregnancy and after parturition. Anim Reprod Sci 180:100–120. https://doi.org/10.1016/j.anireprosci.2017.03.007\nAwad M, Gaber W, Ibrahim D (2019) Onset of appearance and potential significance of telocytes in the developing fetal lung. Microsc Microanal 25:1246–1256. https://doi.org/10.1017/S1431927619014922\nBei Y, Wang F, Yang C, Xiao J (2015) Telocytes in regenerative medicine. J Cell Mol Med 19:1441–1454. https://doi.org/10.1111/jcmm.12594\nBojin FM, Gavriliuc OI, Cristea MI, Tanasie G, Tatu CS, Panaitescu C, Paunescu V (2011) Telocytes within human skeletal muscle stem cell niche. J Cell Mol Med 15:2269–2272. https://doi.org/10.1111/j.1582-4934.2011.01386.x\nCapel B (2014) Ovarian epithelium regeneration by Lgr5+ cells. Nat Cell Biol 16:743–744. https://doi.org/10.1038/ncb3020\nCismasiu VB, Popescu LM (2015) Telocytes transfer extracellular vesicles loaded with microRNAs to stem cells. J Cell Mol Med 19:351–358. https://doi.org/10.1111/jcmm.12529\nCretoiu SM, Popescu LM (2014) Telocytes revisited. Biomol Concepts 5:353–369. https://doi.org/10.1515/bmc-2014-0029\nCretoiu SM, Cretoiu D, Simionescu A, Popescu LM (2011) Telocytes in human Fallopian tube and uterus express estrogen and progesterone receptors. IntechOpen\nCreţoiu SM, Creţoiu D, Popescu LM (2012) Human myometrium—the ultrastructural 3D network of telocytes. J Cell Mol Med 16:2844–2849. https://doi.org/10.1111/j.1582-4934.2012.01651.x\nDelibaş Ö, Ünver Saraydın S (2020) Morphology and functions of telocytes. Kafkas J Med Sci 10:161–170. https://doi.org/10.5505/kjms.2020.25986\nDuquette RA, Shmygol A, Vaillant C, Mobasheri A, Pope M, Burdyga T, Wray S (2005) Vimentin-positive, c-KIT-negative interstitial cells in human and rat uterus: a role in pacemaking? Biol Reprod 72:276–283. https://doi.org/10.1095/biolreprod.104.033506\nFamiliari G, Makabe S, Motta P (1991) Ultrastructure of the ovary. Springer, 340 pp. Nijhoff/Kluwer Boston\nFan X, Bialecka M, Moustakas I et al (2019) Single-cell reconstruction of follicular remodeling in the human adult ovary. Nat Commun 10:3164. https://doi.org/10.1038/s41467-019-11036-9\nFaussone-Pellegrini MS, Gherghiceanu M (2016) Telocyte’s contacts. Semin Cell Dev Biol 55:3–8. https://doi.org/10.1016/j.semcdb.2016.01.036\nGartner LP (2014) Color Atlas and Text of Histology, 7th edn. Wolters Kluwer.\nHadrian M, Kinnear MK, Tomaszewski CE, Chang AL, Moravek MB, Xu M, Padmanabhan V, Shikanov A (2020) The ovarian stroma as a new frontier. Reproduction 160:R25–R39. https://doi.org/10.1530/REP-19-0501\nHussein MT, Abdel-Maksoud FM (2020) Structural investigation of epididymal microvasculature and its relation to telocytes and immune cells in camel. Microsc Microanal 26:1024–1034. https://doi.org/10.1017/S1431927620001786\nKlein M, Csöbönyeiová M, Danišovič L, Lapides L, Varga I (2022) Telocytes in the female reproductive system: up-to-date knowledge, challenges and possible clinical applications. Life 12:267. https://doi.org/10.3390/life12020267\nKondo A, Kaestner KH (2019) Emerging diverse roles of telocytes. Development 146:175018. https://doi.org/10.1242/dev.175018\nLi YY, Zhang S, Li YG, Wang Y (2016) Isolation, culture, purification and ultrastructural investigation of cardiac telocytes. Mol Med Rep 14:1194–1200. https://doi.org/10.3892/mmr.2016.5386\nLiu T, Wang S, Li Q et al (2016) Telocytes as potential targets in a cyclophosphamide-induced animal model of premature ovarian failure. Mol Med Rep 14:2415–2422. https://doi.org/10.3892/mmr.2016.5540\nMazzoni TS, Viadanna RR, Quagio-Grassiotto I (2019) Presence, localization and morphology of TELOCYTES in developmental