{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T15:01:08Z","timestamp":1788188468618,"version":"build-2803163510"},"reference-count":143,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union through the European Regional Development Fund, under grant agreement","award":["No. KK.01.1.1.01.0008"],"award-info":[{"award-number":["No. KK.01.1.1.01.0008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mast cells (MCs) are an evolutionary well-conserved type of cells, mediating and modulating allergic responses in innate immunity and tissue remodeling after chronic inflammation. Among other tissues, they inhabit both the testis and epididymis. In the testis, MCs usually appear in the interstitial compartment in humans, but not in other standard experimental models, like rats and mice. MCs seem to be responsible for testicular tissue fibrosis in different causes of infertility. Although experimental animal models follow the effect on MC activation or penetration to the interstitial tissue like in humans to some extent, there is an inconsistency in the available literature regarding experimental design, animal strain, and detection methods used. This comprehensive review offers an insight into the literature on MCs in mammalian testes and epididymides. We aimed to find the most suitable model for research on MC and offer recommendations for future experimental designs. When using in vivo animal models, tunica albuginea incorporation and standard histological assessment need to be included. Domesticated boar strains kept in modified controlled conditions exhibit the highest similarity to the MC distribution in the human testis. 3D testicular models are promising but need further fine-tuning to become a valid model for MC investigation.<\/jats:p>","DOI":"10.3390\/ijms23052547","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:00:40Z","timestamp":1645783240000},"page":"2547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mast Cells in the Mammalian Testis and Epididymis\u2014Animal Models and Detection Methods"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2143-6968","authenticated-orcid":false,"given":"Marta","family":"Himelreich-Peri\u0107","sequence":"first","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Katu\u0161i\u0107-Bojanac","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Hoh\u0161teter","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2584-6654","authenticated-orcid":false,"given":"Nino","family":"Sin\u010di\u0107","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-1674","authenticated-orcid":false,"given":"Vedrana","family":"Mu\u017ei\u0107-Radovi\u0107","sequence":"additional","affiliation":[{"name":"Hospital for Medical Rehabilitation of the Health and Lung Diseases and Rheumatism \u201cThalassotherapia-Opatija\u201d, 51410 Opatija, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-5462","authenticated-orcid":false,"given":"Davor","family":"Je\u017eek","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Histology and Embryology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nature01324","article-title":"Mast cells in autoimmune disease","volume":"420","author":"Benoist","year":"2002","journal-title":"Nature"},{"key":"ref_2","unstructured":"Eurell, J.A.C., Frappier, B.L., and Dellmann, H.D. (2006). Dellmann\u2019s Textbook of Veterinary Histology; with CD, John Wiley & Sons."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhang, Z., and Kurashima, Y. (2021). Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute\/Chronic Inflammation. Cells, 10.","DOI":"10.3390\/cells10071615"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.immuni.2018.04.025","article-title":"Hemogenic Endothelial Fate Mapping Reveals Dual Developmental Origin of Mast Cells","volume":"48","author":"Gentek","year":"2018","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104273","DOI":"10.1016\/j.dci.2021.104273","article-title":"Analysis of the mast cell expressed carboxypeptidase A3 and its structural and evolutionary relationship to other vertebrate carboxypeptidases","volume":"127","author":"Akula","year":"2022","journal-title":"Dev. Comp. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1126\/science.271.5250.818","article-title":"Identification of a committed precursor for the mast cell lineage","volume":"271","author":"Rodewald","year":"1996","journal-title":"Science"},{"key":"ref_7","first-page":"321","article-title":"The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis","volume":"144","author":"Iemura","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.iac.2014.01.002","article-title":"Functional deregulation of KIT: Link to mast cell proliferative diseases and other neoplasms","volume":"34","author":"Cruse","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.46889\/JCMR.2021.2304","article-title":"c-Kit\u2014The Novel Receptor: Physiological Roles, Downstream Signaling and Implications in Cancer","volume":"2","author":"Vajravelu","year":"2021","journal-title":"J. Clin. Med. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1084\/jem.194.9.1243","article-title":"Intestinal mast cell progenitors require CD49dbeta7 (alpha4beta7 integrin) for tissue-specific homing","volume":"194","author":"Gurish","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_11","first-page":"33","article-title":"Mast cell and basophil development","volume":"1","author":"Galli","year":"1994","journal-title":"Curr. Opin. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000487538","article-title":"The Staining of Mast Cells: A Historical Overview","volume":"176","author":"Ribatti","year":"2018","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_13","unstructured":"Fong, M., and Crane, J.S. (2021). Histology, Mast Cells, StatPearls Publishing LLC."},{"key":"ref_14","first-page":"620","article-title":"Mast Cell: A Multi-Functional Master Cell","volume":"6","author":"Dileepan","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/jlb.63.3.337","article-title":"Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact","volume":"63","author":"Bhattacharyya","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1586\/eci.11.57","article-title":"The role of mast cells in male infertility","volume":"7","author":"Haidl","year":"2011","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.it.2012.09.008","article-title":"New models for analyzing mast cell functions in vivo","volume":"33","author":"Reber","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/jlb.61.3.233","article-title":"Development, significance, and heterogeneity of mast cells with particular regard to the mast cell-specific proteases chymase and tryptase","volume":"61","author":"Welle","year":"1997","journal-title":"J. Leukoc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/mi.2009.136","article-title":"Advances in mast cell biology: New understanding of heterogeneity and function","volume":"3","author":"Moon","year":"2010","journal-title":"Mucosal Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/all.13657","article-title":"Mast cell disorders: From infancy to maturity","volume":"74","author":"Wilcock","year":"2019","journal-title":"Allergy"},{"key":"ref_21","first-page":"e52753","article-title":"Analyzing the Functions of Mast Cells In Vivo Using \u2018Mast Cell Knock-in\u2019 Mice","volume":"99","author":"Gaudenzio","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Franke, K., Wang, Z., Zuberbier, T., and Babina, M. (2021). Cytokines Stimulated by IL-33 in Human Skin Mast Cells: Involvement of NF-\u03baB and p38 at Distinct Levels and Potent Co-Operation with Fc\u03b5RI and MRGPRX2. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073580"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nm.2755","article-title":"IgE and mast cells in allergic disease","volume":"18","author":"Galli","year":"2012","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nagata, K., and Nishiyama, C. (2021). IL-10 in Mast Cell-Mediated Immune Responses: Anti-Inflammatory and Proinflammatory Roles. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094972"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Quan, P.L., Sabat\u00e9-Bresc\u00f3, M., Gou, Y., Mart\u00edn, M., and Gastaminza, G. (2021). The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094421"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11628","DOI":"10.1038\/s41598-018-29965-8","article-title":"MRGPRX2-mediated mast cell response to drugs used inperioperative procedures and anaesthesia","volume":"8","author":"Lafuente","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.imlet.2020.07.006","article-title":"Baicalin induces Mrgprb2-dependent pseudo-allergy in mice","volume":"226","author":"Wang","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ogasawara, H., and Noguchi, M. (2021). Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells. Cells, 10.","DOI":"10.3390\/cells10112906"},{"key":"ref_29","first-page":"W2","article-title":"Mast cells in human foetal, cryptorchid and adult infertile testis","volume":"100","author":"Banek","year":"1998","journal-title":"Period Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0015-0282(00)00626-9","article-title":"Human testicular mast cells contain tryptase: Increased mast cell number and altered distribution in the testes of infertile men","volume":"74","author":"Meineke","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_31","first-page":"26","article-title":"The development and chronological changes of mast cell in testes of rats","volume":"7","author":"Zhou","year":"1998","journal-title":"Chin. J. Histochem. Cytochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/cmi.2014.38","article-title":"Testicular defense systems: Immune privilege and innate immunity","volume":"11","author":"Zhao","year":"2014","journal-title":"Cell. Mol. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13228","DOI":"10.1111\/aji.13228","article-title":"Significance of mast cells in spermatogenesis, implantation, pregnancy, and abortion: Cross talk and molecular mechanisms","volume":"83","author":"Shafaghat","year":"2020","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15072","DOI":"10.1073\/pnas.232422999","article-title":"Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPAR\u03b3: Possible relevance to human fibrotic disorders","volume":"99","author":"Frungieri","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/978-1-4939-1568-2_2","article-title":"The phylogenetic profile of mast cells","volume":"1220","author":"Crivellato","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.bbrc.2014.07.124","article-title":"Ancient origin of mast cells","volume":"451","author":"Wong","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.4067\/S0717-95022017000401359","article-title":"Morphology of the Interstitial Tissue of Active and Resting Testis of the Guinea Fowl","volume":"35","author":"Dharani","year":"2017","journal-title":"Int. J. Morphol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1159\/000143452","article-title":"The mast cells of Gallus domesticus","volume":"75","author":"Wight","year":"1970","journal-title":"Cells Tissues Organs"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/(SICI)1097-010X(19970601)278:2<93::AID-JEZ4>3.0.CO;2-#","article-title":"17\u03b2-estradiol effects on mast cell number and spermatogonial mitotic index in the testis of the frog, Rana esculenta","volume":"278","author":"Minucci","year":"1997","journal-title":"J. Exp. Zool."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1017\/S0967199400001027","article-title":"Effects of sex steroid hormones and their antagonists on mast cell number in the testis of the frog, Rana esculenta","volume":"8","author":"Matteo","year":"2000","journal-title":"Zygote"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1242\/jeb.00786","article-title":"Inhibition of the increased 17beta-estradiol-induced mast cell number by melatonin in the testis of the frog Rana esculenta, in vivo and in vitro","volume":"207","author":"Izzo","year":"2004","journal-title":"J. Exp. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-386037-8.00006-5","article-title":"Mast cells in nonmammalian vertebrates: An overview","volume":"290","author":"Baccari","year":"2011","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0940-9602(04)80009-8","article-title":"Morphology of the male reproductive duct system of Caiman crocodilus (Crocodylia, Alligatoridae)","volume":"186","author":"Guerrero","year":"2004","journal-title":"Ann. Anat.-Anat. Anz."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3109\/01485018608986939","article-title":"Increased number of mast cells in the testis of neonatally estrogenized rats","volume":"16","author":"Gaytan","year":"1986","journal-title":"Arch. Androl."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF00571426","article-title":"Differentiation of mast cells during postnatal development of neonatally estrogen-treated rats","volume":"259","author":"Gaytan","year":"1990","journal-title":"Cell Tissue Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1677\/joe.0.1460015","article-title":"Testicular serotonin is related to mast cells but not to Leydig cells in the rat","volume":"146","author":"Aguilar","year":"1995","journal-title":"J. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/path.1938","article-title":"Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2","volume":"208","author":"Iosub","year":"2006","journal-title":"J. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.urology.2003.08.010","article-title":"Protective effect of vasoactive intestinal peptide on testicular torsion-detorsion injury: Association with heparin-containing mast cells","volume":"63","author":"Can","year":"2004","journal-title":"Urology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/j.1600-0897.2010.00958.x","article-title":"Mast Cells and Ethanol Consumption: Interactions in the Prostate, Epididymis and Testis of UChB Rats","volume":"66","author":"Mendes","year":"2011","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_50","first-page":"111","article-title":"Toxic effect of acyclovir on testicular tissue in rats","volume":"11","author":"Movahed","year":"2013","journal-title":"Iran. J. Reprod. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/jemt.22664","article-title":"Ethanol exposure during peripubertal period increases the mast cell number and impairs meiotic and spermatic parameters in adult male rats","volume":"79","year":"2016","journal-title":"Microsc. Res. Tech."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF00233582","article-title":"Intertubular topography in the bovine testis","volume":"217","author":"Wrobel","year":"1981","journal-title":"Cell Tissue Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1095\/biolreprod51.3.551","article-title":"Leukocyte Populations of the Adult Rat Testis Following Removal of the Leydig Cells by Treatment With Ethane Dimethane Sulfonate and Subcutaneous Testosterone Implants","volume":"51","author":"Wang","year":"1994","journal-title":"Biol. Reprod."},{"key":"ref_54","first-page":"370","article-title":"Mast cell distribution in rats","volume":"44","author":"Majeed","year":"1994","journal-title":"Arzneimittelforschung"},{"key":"ref_55","first-page":"1170","article-title":"Mast cell distribution in mice","volume":"44","author":"Majeed","year":"1994","journal-title":"Arzneimittelforschung"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.114.120907","article-title":"Disruption of Rat Testis Development Following Combined In Utero Exposure to the Phytoestrogen Genistein and Antiandrogenic Plasticizer Di-(2-Ethylhexyl) Phthalate","volume":"91","author":"Jones","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.tice.2018.08.006","article-title":"Ameliorative effect of zinc oxide nanoparticles on cyclophosphamide induced testicular injury in adult rat","volume":"54","author":"Anan","year":"2018","journal-title":"Tissue Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1439-0442.1998.tb00819.x","article-title":"A comparative study of mast cells and eosinophil leukocytes in the mammalian testis","volume":"45","author":"Anton","year":"1998","journal-title":"Zentralbl Veterinarmed A"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1365-2222.1989.tb02357.x","article-title":"Mast cell heterogeneity","volume":"19","author":"Irani","year":"1989","journal-title":"Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1177\/8.1.18","article-title":"A correlative study of the histochemical properties of rodent acid mucopolysaccharides","volume":"8","author":"Spicer","year":"1960","journal-title":"J. Histochem. Cytochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/j.1939-4640.1992.tb03331.x","article-title":"Simultaneous Proliferation and Differentiation of Mast Cells and Leydig Cells in the Rat Testis","volume":"13","author":"Gaytan","year":"1992","journal-title":"J. Androl."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1159\/000234826","article-title":"Numbers and heterogeneity of mast cells in the male genital tract of the rat","volume":"88","author":"Fritz","year":"1989","journal-title":"Int. Arch. Allergy Appl. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1002\/1097-0142(19830315)51:6<1119::AID-CNCR2820510624>3.0.CO;2-M","article-title":"Benign and malignant mast cell proliferations. Diagnosis and separation using a pH-dependent toluidine blue stain in tissue section","volume":"51","author":"Klatt","year":"1983","journal-title":"Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1111\/j.1745-7262.2006.00146.x","article-title":"Immunohistopathology of the contralateral testis of rats undergoing experimental torsion of the spermatic cord","volume":"8","author":"Rodriguez","year":"2006","journal-title":"Asian J. Androl."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1095\/biolreprod35.2.425","article-title":"The Effects of Ethylene Dimethane Suiphonate (EDS) on Rat Leydig Cells: Evidence to Support a Connective Tissue Origin of Leydig Cells","volume":"35","author":"Jackson","year":"1986","journal-title":"Biol. Reprod."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-2605.1988.tb01024.x","article-title":"Assessment of the role of Leydig cell products other than testosterone in spermatogenesis and fertility in adult rats","volume":"11","author":"Sharpe","year":"1988","journal-title":"Int. J. Androl."},{"key":"ref_67","first-page":"1","article-title":"Testicular mast cells in autoimmune orchitis","volume":"33","author":"Lustig","year":"1995","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/jemt.23175","article-title":"Alcohol extract of Bauhinia forficata link reduces lipid peroxidation in the testis and epididymis of adult Wistar rats","volume":"82","author":"Sampaio","year":"2019","journal-title":"Microsc. Res. Tech."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1530\/jrf.0.0820381","article-title":"Abnormal development of the testis after administration of the Leydig cell cytotoxic ethylene-1,2-dimethanesulphonate to the immature rat","volume":"82","author":"Zaidi","year":"1988","journal-title":"J. Reprod. Fertil."