{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:17:46Z","timestamp":1790957866413,"version":"4.1.0"},"reference-count":146,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zinc (Zn), the second-most necessary trace element, is abundant in the human body. The human body lacks the capacity to store Zn; hence, the dietary intake of Zn is essential for various functions and metabolism. The uptake of Zn during its transport through the body is important for proper development of the three major accessory sex glands: the testis, epididymis, and prostate. It plays key roles in the initial stages of germ cell development and spermatogenesis, sperm cell development and maturation, ejaculation, liquefaction, the binding of spermatozoa and prostasomes, capacitation, and fertilization. The prostate releases more Zn into the seminal plasma during ejaculation, and it plays a significant role in sperm release and motility. During the maternal, labor, perinatal, and neonatal periods, the part of Zn is vital. The average dietary intake of Zn is in the range of 8\u201312 mg\/day in developing countries during the maternal period. Globally, the dietary intake of Zn varies for pregnant and lactating mothers, but the average Zn intake is in the range of 9.6\u201311.2 mg\/day. The absence of Zn and the consequences of this have been discussed using critical evidence. The events and functions of Zn related to successful fertilization have been summarized in detail. Briefly, our current review emphasizes the role of Zn at each stage of human reproduction, from the spermatogenesis process to childbirth. The role of Zn and its supplementation in in vitro fertilization (IVF) opens opportunities for future studies on reproductive biology.<\/jats:p>","DOI":"10.3390\/ijms22042188","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T14:23:27Z","timestamp":1614003807000},"page":"2188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Role of Zinc (Zn) in Human Reproduction: A Journey from Initial Spermatogenesis to Childbirth"],"prefix":"10.3390","volume":"22","author":[{"given":"Sundaram","family":"Vickram","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-192X","authenticated-orcid":false,"given":"Karunakaran","family":"Rohini","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Faculty of Medicine, AIMST University, Semeling, Bedong 08100, Kedah, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramanian","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Nancy Veenakumari","sequence":"additional","affiliation":[{"name":"BCX Bioorganics, Krishnasagara Village, Attibele, Bengaluru, Karnataka 562107, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar","family":"Archana","sequence":"additional","affiliation":[{"name":"Department of Agriculture Engineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan","family":"Anbarasu","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palanivelu","family":"Jeyanthi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Vel Tech Rangarajan Dr. Sagunthala R&amp;D Institute of Science and Technology, Chennai, Tamil Nadu 600062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundaram","family":"Thanigaivel","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Govindarajan","family":"Gulothungan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanmaran","family":"Rajendiran","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmalayam Sadanandan","family":"Srikumar","sequence":"additional","affiliation":[{"name":"Unit of Psychiatry, Faculty of Medicine, AIMST University, Semeling, Bedong 08100, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"ref_1","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_2","first-page":"133","article-title":"Zinc and iron in soil, plant, animal and human health","volume":"12","author":"Shukla","year":"2016","journal-title":"Indian J. Fertil."},{"key":"ref_3","unstructured":"Prasad, A.S. (2017). Trace metals in growth and sexual maturation. Metabolism of Trace Metals in Man Volume I (1984): Developmental Aspects, CRC Press."},{"key":"ref_4","unstructured":"World Health Organization (2019). Global Status Report on Alcohol and Health 2018, World Health Organization."