{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T21:04:16Z","timestamp":1785186256725,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T00:00:00Z","timestamp":1659225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Zinc (in the form of Zn2+) is necessary for male fertility. Both Zn2+ quantity and its localisation have been detected in seminal plasma and ejaculated spermatozoa, suggesting its active uptake via zinc import transporters (ZIPs). Immunofluorescence was used to characterise the expression and localisation of three distinct types of ZIP transporters in ejaculated spermatozoa of normo- and asthenozoospermic sperm samples. ZIP6, ZIP10 and ZIP14 showed heterogeneous sperm cell expression and different compartmental distribution. In both types of sperm samples, ZIP6 and ZIP14 were predominantly localised in the sperm head, while ZIP10 was found along the sperm tail. Compartmental localisation of ZIPs in asthenozoospermia was not changed. However, regarding sub-compartmental localisation in sperm head regions, for ZIP6 asthenozoospermia only decreased its acorn\/crescent-like pattern. In contrast, ZIP14 immunostaining was altered in favour of crescent-like, as opposed to acorn-like and acorn\/crescent-like patterns. The specific ZIPs localisation may reflect their different roles in sperm cell integrity and motility and may change over time. This is the first report of their specific compartmental and sub-compartmental localisation in ejaculated human sperm cells. Further research will lead to a greater understanding of the roles of ZIPs in sperm cell biology, which could positively influence procedures for human infertility therapy.<\/jats:p>","DOI":"10.3390\/cimb44080237","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T21:49:02Z","timestamp":1659304142000},"page":"3444-3454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Heterogeneous Immunolocalisation of Zinc Transporters ZIP6, ZIP10 and ZIP14 in Human Normo- and Asthenozoospermic Spermatozoa"],"prefix":"10.3390","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-2775","authenticated-orcid":false,"given":"Isidora","family":"Protic","sequence":"first","affiliation":[{"name":"Department of Medically Assisted Fertilisation of the Clinic for Gynecology and Obstetrics \u201cVisegradska\u201d, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5944-5053","authenticated-orcid":false,"given":"Igor","family":"Golic","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snezana","family":"Vidakovic","sequence":"additional","affiliation":[{"name":"Department of Medically Assisted Fertilisation of the Clinic for Gynecology and Obstetrics \u201cVisegradska\u201d, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5272-579X","authenticated-orcid":false,"given":"Bato","family":"Korac","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3044-9963","authenticated-orcid":false,"given":"Aleksandra","family":"Korac","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,31]]},"reference":[{"key":"ref_1","unstructured":"Collins, J.F. (2017). Chapter 23\u2014Zinc transporters in health and disease. Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals, Academic Press."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kerns, K., Zigo, M., and Sutovsky, P. (2018). Zinc: A necessary ion for mammalian sperm fertilization competency. Int. J. Mol. Sci., 19.","DOI":"10.20944\/preprints201811.0425.v1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1093\/clinchem\/29.4.629","article-title":"Identification of the serum binding proteins for iron, zinc, cadmium, nickel, and calcium","volume":"29","author":"Scott","year":"1983","journal-title":"Clin. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1093\/humrep\/deu075","article-title":"Role of zinc trafficking in male fertility: From germ to sperm","volume":"29","author":"Foresta","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vickram, S., Rohini, K., Srinivasan, S., Veenakumari, D.N., Archana, K., Anbarasu, K., Jeyanthi, P., Thanigaivel, S., Gulothungan, G., and Rajendiran, N. (2021). Role of zinc (Zn) in human reproduction: A journey from initial spermatogenesis to childbirth. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042188"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3945\/jn.110.131318","article-title":"Moderate zinc deficiency reduces testicular Zip6 and Zip10 abundance and impairs spermatogenesis in mice","volume":"141","author":"Croxford","year":"2011","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9156285","DOI":"10.1155\/2018\/9156285","article-title":"Critical role of zinc as either an antioxidant or a prooxidant in cellular systems","volume":"2018","author":"Lee","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_8","first-page":"69","article-title":"Zinc is an essential element for male fertility: A review of Zn roles in men\u2019s health, germination, sperm quality, and fertilization","volume":"19","author":"Fallah","year":"2018","journal-title":"J. Reprod. Infertil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/0024-3205(81)90374-X","article-title":"A critical physiological role of zinc in the structure and function of biomembranes","volume":"28","author":"Bettger","year":"1981","journal-title":"Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"155860","DOI":"10.1016\/j.scitotenv.2022.155860","article-title":"Environmental metal exposure, seminal plasma metabolome and semen quality: Evidence from Chinese reproductive-aged men","volume":"838","author":"Xu","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"824078","DOI":"10.3389\/fendo.2021.824078","article-title":"Systematic Review and Critical Analysis on Dietary Supplements for Male Infertility: From a Blend of Ingredients to a Rationale Strategy","volume":"12","author":"Garolla","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1152\/physrev.00035.2014","article-title":"The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism","volume":"95","author":"Kambe","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00018-003-3148-y","article-title":"Overview of mammalian zinc transporters","volume":"61","author":"Kambe","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12958-022-00893-7","article-title":"Zinc transporter ZIP12 maintains zinc homeostasis and protects spermatogonia from oxidative stress during spermatogenesis","volume":"20","author":"Zhu","year":"2022","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Atig, F., Raffa, M., Habib, B.A., Kerkeni, A., Saad, A., and Ajina, M. (2012). Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men. BMC Urol., 12.","DOI":"10.1186\/1471-2490-12-6"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1046\/j.1365-2605.1997.00060.x","article-title":"Histochemical demonstration of zinc ions in ejaculated human semen","volume":"20","author":"Stoltenberg","year":"1997","journal-title":"Int. J. Androl."},{"key":"ref_17","unstructured":"WHO (2022, April 11). Laboratory Manual for the Examination and Processing of Human Semen. Available online: https:\/\/www.who.int\/publications-detail-redirect\/9789240030787."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110800","DOI":"10.1016\/j.mehy.2022.110800","article-title":"Presence of acetylated \u03b1-tubulin in human sperm nuclei: A contributor to sperm heterogeneity","volume":"161","author":"Protic","year":"2022","journal-title":"Med. Hypotheses"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"767","DOI":"10.2298\/ABS150618061G","article-title":"Methods for studying the localization of mitochondrial complexes III and IV by immunofluorescent and immunogold microscopy","volume":"68","year":"2016","journal-title":"Arch. Biol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"58832","DOI":"10.18632\/oncotarget.11315","article-title":"Boar seminal plasma exosomes maintain sperm function by infiltrating into the sperm membrane","volume":"7","author":"Du","year":"2016","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.fertnstert.2019.01.030","article-title":"Seminal plasma of men with severe asthenozoospermia contain exosomes that affect spermatozoa motility and capacitation","volume":"111","author":"Murdica","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/BF01952862","article-title":"Zinc, copper and selenium in reproduction","volume":"50","author":"Bedwal","year":"1994","journal-title":"Experientia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1126\/scisignal.2001595","article-title":"Ca2+ signaling tools acquired from prostasomes are required for progesterone-induced sperm motility","volume":"4","author":"Park","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/and.12494","article-title":"Association between seminal plasma zinc level and asthenozoospermia: A meta-analysis study","volume":"48","author":"Taravati","year":"2016","journal-title":"Andrologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1748-1716.1985.tb07719.x","article-title":"Nuclear zinc in human epididymal and ejaculated spermatozoa","volume":"125","author":"Kvist","year":"1985","journal-title":"Acta Physiol. Scand."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1038\/s41467-018-04523-y","article-title":"Zinc ion flux during mammalian sperm capacitation","volume":"9","author":"Kerns","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/S0015-0282(99)00141-7","article-title":"Relevance of zinc in human sperm flagella and its relation to motility","volume":"71","author":"Henkel","year":"1999","journal-title":"Fertil. Steril."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1365-2605.1986.tb00869.x","article-title":"The human sperm nucleus takes up zinc at ejaculation","volume":"9","author":"Bjorndahl","year":"1986","journal-title":"Int. J. Androl."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1515\/reveh-2019-0008","article-title":"An overview on role of some trace elements in human reproductive health, sperm function and fertilization process","volume":"34","author":"Mirnamniha","year":"2019","journal-title":"Rev. Environ. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3109\/01485018808986737","article-title":"Human spermatozoal nuclear maturity in normozoospermia and asthenozoospermia","volume":"21","author":"Colleu","year":"1988","journal-title":"Arch. Androl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1439-0272.2010.01105.x","article-title":"Ejaculate fractions of asthenozoospermic and teratozoospermic patients have differences in the sperm DNA integrity","volume":"43","author":"Kumar","year":"2011","journal-title":"Andrologia"},{"key":"ref_32","first-page":"567","article-title":"The functional anatomy of the human spermatozoon: Relating ultrastructure and function","volume":"24","author":"Mortimer","year":"2018","journal-title":"Mol. Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1748-1716.1982.tb10598.x","article-title":"Importance of zinc for human sperm head-tail connection","volume":"116","author":"Kvist","year":"1982","journal-title":"Acta Physiol. Scand."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/44\/8\/237\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:27Z","timestamp":1760140827000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/44\/8\/237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,31]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["cimb44080237"],"URL":"https:\/\/doi.org\/10.3390\/cimb44080237","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,31]]}}}