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/j.1939-4640.1989.tb00117.x","article-title":"Mast cells in the testis, epididymis and accessory glands of the rat: Effects of neonatal steroid treatment","volume":"10","author":"Gaytan","year":"1989","journal-title":"J. Androl."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1530\/jrf.0.1020393","article-title":"Requirement for testicular macrophages in Leydig cell proliferation and differentiation during prepubertal development in rats","volume":"102","author":"Bellido","year":"1994","journal-title":"J. Reprod. Fertil."},{"key":"ref_72","first-page":"817","article-title":"The effect of vasoactive intestinal peptide (VIP) on mast cell invasion\/degranulation in testicular interstitium of immobilized + cold stressed and beta-endorphin-treated rats","volume":"17","author":"Aral","year":"1996","journal-title":"Peptides"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.2147\/DDDT.S67941","article-title":"The role of ketotifen in the prevention of testicular damage in rats with experimental unilateral undescended testes","volume":"8","author":"Acikgoz","year":"2014","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1134\/S1990519X16050060","article-title":"The influence of mast cells on reparative regeneration of tissues characterized by various degrees of immune privilege","volume":"10","author":"Khramtsova","year":"2016","journal-title":"Cell Tissue Biol."},{"key":"ref_75","first-page":"747","article-title":"Mast cell induction to the mouse testicular interstitium","volume":"85","author":"Qo","year":"1994","journal-title":"Nihon Hinyokika Gakkai Zasshi"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1210\/en.2005-0654","article-title":"Transgenic Mice Expressing P450 Aromatase as a Model for Male Infertility Associated with Chronic Inflammation in the Testis","volume":"147","author":"Li","year":"2006","journal-title":"Endocrinology"},{"key":"ref_77","unstructured":"Nour, N. (2016). Involvement of Activin and Follistatin in the Pathogenesis of Chronic Testicular Inflammation in Mice. [Ph.D. Thesis, Monash University]."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1038\/s41374-019-0299-5","article-title":"Retinoid-related orphan nuclear receptor alpha (ROR\u03b1)-deficient mice display morphological testicular defects","volume":"99","author":"Sayed","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_79","first-page":"2226","article-title":"Microanatomical Studies on the Testis of Domestic Pig (Sus scrofa domestica)","volume":"5","author":"Dhyana","year":"2016","journal-title":"Int. J. Sci. Environ. Tech."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00128-018-2377-6","article-title":"Dietary Exposure to Tebuconazole Affects Testicular and Epididymal Histomorphometry in Frugivorous Bats","volume":"101","author":"Neto","year":"2018","journal-title":"Bull Environ. Contam. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Souza, A.C.F., Santos, F.C., and Bastos, D.S.S. (2018). Reproductive functions in Desmodus rotundus: A comparison between seasons in a morphological context. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205023"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00441-017-2714-9","article-title":"Pattern of protein expression in the epididymis of Oligoryzomys nigripes (Cricetidae, Sigmodontinae)","volume":"372","author":"Menezes","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1159\/000054431","article-title":"Serotonin in Golden Hamster Testes: Testicular Levels, Immunolocalization and Role during Sexual Development and Photoperiodic Regression-Recrudescence Transition","volume":"69","author":"Frungieri","year":"1999","journal-title":"Neuroendocrinology"},{"key":"ref_84","first-page":"79","article-title":"Ethyl Pyruvate Ameliorates The Damage Induced by Cyclophosphamide on Adult Mice Testes","volume":"10","author":"Bakhtiary","year":"2016","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1530\/jrf.0.0570079","article-title":"Studies on the contractile activity and ultrastructure of the boar testicular capsule","volume":"57","author":"Ohanian","year":"1979","journal-title":"Reproduction"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1177\/0192623319827477","article-title":"Histological Changes of the Testicular Interstitium during Postnatal Development in Microminipigs","volume":"47","author":"Kangawa","year":"2019","journal-title":"Toxicol. Pathol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1054\/tice.2000.0145","article-title":"Cytology of the interstitial tissue in scrotal and abdominal testes of post-puberal boars","volume":"33","author":"Pinart","year":"2001","journal-title":"Tissue Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/aja.1001720205","article-title":"Morphology of the bovine epididymis","volume":"172","author":"Goyal","year":"1985","journal-title":"Am. J. Anat."