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jtemb.2018.08.005","article-title":"Trace elements content in semen and their interactions with sperm quality and RedOx status in freshwater fish Cyprinus carpio: A correlation study","volume":"50","author":"Kovacik","year":"2018","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","unstructured":"Wessels, I., Maywald, M., and Rink, L. (2017). Zinc as a gatekeeper of immune function. Nutrients, 9.","DOI":"10.3390\/nu9121286"},{"key":"ref_8","first-page":"204","article-title":"The association between dietary antioxidant intake and semen quality in infertile men","volume":"27","author":"Nadjarzadeh","year":"2013","journal-title":"Med. J. Islamic Repub. Iran"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/aps.2018.25","article-title":"Zinc deficiency and cellular oxidative stress: Prognostic implications in cardiovascular diseases","volume":"39","author":"Choi","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.semcdb.2014.02.011","article-title":"Sertoli cells\u2013immunological sentinels of spermatogenesis","volume":"30","author":"Kaur","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_11","first-page":"231","article-title":"The role of zinc in the endocrine system","volume":"32","author":"Baltaci","year":"2019","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1017\/S0967199417000028","article-title":"Impaired hypothalamic-pituitary-testicular axis activity, spermatogenesis, and sperm function promote infertility in males with lead poisoning","volume":"25","author":"Gandhi","year":"2017","journal-title":"Zygote"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3945\/an.112.003210","article-title":"Discovery of human zinc deficiency: Its impact on human health and disease","volume":"4","author":"Prasad","year":"2013","journal-title":"Adv. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12958-018-0358-6","article-title":"The enigmatic seminal plasma: A proteomics insight from ejaculation to fertilization","volume":"16","author":"Samanta","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_15","unstructured":"Brazdova, A. (2014). Study of Immunological Properties of Sperm and Seminal Plasma Antigens: Anti-Seminal and Anti-Sperm Antibodies in Female Immune Infertility: Characterization of Targeted Proteins. [Doctoral dissertation, Universite Pierre et Marie Curie-Paris VI]."},{"key":"ref_16","first-page":"17","article-title":"Effects of zinc on male sex hormones and semen quality in rats","volume":"28","author":"Egwurugwu","year":"2013","journal-title":"Niger. J. Physiol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10534-013-9618-2","article-title":"Zinc-rich inhibitor of apoptosis proteins (IAPs) as regulatory factors in the epithelium of normal and inflamed airways","volume":"26","author":"Roscioli","year":"2013","journal-title":"Biometals"},{"key":"ref_18","first-page":"52","article-title":"The key role of zinc in enhancement of total antioxidant levels in spermatozoa of patients with asthenozoospermia","volume":"1","author":"Hadwan","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_19","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_20","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_21","first-page":"577","article-title":"Zinc therapy improves adverse effects of long term administration of copper on epididymal sperm quality of rats","volume":"11","author":"Babaei","year":"2013","journal-title":"Iran. J. Reprod. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1007\/s00018-014-1617-0","article-title":"Current understanding of ZIP and ZnT zinc transporters in human health and diseases","volume":"71","author":"Kambe","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10815-012-9926-4","article-title":"Prediction of Zn concentration in human seminal plasma of Normospermia samples by Artificial Neural Networks (ANN)","volume":"30","author":"Vickram","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_24","first-page":"1","article-title":"Zinc ion flux during mammalian sperm capacitation","volume":"9","author":"Kerns","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1093\/molehr\/gau066","article-title":"Maternally-derived zinc transporters ZIP6 and ZIP10 drive the mammalian oocyte-to-egg transition","volume":"20","author":"Kong","year":"2014","journal-title":"Mol. Hum. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.semcdb.2014.04.005","article-title":"The regulation of spermatogenesis and sperm function in nematodes","volume":"29","author":"Ellis","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3109\/15376516.2012.731437","article-title":"Effects of Zn deficiency, antioxidants, and low-dose radiation on diabetic oxidative damage and cell death in the testis","volume":"23","author":"Zhao","year":"2013","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.semcdb.2014.04.007","article-title":"The roles and regulation of Sertoli cells in fate determinations of spermatogonial stem cells and spermatogenesis","volume":"29","author":"Hai","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bradbury, N.A. (2017). All cells have a sex: Studies of sex chromosome function at the cellular level. Principles of Gender-Specific Medicine, Academic