gonads of fishes. J Morphol 280:654–665. https://doi.org/10.1002/jmor.20972\nMohamedien D, Mokhtar DM, Abdellah N et al (2023) Ovary of zebrafish during spawning season: ultrastructure and immunohistochemical profiles of Sox9 and Myostatin. Animals 13:3362. https://doi.org/10.3390/ani13213362\nMokhtar DM (2019) Characterization of fish ovarian stroma during spawning season: cytochemical, immunohistochemical and ultrastructural studies. Fish Shellfish Immunol 94:566–579. https://doi.org/10.1016/j.fsi.2019.09.050\nOngidi I, Abdulsalaam F, Otieno H et al (2020) A review of telocytes in cardiovascular tissue and their role in angiogenesis. Anat J Afr 9:1807–1815. https://doi.org/10.4314/aja.v9i2.199946\nPurelku M, Sahin H, Senturk GE, Tanriverdi G (2024) Distribution and morphologic characterization of telocytes in rat ovary and uterus: insights from ultrastructural and immunohistochemical analysis. Histochem Cell Biol 162:373–384. https://doi.org/10.1007/s00418-024-02313-w\nRosa I, Marini M, Guasti D et al (2018) Morphological evidence of telocytes in human synovium. Sci Rep 8:3581. https://doi.org/10.1038/s41598-018-22067-5\nRoss MH, Pawlina W (2019) Histology: a text and atlas. Morphologia 13:76–89. https://doi.org/10.26641/1997-9665.2019.4.76-89\nShafik A, Shafik AA, El Sibai O, Shafik IA (2005) Specialized pacemaking cells in the human Fallopian tube. Mol Hum Reprod 11:503–505. https://doi.org/10.1093/molehr/gah192\nSilva EG, Kim G, Bakkar R et al (2020) Histology of the normal ovary in premenopausal patients. Ann Diagn Pathol 46:151475. https://doi.org/10.1016/j.anndiagpath.2020.151475\nSuciu L, Popescu LM, Gherghiceanu M (2007) Human placenta: de visu demonstration of interstitial Cajal-like cells. J Cell Mol Med 11:590–597. https://doi.org/10.1111/j.1582-4934.2007.00058.x\nVannucchi MG, Faussone-Pellegrini MS (2016) The telocyte subtypes. Adv Exp Med Biol 913:115–126. https://doi.org/10.1007/978-981-10-1061-3_7\nVarga I, Urban L, Kajanová M, Polák Š (2016) Functional histology and possible clinical significance of recently discovered telocytes inside the female reproductive system. Arch Gynecol Obstet 294:417–422. https://doi.org/10.1007/s00404-016-4106-x\nWang X, Cretoiu D (2016) Telocytes: connecting cells. Adv Exp Med Biol 913:325–334\nZhang Y, Tian H (2023) Telocytes and inflammation: a review. Medicine 102:e35983. https://doi.org/10.1097/MD.0000000000035983\nZheng Y, Cretoiu D, Yan G et al (2014) Comparative proteomic analysis of human lung telocytes with fibroblasts. J Cell Mol Med 18:568–589. https://doi.org/10.1111/jcmm.12290\nAcknowledgements\nThis study was funded by the Istanbul University-Cerrahpasa Scientific Research Projects Unit, project no. 37035 and 36206.\nAuthor information\nAuthors and Affiliations\nContributions\nM.P. conducted all experiments, data analysis, and manuscript preparation. G.T. supervised and led the overall project. S.I. performed the pathological examination of the tissue samples. I.C., C.S., and S.S.C. assisted during the surgeries and provided the ovarian tissue samples. All authors reviewed and approved the final manuscript.\nCorresponding author\nEthics declarations\nConflict of interest\nThe authors declare no competing interests.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nPurelku, M., Cebi, C., Cebi, S. et al. First report of telocytes in human ovarian stroma: an ultrastructural and immunohistochemical study. Histochem Cell Biol 163, 119 (2025). https://doi.org/10.1007/s00418-025-02448-4\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s00418-025-02448-4","source_license":"CC0","license_restricted":false}