},{"key":"ref_89","unstructured":"Abd-Elmaksoud, A. (2005). Morphological, Glycohistochemical, and Immunohistochemical Studies on the Embryonic and Adult Bovine Testis. [Ph.D. Thesis, LMU M\u00fcnchen, Faculty of Veterinary Medicine]."},{"key":"ref_90","unstructured":"Alkafafy, M. (2005). Glycohistochemical, Immunohistochemical and Ultrastructural Studies of the Bovine Epididymis. [Ph.D. Thesis, LMU M\u00fcnchen, Faculty of Veterinary Medicine]."},{"key":"ref_91","first-page":"8","article-title":"Postnatal development of the epididymis in the sheep","volume":"26","author":"Elzoghby","year":"2014","journal-title":"Benha Vet. Med. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1530\/jrf.0.1060017","article-title":"5-Hydroxytryptamine--a local regulator of testicular blood flow and vasomotion in rats","volume":"106","author":"Collin","year":"1996","journal-title":"J. Reprod. Fertil."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1083\/jcb.25.3.577","article-title":"Differentiation and proliferation of embryonic mast cells of the rat","volume":"25","author":"Combs","year":"1965","journal-title":"J. Cell Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1093\/humrep\/15.7.1543","article-title":"Significance of human testicular mast cells and their subtypes in male infertility","volume":"15","author":"Yamanaka","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.iac.2014.01.005","article-title":"Mastocytosis: Immunophenotypical features of the transformed mast cells are unique among hematopoietic cells","volume":"34","author":"Horny","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1369\/jhc.2009.953737","article-title":"Stage-specific localization and expression of c-kit in the adult human testis","volume":"57","author":"Unni","year":"2009","journal-title":"J. Histochem. Cytochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"136","DOI":"10.2164\/jandrol.106.000653","article-title":"Serotonin Concentration, Synthesis, Cell Origin, and Targets in the Rat Caput Epididymis During Sexual Maturation and Variations Associated With Adult Mating Status: Morphological and Biochemical Studies","volume":"28","year":"2007","journal-title":"J. Androl."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jim.2008.05.006","article-title":"High-affinity IgE receptor-beta chain expression in human mast cells","volume":"336","author":"Matsuda","year":"2008","journal-title":"J. Immunol. Methods"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1177\/104063879400600410","article-title":"Canine mast cell tumors: A comparison of staining techniques","volume":"6","author":"Simoes","year":"1994","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1189\/jlb.5RU0614-296R","article-title":"The immunophenotype of mast cells and its utility in the diagnostic work-up of systemic mastocytosis","volume":"97","author":"Teodosio","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Kritikou, E., Depuydt, M.A.C., de Vries, M.R., Mulder, K.E., Govaert, A.M., Smit, M.D., van Duijn, J., Foks, A.C., Wezel, A., and Smeets, H.J. (2019). Flow Cytometry-Based Characterization of Mast Cells in Human Atherosclerosis. Cells, 8.","DOI":"10.3390\/cells8040334"},{"key":"ref_102","unstructured":"(2021, January 15). Digital_Histology. Available online: https:\/\/digitalhistology.org\/organs-systems\/reproductive\/male\/testis\/testis-proper\/testis-proper-1\/."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1210\/endo-125-4-2212","article-title":"Histamine affects testicular steroid production in the golden hamster","volume":"125","author":"Mayerhofer","year":"1989","journal-title":"Endocrinology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000054519","article-title":"Neuronal Elements in the Testis of the Rhesus Monkey: Ontogeny, Characterization and Relationship to Testicular Cells","volume":"71","author":"Frungieri","year":"2000","journal-title":"Neuroendocrinology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/molehr\/gay025","article-title":"Characterization of a non-human primate model for the study of testicular peritubular cells-comparison with human testicular peritubular cells","volume":"24","author":"Schmid","year":"2018","journal-title":"Mol. Hum. Reprod."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.fertnstert.2004.11.062","article-title":"Phenotypic characterization of the immune and mast cell infiltrates in the human testis shows normal and abnormal spermatogenesis","volume":"83","author":"Hussein","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1080\/01485010290099183","article-title":"Mast Cells and Fibrosis on Testicular Biopsies in Male Infertility","volume":"48","author":"Apa","year":"2002","journal-title":"Arch. Androl."