Press.","DOI":"10.1016\/B978-0-12-803506-1.00051-6"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1093\/humrep\/dey283","article-title":"Decrease in semen quality and Leydig cell function in infertile men: A longitudinal study","volume":"33","author":"Olesen","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4103\/0970-1591.139570","article-title":"Molecular basis for the effects of zinc deficiency on spermatogenesis: An experimental study in the Sprague-dawley rat model","volume":"31","author":"Omu","year":"2015","journal-title":"Indian J. Urol. IJU: J. Urol. Soc. India"},{"key":"ref_32","first-page":"60","article-title":"The role of oxidative stress and antioxidants in male fertility","volume":"66","author":"Wolski","year":"2013","journal-title":"Cent. Eur. J. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bolanca, I., Obhodas, J., Ljiljak, D., Matjacic, L., and Kuna, K. (2016). Synergetic effects of K, Ca, Cu and Zn in human semen in relation to parameters indicative of spontaneous hyperactivation of spermatozoa. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152445"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/dgd.12301","article-title":"Abnormal spermatogenesis and male infertility in testicular zinc finger protein Zfp318-knockout mice","volume":"58","author":"Ishizuka","year":"2016","journal-title":"Dev. Growth Differ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1242\/dev.132605","article-title":"KRAB zinc finger proteins","volume":"144","author":"Ecco","year":"2017","journal-title":"Development"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s13273-015-0040-4","article-title":"Transcriptional regulation of KRAB-ZFPs in cancer","volume":"11","author":"Lim","year":"2015","journal-title":"Mol. Cell. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/14647273.2018.1494390","article-title":"Effects of zinc deficiency on impaired spermatogenesis and male infertility: The role of oxidative stress, inflammation and apoptosis","volume":"23","author":"Harchegani","year":"2020","journal-title":"Hum. Fertil."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ygcen.2017.04.016","article-title":"ZIP9, a novel membrane androgen receptor and zinc transporter protein","volume":"257","author":"Thomas","year":"2018","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Karweina, D., Kreuzer-Redmer, S., M\u00fcller, U., Franken, T., Pieper, R., Baron, U., Olek, S., Zentek, J., and Brockmann, G.A. (2015). The zinc concentration in the diet and the length of the feeding period affect the methylation status of the ZIP4 zinc transporter gene in piglets. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143098"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1177\/0748233716637543","article-title":"The protective effects of zinc in lead-induced testicular and epididymal toxicity in Wistar rats","volume":"33","author":"Anjum","year":"2017","journal-title":"Toxicol. Ind. Health"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.reprotox.2016.06.005","article-title":"Protective role of zinc against the toxicity induced by exposure to cadmium during gestation and lactation on testis development","volume":"63","author":"Chemek","year":"2016","journal-title":"Reprod. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"403","DOI":"10.29252\/ijrm.15.7.403","article-title":"Combined protective effect of zinc oxide nanoparticles and melatonin on cyclophosphamide-induced toxicity in testicular histology and sperm parameters in adult Wistar rats","volume":"15","author":"Torabi","year":"2017","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_43","first-page":"151","article-title":"Bone benefits of testosterone replacement therapy in male hypogonadism","volume":"56","author":"Tirabassi","year":"2014","journal-title":"Panminerva Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.ecoenv.2015.09.011","article-title":"Zinc\u2013cadmium interactions: Impact on wheat physiology and mineral acquisition","volume":"122","author":"Sarwar","year":"2015","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_45","unstructured":"Bayer, A.R. (2018). Zinc Dynamics during Murine Gamete and Embryo Development. [Ph.D. Thesis, Northwestern University]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"984","DOI":"10.2527\/jas.2013-6843","article-title":"Cryopreservation of porcine spermatogonial stem cells by slow-freezing testis tissue in trehalose","volume":"92","author":"Lee","year":"2014","journal-title":"J. Anim. Sci."},{"key":"ref_47","first-page":"E5464","article-title":"Zinc-sensitive MRI contrast agent detects differential release of Zn (II) ions from the healthy vs. malignant mouse prostate","volume":"113","author":"Jordan","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2174\/1573399810666140606111745","article-title":"Diabetes mellitus induced impairment of male reproductive functions: A review","volume":"10","year":"2014","journal-title":"Curr. Diabetes Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nrurol.2017.69","article-title":"Oxidative stress and male infertility","volume":"14","author":"Bisht","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_50","first-page":"415","article-title":"Toxicology of cadmium and its damage to mammalian organs","volume":"Volume 11","author":"Lee","year":"2013","journal-title":"Cadmium: From Toxicity to Essentiality"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrurol.2016.89","article-title":"The role of the prostate in male fertility, health and disease","volume":"13","author":"Verze","year":"2016","journal-title":"Nat. Rev. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4103\/2277-8632.158577","article-title":"A review on role of essential trace elements in health and disease","volume":"4","author":"Prashanth","year":"2015","journal-title":"J. Dr. NTR Univ. Health Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.rbmo.2014.02.013","article-title":"Proteomics, oxidative stress and male infertility","volume":"29","author":"Agarwal","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1093\/jnci\/95.13.1004","article-title":"Zinc supplement use and risk of prostate cancer","volume":"95","author":"Leitzmann","year":"2003","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1089\/vim.2013.0136","article-title":"Role of semen in altering the balance between inflammation and tolerance in the female genital tract: Does it contribute to HIV risk?","volume":"27","author":"Rametse","year":"2014","journal-title":"Viral Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1080\/09603123.2014.958137","article-title":"Role of low exposure to metals as male reproductive toxicants","volume":"25","author":"Jeng","year":"2015","journal-title":"Int. J. Environ. Health Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.mam.2012.11.007","article-title":"Zinc transporters in prostate cancer","volume":"34","author":"Franz","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1039\/C4MT00108G","article-title":"ZnT-1 extrudes zinc from mammalian cells functioning as a Zn2+ \/H+ exchanger","volume":"6","author":"Shusterman","year":"2014","journal-title":"Metallomics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/rda.12541","article-title":"Signalling events and associated pathways related to the mammalian sperm capacitation","volume":"50","author":"Gangwar","year":"2015","journal-title":"Reprod. Domest. Anim."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.cbpc.2016.09.007","article-title":"Zinc availability during germline development impacts embryo viability in Caenorhabditis elegans","volume":"191","author":"Mendoza","year":"2017","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1089\/ars.2013.5806","article-title":"Voltage-gated proton channels as novel drug targets: From NADPH oxidase regulation to sperm biology","volume":"23","author":"Seredenina","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_62","first-page":"1","article-title":"Focal adhesion kinases and calcium\/calmodulin-dependent protein kinases regulate protein tyrosine phosphorylation in stallion sperm","volume":"88","author":"Loux","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pneurobio.2013.10.003","article-title":"Role of the ubiquitin\u2013proteasome system in brain ischemia: Friend or foe?","volume":"112","author":"Caldeira","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.2047-2927.2012.00025.x","article-title":"Seminal vesicles and diabetic neuropathy: Ultrasound evaluation after prolonged treatment with a selective phosphodiesterase-5 inhibitor","volume":"1","author":"Condorelli","year":"2013","journal-title":"Andrology"},{"key":"ref_65","first-page":"7594","article-title":"Calcification of the vas deferens and seminal vesicles: A review","volume":"22","author":"Stasinou","year":"2015","journal-title":"Can. J. Urol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/ca.22655","article-title":"Comprehensive review of the anatomy and physiology of male ejaculation: Premature ejaculation is not a disease","volume":"29","author":"Puppo","year":"2016","journal-title":"Clin. Anat."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7221","DOI":"10.1128\/JVI.00269-14","article-title":"Liquefaction of semen generates and later degrades a conserved semenogelin peptide that enhances HIV infection","volume":"88","author":"Roan","year":"2014","journal-title":"J. Virol."},{"key":"ref_68","first-page":"224","article-title":"Semen hyperviscosity: Causes, consequences, and cures","volume":"5","author":"Gokul","year":"2013","journal-title":"Front. Biosci."