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1046\/j.1439-0272.1999.00287.x","article-title":"Mast cells in testicular biopsies of infertile men with \u2018mixed atrophy\u2019 of seminiferous tubules","volume":"31","author":"Jezek","year":"1999","journal-title":"Andrologia"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1002\/cncr.22662","article-title":"Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia","volume":"109","author":"Shanafelt","year":"2007","journal-title":"Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Mulvihill, J.J., and Garlow, T.J. (2007). Reproductive Outcomes among Men Treated for Cancer. Male-Mediated Developmental Toxicity, The Royal Society of Chemistry. Chapter 2.","DOI":"10.1039\/9781847557643-00005"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/291159a0","article-title":"Spleen colony-forming cell as common precursor for tissue mast cells and granulocytes","volume":"291","author":"Kitamura","year":"1981","journal-title":"Nature"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2131\/jts.33.61","article-title":"A purine nucleoside analogue-acyclovir [9-(2-hydroxyethoxymethyl)-9h-guanine] reversibly impairs testicular functions in mouse","volume":"33","author":"Narayana","year":"2008","journal-title":"J. Toxicol. Sci."},{"key":"ref_113","first-page":"518","article-title":"Evaluation of Oral Acyclovir Therapy","volume":"19","author":"Fletcher","year":"1985","journal-title":"Drug Intell. Clin. Pharm."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/0024-3205(87)90037-3","article-title":"Species differences in metabolism of ketotifen in rat, rabbit and man: Demonstration of similar pathways in vivo and in cultured hepatocytes","volume":"40","author":"Begue","year":"1987","journal-title":"Life Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/j.1439-0272.1986.tb01831.x","article-title":"The use of ketotifen, a mast cell blocker, for treatment of oligo- and asthenozoospermia","volume":"18","author":"Schill","year":"1986","journal-title":"Andrologia"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.fertnstert.2005.06.047","article-title":"Ketotifen improves sperm motility and sperm morphology in male patients with leukocytospermia and unexplained infertility","volume":"85","author":"Oliva","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1365-2605.2010.01112.x","article-title":"Zaditen (Ketotifen), as mast cell blocker, improves sperm quality, chromatin integrity and pregnancy rate after varicocelectomy","volume":"34","author":"Azadi","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4103\/aja.aja_30_19","article-title":"Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord","volume":"22","author":"Moreno","year":"2020","journal-title":"Asian J. Androl."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Iosub, I.R. (2006). Pathomechanism of Testicular Inflammation in Rat Involves Activation of Proteinase Activated Receptor 2. [Ph.D. Thesis, University Of Giessen].","DOI":"10.1002\/path.1938"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.2047-2927.2014.00227.x","article-title":"Are testicular mast cells involved in the regulation of germ cells in man?","volume":"2","author":"Nettersheim","year":"2014","journal-title":"Andrology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"291.e1","DOI":"10.1016\/j.jpurol.2021.01.045","article-title":"The effect of hypothermia in a rat testicular torsion\/detorsion model","volume":"17","author":"Yenisey","year":"2021","journal-title":"J. Pediatr. Urol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1002\/j.1460-2075.1990.tb08305.x","article-title":"Molecular bases of dominant negative and loss of function mutations at the murine c-kit\/white spotting locus: W37, Wv, W41 and W","volume":"9","author":"Nocka","year":"1990","journal-title":"EMBO J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"31515","DOI":"10.1038\/srep31515","article-title":"Disruption of c-Kit Signaling in KitW-sh\/W-sh Growing Mice Increases Bone Turnover","volume":"6","author":"Lotinun","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1677\/joe.0.1530337","article-title":"Stem cell factor and c-kit in the mammalian testis: Lessons originating from Mother Nature\u2019s gene knockouts","volume":"153","author":"Loveland","year":"1997","journal-title":"J. Endocrinol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.3389\/fimmu.2019.02399","article-title":"Chymase-Cre; Mcl-1fl\/fl Mice Exhibit Reduced Numbers of Mucosal Mast Cells","volume":"10","author":"Luo","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_126","first-page":"901","article-title":"Comparison of testis structure, function and thyroid hormone levels in control C57BL\/6 mice and anti-mullerian hormone over expressing mice","volume":"25","author":"Ariyaratne","year":"2010","journal-title":"Histol. Histopathol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jpurol.2013.11.014","article-title":"A Mast cell numbers negatively correlate with fibrosis in cryptorchid testes","volume":"10","author":"Mechlin","year":"2014","journal-title":"J. Pediatr. Urol."