},{"key":"ref_69","unstructured":"Silverberg, K.M., and Turner, T. (2017). Evaluation of sperm. Textbook of Assisted Reproductive Techniques: Volume 1: Laboratory Perspectives, CRC Press."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2167-0501.1000141","article-title":"Sodium, potassium, calcium and copper levels in seminal plasma are associated with sperm quality in fertile and infertile men","volume":"3","author":"Hamad","year":"2014","journal-title":"Biochem Pharm."},{"key":"ref_71","unstructured":"Boshoff, N.H. (2014). The Influence of Genotype on Sperm Motility and Sperm Head Morphometry of Merino (Ovis aries) Sheep. [Ph.D. Thesis, Stellenbosch University]."},{"key":"ref_72","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dungan, K., Grossman, A., Hershman, J.M., Hofland, J., and Kaltsas, G. (2021, February 20). Clinical Management of Male Infertility, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK279160\/."},{"key":"ref_73","unstructured":"Marques, P.I.F. (2016). An Evolutionary Perspective into the Role Of Kallikreins (KLKs) in Male Reproductive Biology, Universidade do Porto (Portugal), ProQuest Dissertations Publishing."},{"key":"ref_74","first-page":"507","article-title":"Potential for sexual conflict assessed via testosterone-mediated transcriptional changes in liver and muscle of a songbird","volume":"217","author":"Peterson","year":"2014","journal-title":"J. Exp. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/humupd\/dmv008","article-title":"Morphological and functional maturation of Leydig cells: From rodent models to primates","volume":"21","author":"Teerds","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.3892\/ijmm.2016.2576","article-title":"A potential role for zinc transporter 7 in testosterone synthesis in mouse Leydig tumor cells","volume":"37","author":"Chu","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.13005\/bpj\/1342","article-title":"Thyroid disorders and semen quality","volume":"11","author":"Sengupta","year":"2018","journal-title":"Biomed. Pharmacol. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.bbrc.2014.02.055","article-title":"Zinc protects cyclophosphamide-induced testicular damage in rat: Involvement of metallothionein, tesmin and Nrf2","volume":"445","author":"Maremanda","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_79","first-page":"99","article-title":"Inflammation and Ageing: Probable role in Male infertility","volume":"7","author":"Acharyya","year":"2020","journal-title":"Chem. Biol. Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2174\/18746098112059990008","article-title":"Testosterone deficiency syndrome: Cellular and molecular mechanism of action","volume":"6","author":"Carruthers","year":"2013","journal-title":"Curr. Aging Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nrurol.2014.74","article-title":"Seminal plasma as a diagnostic fluid for male reproductive system disorders","volume":"11","author":"Drabovich","year":"2014","journal-title":"Nat. Rev. Urol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/REP-13-0358","article-title":"Prostasomes: Extracellular vesicles from the prostate","volume":"147","author":"Aalberts","year":"2014","journal-title":"Reproduction"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1016\/j.bbapap.2012.08.008","article-title":"Spermatozoa recruit prostasomes in response to capacitation induction","volume":"1834","author":"Aalberts","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA) Proteins Proteom."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.ijbiomac.2019.09.218","article-title":"Human prostasomes an extracellular vesicle\u2013Biomarkers for male infertility and prostrate cancer: The journey from identification to current knowledge","volume":"146","author":"Vickram","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"18757","DOI":"10.1074\/jbc.M115.640524","article-title":"Characterization of Zinc Influx Transporters (ZIPs) in Pancreatic \u03b2 Cells Roles in Regulating Cytosolic Zinc Homeostasis and Insulin Secretion","volume":"290","author":"Liu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1093\/humrep\/det039","article-title":"Spermatogonial stem cell preservation and transplantation: From research to clinic","volume":"28","author":"Goossens","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_87","first-page":"IE01","article-title":"The impact of oxidative stress on testicular function and the role of antioxidants in improving it: A review","volume":"11","author":"Asadi","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1517\/14728222.2013.733001","article-title":"Targeting the Bcl-2 family for cancer therapy","volume":"17","author":"Thomas","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cellsig.2012.12.013","article-title":"Zinc transporter 5 and zinc transporter 7 induced by high glucose protects peritoneal mesothelial cells from undergoing apoptosis","volume":"25","author":"Zhang","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00204-014-1448-7","article-title":"The mystery of BCL2 family: Bcl-2 proteins and apoptosis: An update","volume":"89","author":"Siddiqui","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_91","first-page":"2","article-title":"Human sperm DNA fragmentation and its correlation with conventional semen parameters","volume":"15","author":"Evgeni","year":"2014","journal-title":"J. Reprod. Infertil."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12958-018-0406-2","article-title":"Reactive oxygen species and male reproductive hormones","volume":"16","author":"Darbandi","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/iwj.12557","article-title":"Reactive oxygen species (ROS) and wound healing: The functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process","volume":"14","author":"Dunnill","year":"2017","journal-title":"Int. Wound J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fnagi.2014.00077","article-title":"The role of intracellular zinc release in aging, oxidative stress, and Alzheimer\u2019s disease","volume":"6","author":"McCord","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jtherbio.2017.01.002","article-title":"Preventive effects of supplemental dietary zinc on heat-induced damage in the epididymis of boars","volume":"64","author":"Li","year":"2017","journal-title":"J. Therm. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5534\/wjmh.2014.32.1.1","article-title":"Effect of oxidative stress on male reproduction","volume":"32","author":"Agarwal","year":"2014","journal-title":"World J. Men\u2019s Health"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.lfs.2015.02.027","article-title":"Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure","volume":"130","author":"Kirsten","year":"2015","journal-title":"Life Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s11357-011-9347-9","article-title":"Chronic hyponatremia exacerbates multiple manifestations of senescence in male rats","volume":"35","author":"Barsony","year":"2013","journal-title":"Age"},{"key":"ref_99","unstructured":"Garcia Barros, R., Franciosi, F., Dall Acqua, P., Dieci, C., Lodde, V., and Luciano, A. Zinc supplementation during in vitro culture of bovine growing oocytes. Proceedings of the Technologies and controversies in reproduction. International conference proceedings, Available online: https:\/\/fertilityconference.org\/wp-content\/uploads\/2018\/12\/Fertility_2019_abstracts_book-updated."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"6762343","DOI":"10.1155\/2016\/6762343","article-title":"Roles of zinc signaling in the immune system","volume":"2016","author":"Hojyo","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_101","unstructured":"Prasad, A.S. (2013). Biochemistry of Zinc, Springer Science & Business Media."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.devcel.2013.03.001","article-title":"Fetuin-B, a liver-derived plasma protein is essential for fertilization","volume":"25","author":"Dietzel","year":"2013","journal-title":"Dev. Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-37024-5","article-title":"Mammalian plasma fetuin-B is a selective inhibitor of ovastacin and meprin metalloproteinases","volume":"9","author":"Karmilin","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_104","first-page":"339","article-title":"Zinc and male reproduction in domestic animals: A Review","volume":"30","author":"Roy","year":"2013","journal-title":"Indian J. Anim. Nutr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev-physiol-030212-183708","article-title":"Estrogen and cancer","volume":"75","author":"Liang","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_106","first-page":"491","article-title":"Do sperm possess a molecular passport? Mechanistic insights into sperm selection in the female reproductive tract","volume":"21","author":"Holt","year":"2015","journal-title":"MHR: Basic Sci. Reprod. Med."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Pfaus, J.G., Jones, S.L., Flanagan-Cato, L.M., and Blaustein, J.D. (2015). Female sexual behavior. Physiology of Reproduction, Elsevier.","DOI":"10.1016\/B978-0-12-397175-3.00050-8"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/humupd\/dmv040","article-title":"Oocyte activation deficiency: A role for an oocyte contribution?","volume":"22","author":"Yeste","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_109","first-page":"289","article-title":"Biological basis for human capacitation\u2014revisited","volume":"23","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/nchem.2133","article-title":"Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks","volume":"7","author":"Que","year":"2019","journal-title":"Nat. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1071\/RD14012","article-title":"Protein deubiquitination during oocyte maturation influences sperm function during fertilisation, antipolyspermy defense and embryo development","volume":"27","author":"Yi","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.4161\/cc.29461","article-title":"Izumo meets Juno: Preventing polyspermy in fertilization","volume":"13","author":"Bianchi","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ymeth.2015.11.003","article-title":"Using in vivo imaging to measure RNA mobility in Xenopus laevis oocytes","volume":"98","author":"Powrie","year":"2016","journal-title":"Methods"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1021\/es305120x","article-title":"Inhibition mechanisms of Zn precipitation on aluminum oxide by glyphosate: A 31P NMR and Zn EXAFS study","volume":"47","author":"Li","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref_115","unstructured":"Hamad, A.M. (2017). Molecular and Physical Interactions of Human Sperm with Female Tract Secretions. [Ph.D. Thesis, University of Birmingham]."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Kerns, K., Sharif, M., Zigo, M., Xu, W., Hamilton, L.E., Sutovsky, M., Ellersieck, M., Drobnis, E.Z., Bovin, N., and Oko, R. (2020). Sperm cohort-specific zinc signature acquisition and capacitation-induced zinc flux regulate sperm-oviduct and sperm-zona pellucida interactions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062121"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"711","DOI":"10.4103\/1008-682X.155769","article-title":"From the epididymis to the egg: Participation of CRISP proteins in mammalian fertilization","volume":"17","author":"Battistone","year":"2015","journal-title":"Asian J. Androl."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.fertnstert.2016.07.1101","article-title":"Seminal fluid and fertility in women","volume":"106","author":"Robertson","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1080\/02772248.2015.1101110","article-title":"Influence of hypothyroidism on oxidative stress, c-Fos expression, cell cycle, and apoptosis in rats testes","volume":"97","author":"Wang","year":"2015","journal-title":"Toxicol. Environ. Chem."},{"key":"ref_120","first-page":"48","article-title":"Sexual Dysfunction in Men and Women with Chronic Kidney Disease and end-stage kidney disease","volume":"10","author":"Palmer","year":"2003","journal-title":"Adv. Ren. Replace."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"6301","DOI":"10.1093\/hmg\/ddv338","article-title":"High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism","volume":"24","author":"Aarabi","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s12011-016-0767-3","article-title":"Dietary zinc oxide modulates antioxidant capacity, small intestine development, and jejunal gene expression in weaned piglets","volume":"175","author":"Zhu","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_123","first-page":"482","article-title":"Progression of the erectile dysfunction in the population and the possibilities of its regression with bioregeneration","volume":"34","author":"Wendlova","year":"2013","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3390\/nu7010153","article-title":"A review of the impact of dietary intakes in human pregnancy on infant birthweight","volume":"7","author":"Grieger","year":"2015","journal-title":"Nutrients"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3109\/01480545.2012.710631","article-title":"Environmental and occupational exposure of metals and their role in male reproductive functions","volume":"36","author":"Sengupta","year":"2013","journal-title":"Drug Chem. Toxicol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"10561","DOI":"10.1007\/s11356-014-2970-0","article-title":"Cadmium as a possible cause of bladder cancer: A review of accumulated evidence","volume":"21","year":"2014","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.siny.2017.02.006","article-title":"Early neonatal death: A challenge worldwide","volume":"22","author":"Lehtonen","year":"2017","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3945\/ajcn.115.111336","article-title":"Lipid-based nutrient supplements for pregnant women reduce newborn stunting in a cluster-randomized controlled effectiveness trial in Bangladesh","volume":"103","author":"Mridha","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5455\/ijmsph.2013.2.1-6","article-title":"Zinc: The trace element of major importance in human nutrition and health","volume":"2","author":"Deshpande","year":"2013","journal-title":"Int. J. Med. Sci. Public Health"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1740-8709.2012.00430.x","article-title":"Maternal selenium, copper and zinc concentrations in pregnancy associated with small-for-gestational-age infants","volume":"10","author":"Mistry","year":"2014","journal-title":"Matern. Child Nutr."