},{"key":"ref_128","first-page":"7","article-title":"Investigation of Testicular Mast Cells and Fibrosis in Rats With Experimental Unilateral Cryptorchidism","volume":"11","author":"Duran","year":"2021","journal-title":"Bozok T\u0131p Dergisi"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1128\/iai.60.6.2324-2328.1992","article-title":"Experimental epididymitis due to Chlamydia trachomatis in rats","volume":"60","author":"Jantos","year":"1992","journal-title":"Infect. Immun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/030098588402100216","article-title":"Pathogenesis of Trypanosoma brucei infection in deer mice (Peromyscus maniculatus). Ultrastructural pathology of the spleen, liver, heart, and kidney","volume":"21","author":"Anosa","year":"1984","journal-title":"Vet. Pathol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1600-065X.2006.00438.x","article-title":"The testis in immune privilege","volume":"213","author":"Fijak","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_132","first-page":"159","article-title":"Emergent roles for intercellular adhesion molecule-1 in the restructuring of the blood-testis barrier during spermatogenesis in the mammal","volume":"31","author":"Mruk","year":"2016","journal-title":"Histol. Histopathol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1530\/REP-15-0463","article-title":"Regulation of blood-testis barrier by actin binding proteins and protein kinases","volume":"151","author":"Li","year":"2016","journal-title":"Reproduction"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1210\/er.2014-1101","article-title":"The Mammalian Blood-Testis Barrier: Its Biology and Regulation","volume":"36","author":"Mruk","year":"2015","journal-title":"Endocr. Rev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e13055","DOI":"10.1111\/and.13055","article-title":"Human testicular peritubular cells, mast cells and testicular inflammation","volume":"50","author":"Mayerhofer","year":"2018","journal-title":"Andrologia"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.anireprosci.2014.06.008","article-title":"Influences on semen traits used for selection of young AI boars","volume":"148","author":"Schulze","year":"2014","journal-title":"Anim. Reprod. Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.theriogenology.2004.01.003","article-title":"Semen quality of postpubertal boars during increasing and decreasing natural photoperiods","volume":"62","author":"Sancho","year":"2004","journal-title":"Theriogenology"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.anireprosci.2003.08.006","article-title":"The effect of season on the properties of wild boar (Sus scrofa L.) semen","volume":"80","author":"Kozdrowski","year":"2004","journal-title":"Anim Reprod Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/imr.12636","article-title":"Is it time for a new classification of mast cells? What do we know about mast cell heterogeneity?","volume":"282","author":"Frossi","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.4049\/jimmunol.137.6.2009","article-title":"Mast cell \u201cdisappearance\u201d in chronic murine graft-vs-host disease (GVHD)-ultrastructural demonstration of \u201cphantom mast cells\u201d","volume":"137","author":"Claman","year":"1986","journal-title":"J. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-1-0716-0696-4_22","article-title":"Detection of Mast Cells and Basophils by Immunohistochemistry","volume":"2163","author":"Walls","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/andr.12710","article-title":"Rebuilding the human testis in vitro","volume":"8","author":"Oliver","year":"2020","journal-title":"Andrology"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"bqab033","DOI":"10.1210\/endocr\/bqab033","article-title":"Regulation of Cell Types Within Testicular Organoids","volume":"162","author":"Lara","year":"2021","journal-title":"Endocrinology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/5\/2547\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:27:33Z","timestamp":1760135253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/5\/2547"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":143,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23052547"],"URL":"https:\/\/doi.org\/10.3390\/ijms23052547","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]}}}