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"39","DOI":"10.6000\/1929-4247.2013.02.01.7","article-title":"Nutrient intakes and nutritional status of mothers and their under-five children in a rural community of Oyo state, Nigeria","volume":"2","author":"Fabunmi","year":"2013","journal-title":"Int. J. Child Health Nutr."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.mad.2013.11.009","article-title":"Water-loss dehydration and aging","volume":"136","author":"Hooper","year":"2014","journal-title":"Mech. Ageing Dev."},{"key":"ref_133","first-page":"SC01","article-title":"Study of serum zinc in low birth weight neonates and its relation with maternal zinc","volume":"9","author":"Jyotsna","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.3390\/nu7031744","article-title":"Micronutrients in pregnancy in low-and middle-income countries","volume":"7","author":"Mkparu","year":"2015","journal-title":"Nutrients"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"8770","DOI":"10.1021\/acsomega.7b01404","article-title":"Oxytocin-monolayer-based impedimetric biosensor for zinc and copper ions","volume":"2","author":"Tadi","year":"2017","journal-title":"ACS Omega"},{"key":"ref_136","first-page":"771","article-title":"Frequency, causes and outcome of neonates with respiratory distress admitted to Neonatal Intensive Care Unit, National Institute of Child Health, Karachi","volume":"65","author":"Parkash","year":"2015","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_137","first-page":"343","article-title":"Role of trace elements for oxidative status and quality of human sperm","volume":"34","author":"Nenkova","year":"2017","journal-title":"Balk. Med. J."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1530\/REP-07-0145","article-title":"The role of Zn-\u03b12 glycoprotein in sperm motility is mediated by changes in cyclic AMP","volume":"134","author":"Qu","year":"2007","journal-title":"Reproduction"},{"key":"ref_139","first-page":"76","article-title":"Status of zinc and copper concentrations in seminal plasma of male infertility and their correlation with various sperm parameters","volume":"7","author":"Saleh","year":"2008","journal-title":"Iraqi Acad. Sci. J."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.nutres.2008.11.007","article-title":"Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men","volume":"29","author":"Colagar","year":"2009","journal-title":"Nutr. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"124","DOI":"10.4103\/0974-1208.74153","article-title":"Relationship between seminal plasma zinc and semen quality in a subfertile population","volume":"3","author":"Dissanayake","year":"2010","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4103\/2229-516X.91152","article-title":"Assessment of the level of trace element zinc in seminal plasma of males and evaluation of its role in male infertility","volume":"1","author":"Khan","year":"2011","journal-title":"Int. J. Appl. Basic Med. Res."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Hadwan, M.H., Almashhedy, L.A., and Alsalman, A.R.S. (2012). Oral zinc supplementation restore high molecular weight seminal zinc binding protein to normal value in Iraqi infertile men. BMC Urol., 12.","DOI":"10.1186\/1471-2490-12-32"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.3906\/sag-1211-54","article-title":"Influence of trace elements and their correlation with semen quality in fertile and infertile subjects","volume":"43","author":"Sundaram","year":"2013","journal-title":"Turk. J. Med. Sci."},{"key":"ref_145","first-page":"533","article-title":"Levels of Zinc and Copper in seminal plasma of Sudanese infertile males","volume":"5","author":"Altaher","year":"2015","journal-title":"J. Adv. Med. Med. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"22386","DOI":"10.1038\/srep22386","article-title":"Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis","volume":"6","author":"Zhao","year":"2016","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/2188\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:26:42Z","timestamp":1760160402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/2188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,22]]},"references-count":146,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22042188"],"URL":"https:\/\/doi.org\/10.3390\/ijms22042188","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,22]]}}}