{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:37:51Z","timestamp":1790703471865,"version":"4.1.0"},"reference-count":110,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MUR-PRIN","award":["P2022HYWNR"],"award-info":[{"award-number":["P2022HYWNR"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Smoking habits (from classic cigarettes to e-cigarettes and heated tobacco) are a relatively common finding in the medical histories of couples referred to fertility centers. Tobacco smoke and e-cigarettes may deliver many substances with known harmful effects on both general and reproductive health, including nicotine. Nicotinic Acetylcholine receptors (nAChRs) form a heterogeneous family of ion channels that are differently expressed in different tissues. According to the homomeric or heteromeric combination of at least five different subunits (named from \u03b1 to \u03b5), they have peculiar pharmacological and biophysical properties. nAChRs respond to the neurotransmitter acetylcholine, which influences a number of physiological functions not restricted to neurons and plays an important role in the structure and function of non-neuronal tissues such as the testis. nAChRs are also the target of Nicotine, the active element responsible for tobacco addiction. This review summarizes recent findings on the involvement of nAChRs in testicular physiology, highlighting the effects of nicotine exposure observed in animal studies and clinical settings. We will discuss the latest data on fertility outcomes and the implications for understanding nAChR functions in reproductive health.<\/jats:p>","DOI":"10.3390\/jcm13175097","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:57:06Z","timestamp":1724817426000},"page":"5097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Smoky Impact of Nicotinic Acetylcholine Receptors on Testicular Function"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-370X","authenticated-orcid":false,"given":"Federica","family":"Barbagallo","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-7163","authenticated-orcid":false,"given":"Maria Rita","family":"Assenza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5820-9160","authenticated-orcid":false,"given":"Filippo","family":"Torrisi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-2101","authenticated-orcid":false,"given":"Alessandra","family":"Buonacquisto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6042-6474","authenticated-orcid":false,"given":"Francesco","family":"Pallotti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"},{"name":"Endocrinology and Diabetology Unit, Hospital Umberto I, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021). WHO Global Report on Trends in Prevalence of Tobacco Use 2000\u20132025, WHO Press. [4th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.eururo.2016.04.010","article-title":"Cigarette Smoking and Semen Quality: A New Meta-Analysis Examining the Effect of the 2010 World Health Organization Laboratory Methods for the Examination of Human Semen","volume":"70","author":"Sharma","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1007\/s00216-024-05126-x","article-title":"Non-Targeted Analytical Comparison of a Heated Tobacco Product Aerosol against Mainstream Cigarette Smoke: Does Heating Tobacco Produce an Inherently Different Set of Aerosol Constituents?","volume":"416","author":"Lang","year":"2024","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41572-022-00346-w","article-title":"Tobacco and Nicotine Use","volume":"8","author":"Piper","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.toxrep.2021.01.014","article-title":"Systematic Review of Biomarker Findings from Clinical Studies of Electronic Cigarettes and Heated Tobacco Products","volume":"8","author":"Akiyama","year":"2021","journal-title":"Toxicol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Upadhyay, S., Rahman, M., Johanson, G., Palmberg, L., and Ganguly, K. (2023). Heated Tobacco Products: Insights into Composition and Toxicity. Toxics, 11.","DOI":"10.3390\/toxics11080667"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1021\/acs.chemrestox.4c00093","article-title":"Harmful and Potentially Harmful Constituents in E-Liquids and Aerosols from Electronic Nicotine Delivery Systems (ENDS)","volume":"37","author":"Reilly","year":"2024","journal-title":"Chem. Res. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Campolo, F., Capponi, C., Tarsitano, M.G., Tenuta, M., Pozza, C., Gianfrilli, D., Magliocca, F., Venneri, M.A., Vicini, E., and Lenzi, A. (2022). CAMP-Specific Phosphodiesterase 8A and 8B Isoforms Are Differentially Expressed in Human Testis and Leydig Cell Tumor. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1010924"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.celrep.2018.10.026","article-title":"The Mammalian Spermatogenesis Single-Cell Transcriptome, from Spermatogonial Stem Cells to Spermatids","volume":"25","author":"Hermann","year":"2018","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Khanehzad, M., Abbaszadeh, R., Holakuyee, M., Modarressi, M.H., and Nourashrafeddin, S.M. (2021). FSH Regulates RA Signaling to Commit Spermatogonia into Differentiation Pathway and Meiosis. Reprod. Biol. Endocrinol., 19.","DOI":"10.1186\/s12958-020-00686-w"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10254-003-0005-1","article-title":"Nicotinic Acetylcholine Receptors: From Structure to Brain Function","volume":"147","author":"Hogg","year":"2003","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.pharmthera.2012.08.012","article-title":"Nicotinic Acetylcholine Receptors: From Basic Science to Therapeutics","volume":"137","author":"Hurst","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/978-1-4899-1775-1_10","article-title":"Neuronal Nicotinic Acetylcholine Receptors","volume":"4","author":"Lindstrom","year":"1996","journal-title":"Ion. Channels"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.intimp.2015.04.015","article-title":"Non-Neuronal Cholinergic System in Regulation of Immune Function with a Focus on \u03b17 NAChRs","volume":"29","author":"Kawashima","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1124\/mol.54.5.779","article-title":"Human and Rodent Bronchial Epithelial Cells Express Functional Nicotinic Acetylcholine Receptors","volume":"54","author":"Maus","year":"1998","journal-title":"Mol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/jidsymp.1997.10","article-title":"Biological Functions of Keratinocyte Cholinergic Receptors","volume":"2","author":"Grando","year":"1997","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s12031-009-9268-6","article-title":"Muscarinic Acetylcholine Receptor Subtypes in the Male Reproductive Tract","volume":"40","author":"Avellar","year":"2010","journal-title":"J. Mol. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1530\/REP-10-0302","article-title":"The Cholinergic System in Rat Testis Is of Non-Neuronal Origin","volume":"142","author":"Schirmer","year":"2011","journal-title":"Reproduction"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"dev174953","DOI":"10.1242\/dev.174953","article-title":"Revealing Cellular and Molecular Transitions in Neonatal Germ Cell Differentiation Using Single Cell RNA Sequencing","volume":"146","author":"Liao","year":"2019","journal-title":"Development"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1242\/dev.032243","article-title":"Colony Stimulating Factor 1 Is an Extrinsic Stimulator of Mouse Spermatogonial Stem Cell Self-Renewal","volume":"136","author":"Oatley","year":"2009","journal-title":"Development"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14184","DOI":"10.1111\/jcmm.16029","article-title":"Cisatracurium Stimulates Testosterone Synthesis in Rat and Mouse Leydig Cells via Nicotinic Acetylcholine Receptor","volume":"24","author":"Ni","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_22","first-page":"8892217","article-title":"Fetal and Postnatal Nicotine Exposure Modifies Maturation of Gonocytes to Spermatogonia in Mice","volume":"2020","author":"Espinosa","year":"2020","journal-title":"Anal. Cell. Pathol."},{"key":"ref_23","first-page":"333","article-title":"Inhibitory Role of Cholinergic Agonists on Testosterone Secretion by Purified Rat Leydig Cells","volume":"101","author":"Favaretto","year":"1993","journal-title":"Arch. Int. Physiol. Biochim. Biophys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1095\/biolreprod.104.037499","article-title":"Gene Expression in Rat Leydig Cells During Development from the Progenitor to Adult Stage: A Cluster Analysis1","volume":"72","author":"Ge","year":"2005","journal-title":"Biol. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Makino, Y., Hiradate, Y., Umezu, K., Hara, K., and Tanemura, K. (2021). Expression and Possible Role of Nicotinic Acetylcholine Receptor \u03b5 Subunit (Achre) in Mouse Sperm. Biology, 10.","DOI":"10.3390\/biology10010046"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1017\/S0967199400002604","article-title":"Localisation of Two Classes of Acetylcholine Receptor-like Molecules in Sperms of Different Animal Species","volume":"3","author":"Baccetti","year":"1995","journal-title":"Zygote"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1095\/biolreprod.105.042184","article-title":"Mice Deficient in CHRNA7, a Subunit of the Nicotinic Acetylcholine Receptor, Produce Sperm with Impaired Motility1","volume":"73","author":"Bray","year":"2005","journal-title":"Biol. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25928","DOI":"10.1074\/jbc.M502435200","article-title":"Nicotinic Acetylcholine Receptor Subunits and Associated Proteins InHuman Sperm","volume":"280","author":"Kumar","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Condorelli, R.A., La Vignera, S., Giacone, F., Iacoviello, L., Mongio\u00ec, L.M., Volti, G.L., Barbagallo, I., Avola, R., and Calogero, A.E. (2017). Nicotine Effects and Receptor Expression on Human Spermatozoa: Possible Neuroendocrine Mechanism. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00177"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1093\/molehr\/gah245","article-title":"Acetylcholine Causes an Increase of Intracellular Calcium in Human Sperm","volume":"11","author":"Bray","year":"2005","journal-title":"MHR Basic. Sci. Reprod. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1095\/biolreprod.102.004580","article-title":"A Nicotinic Acetylcholine Receptor Is Involved in the Acrosome Reaction of Human Sperm Initiated by Recombinant Human ZP31","volume":"67","author":"Bray","year":"2002","journal-title":"Biol. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.1073\/pnas.88.9.3676","article-title":"Expression of Choline Acetyltransferase MRNA in Spermatogenic Cells Results in an Accumulation of the Enzyme in the Postacrosomal Region of Mature Spermatozoa","volume":"88","author":"Hersh","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1095\/biolreprod.102.011163","article-title":"Evidence Suggesting That the Mouse Sperm Acrosome Reaction Initiated by the Zona Pellucida Involves an \u03b17 Nicotinic Acetylcholine Receptor1","volume":"68","author":"Son","year":"2003","journal-title":"Biol. Reprod."},{"key":"ref_34","first-page":"9165","article-title":"Mice Deficient in the 7 Neuronal Nicotinic Acetylcholine Receptor Lack-Bungarotoxin Binding Sites and Hippocampal Fast Nicotinic Currents","volume":"17","author":"Saeki","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-3-540-69248-5_12","article-title":"Effects of Nicotine in Experimental Animals and Humans: An Update on Addictive Properties","volume":"192","author":"Goldberg","year":"2009","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rodgman, A., and Perfetti, T.A. (2008). The Chemical Components of Tobacco and Tobacco Smoke, CRC Press. [1st ed.].","DOI":"10.1201\/9781420078848"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1046\/j.1464-4096.2001.02384.x","article-title":"Nicotine Toxicity to the Ultrastructure of the Testis in Rats","volume":"88","author":"Aydos","year":"2001","journal-title":"BJU Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000028262","article-title":"Nicotine Administration Induced Changes in the Gonadal Functions in Male Rats","volume":"58","author":"Kavitharaj","year":"1999","journal-title":"Pharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.etp.2015.01.001","article-title":"Nicotine-Induced Reproductive Toxicity, Oxidative Damage, Histological Changes and Haematotoxicity in Male Rats: The Protective Effects of Green Tea Extract","volume":"67","author":"Mosbah","year":"2015","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.reprotox.2010.12.004","article-title":"Effect of in Utero and Lactational Nicotine Exposure on the Male Reproductive Tract in Peripubertal and Adult Rats","volume":"31","author":"Lagunov","year":"2011","journal-title":"Reprod. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1530\/REP-15-0135","article-title":"Prenatal and Lactation Nicotine Exposure Affects Sertoli Cell and Gonadotropin Levels in Rats","volume":"151","author":"Paccola","year":"2016","journal-title":"Reproduction"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ijheh.2014.08.006","article-title":"Effect of Cigarette Smoke on DNA Damage, Oxidative Stress, and Morphological Alterations in Mouse Testis and Spermatozoa","volume":"218","author":"Micale","year":"2015","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/mrd.22863","article-title":"Cigarette Smoke Induces Rat Testicular Injury via Mitochondrial Apoptotic Pathway","volume":"84","author":"He","year":"2017","journal-title":"Mol. Reprod. Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.freeradbiomed.2023.02.024","article-title":"The Role of Ferroptosis Mediated by Bmal1\/Nrf2 in Nicotine -Induce Injury of BTB Integrity","volume":"200","author":"Zhang","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1159\/000020061","article-title":"Ultrastructural Effects of Cigarette Smoke on Rat Testis","volume":"36","author":"Can","year":"1999","journal-title":"Eur. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104882","DOI":"10.1016\/j.tiv.2020.104882","article-title":"Effects of Nicotine on Porcine Pre-Pupertal Sertoli Cells: An In Vitro Study","volume":"67","author":"Marinucci","year":"2020","journal-title":"Toxicol. Vitro"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1111\/andr.12072","article-title":"Nicotine Elevates Sperm Motility and Induces Pfn1 Promoter Hypomethylation in Mouse Testis","volume":"3","author":"Dai","year":"2015","journal-title":"Andrology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.bbrc.2016.03.044","article-title":"Nicotine Induces Nme2-Mediated Apoptosis in Mouse Testes","volume":"472","author":"Gu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s002400050022","article-title":"Effects of Smoking on Testicular Function and Fertilizing Potential in Rats","volume":"26","author":"Yamamoto","year":"1998","journal-title":"Urol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4103\/0974-1208.112380","article-title":"Nicotine Alters Male Reproductive Hormones in Male Albino Rats: The Role of Cessation","volume":"6","author":"Oyeyipo","year":"2013","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1093\/humrep\/dei148","article-title":"Chronic Chromium Exposure-Induced Changes in Testicular Histoarchitecture Are Associated with Oxidative Stress: Study in a Non-Human Primate (Macaca Radiata Geoffroy)","volume":"20","author":"Aruldhas","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s12011-007-8021-7","article-title":"Protective Effect of Selenium on Nicotine-Induced Testicular Toxicity in Rats","volume":"120","author":"Seema","year":"2007","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ejphar.2006.10.008","article-title":"Effects of Nicotine and Vitamin E on Glutathione Reductase Activity in Some Rat Tissues in Vivo and in Vitro","volume":"554","author":"Erat","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"232","DOI":"10.5115\/acb.20.161","article-title":"The Amelioration of Nicotine-Induced Reproductive Impairment in Male Mouse by Sambucus ebulus L.","volume":"54","author":"Mohammadghasemi","year":"2021","journal-title":"Fruit. Extract. Anat. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4103\/0974-1208.130823","article-title":"Antioxidant Profile Changes in Reproductive Tissues of Rats Treated with Nicotine","volume":"7","author":"Oyeyipo","year":"2014","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/toxsci\/kfq149","article-title":"Nicotine Diminishes Testicular Gametogenesis, Steroidogenesis, and Steroidogenic Acute Regulatory Protein Expression in Adult Albino Rats: Possible Influence on Pituitary Gonadotropins and Alteration of Testicular Antioxidant Status","volume":"116","author":"Jana","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0890-6238(02)00119-3","article-title":"Adrenal-Mediated Rather than Direct Effects of Nicotine as a Basis of Altered Sex Steroid Synthesis in Fetal and Neonatal Rat","volume":"17","author":"Sarasin","year":"2003","journal-title":"Reprod. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.biocel.2018.05.001","article-title":"Nicotine Induced Autophagy of Leydig Cells Rather than Apoptosis Is the Major Reason of the Decrease of Serum Testosterone","volume":"100","author":"Zhao","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2018.11.107","article-title":"Nicotine Inhibits Murine Leydig Cell Differentiation and Maturation via Regulating Hedgehog Signal Pathway","volume":"510","author":"Wu","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.fct.2017.09.055","article-title":"Nicotine Affects Rat Leydig Cell Function in Vivo and Vitro via Down-Regulating Some Key Steroidogenic Enzyme Expressions","volume":"110","author":"Guo","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/0022-4731(89)90051-4","article-title":"Nicotine and Cotinine Inhibit Rat Testis Androgen Biosynthesis in Vitro","volume":"33","author":"Yeh","year":"1989","journal-title":"J. Steroid Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1677\/JME-07-0051","article-title":"Folding, Activity and Import of Steroidogenic Acute Regulatory Protein into Mitochondria Changed by Nicotine Exposure","volume":"39","author":"Bose","year":"2007","journal-title":"J. Mol. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"274048","DOI":"10.1155\/2014\/274048","article-title":"Prenatal Exposure to Nicotine in Pregnant Rat Increased Inflammatory Marker in Newborn Rat","volume":"2014","author":"Mohsenzadeh","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4103\/jeca.jeca_10_19","article-title":"Testosterone Propionate Ameliorates Oxidatve Stress and Inflammation in Nicotine-Induced Testicular Toxicity","volume":"18","author":"Ukwenya","year":"2019","journal-title":"J. Exp. Clin. Anat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1177\/0960327113491509","article-title":"Effects of Nicotine on the Testicular Toxicity of Streptozotocin-Induced Diabetic Rat","volume":"33","author":"Kushwaha","year":"2014","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Fan, S.W., Zhang, Z., Wang, H.R., Luo, L., and Xu, B. (2024). Associations between Tobacco Inhalation and Semen Parameters in Men with Primary and Secondary Infertility: A Cross-Sectional Study. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1396793"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1007\/s40618-020-01257-x","article-title":"People Smoke for Nicotine, but Lose Sexual and Reproductive Health for Tar: A Narrative Review on the Effect of Cigarette Smoking on Male Sexuality and Reproduction","volume":"43","author":"Corona","year":"2020","journal-title":"J. Endocrinol. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Montjean, D., Godin Pag\u00e9, M.H., B\u00e9langer, M.C., Benkhalifa, M., and Miron, P. (2023). An Overview of E-Cigarette Impact on Reproductive Health. Life, 13.","DOI":"10.3390\/life13030827"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Pivonello, R., and Diamanti-Kandarakis, E. (2023). Environmental Impact on Semen Quality and Male Fertility. Environmental Endocrinology and Endocrine Disruptors: Endocrine and Endocrine-Targeted Actions and Related Human Diseases, Springer International Publishing.","DOI":"10.1007\/978-3-030-39044-0"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1007\/s12011-021-02720-3","article-title":"Evaluating the Serum and Seminal Plasma Levels of Zinc and Cadmium in Smokers and Their Relation to the Semen Parameters","volume":"200","author":"Bazid","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1007\/s11356-018-3748-6","article-title":"Relationship between Cadmium Content in Semen and Male Infertility: A Meta-Analysis","volume":"26","author":"Zhang","year":"2019","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"108387","DOI":"10.1016\/j.reprotox.2023.108387","article-title":"The Influence of Lead Exposure on Male Semen Parameters: A Systematic Review and Meta-Analysis","volume":"118","author":"Giulioni","year":"2023","journal-title":"Reprod. Toxicol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"125498","DOI":"10.1016\/j.chemosphere.2019.125498","article-title":"Heavy Metal Exposure, Oxidative Stress and Semen Quality: Exploring Associations and Mediation Effects in Reproductive-Aged Men","volume":"244","author":"He","year":"2020","journal-title":"Chemosphere"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12011-016-0804-2","article-title":"Heavy Metal Level in Human Semen with Different Fertility: A Meta-Analysis","volume":"176","author":"Sun","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1097\/00007691-199310000-00002","article-title":"Nicotine, Cotinine, and Trans-3-Hydroxycotine Levels in Seminal Plasma of Smokers: Effects on Sperm Parameters","volume":"15","author":"Pacifici","year":"1993","journal-title":"Ther. Drug Monit."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Dill, M., Deconinck, E., and Barhdadi, S. (2024). Method Development and Validation of an Aerosol Sampling Technique for the Analysis of Nicotine in Electronic Cigarette Aerosols. Molecules, 29.","DOI":"10.3390\/molecules29153487"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1007\/s00216-020-02502-1","article-title":"Comprehensive Chemical Characterization of the Aerosol Generated by a Heated Tobacco Product by Untargeted Screening","volume":"412","author":"Bentley","year":"2020","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/08958378.2022.2103602","article-title":"Composition of Aerosols from Thermal Degradation of Flavors Used in ENDS and Tobacco Products","volume":"34","author":"Kuehl","year":"2022","journal-title":"Inhal. Toxicol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"100067","DOI":"10.1016\/j.crtox.2022.100067","article-title":"Assessment of Nicotine Delivery and Uptake in Users of Various Tobacco\/Nicotine Products","volume":"3","author":"Scherer","year":"2022","journal-title":"Curr. Res. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Christen, S.E., Hermann, L., Bekka, E., Vonwyl, C., Hammann, F., van der Velpen, V., Eap, C.B., Benowitz, N.L., Haschke, M., and Liakoni, E. (2024). Pharmacokinetics and Pharmacodynamics of Inhaled Nicotine Salt and Free-Base Using an E-Cigarette: A Randomized Crossover Study. Nicotine Tob. Res., ahead of print.","DOI":"10.1093\/ntr\/ntae074"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/humrep\/12.4.727","article-title":"The In-Vitro Effects of Nicotine and Cotinine on Sperm Motility","volume":"12","author":"Gandini","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.rbmo.2009.05.004","article-title":"Cigarette Smoke Extract Immobilizes Human Spermatozoa and Induces Sperm Apoptosis","volume":"19","author":"Calogero","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S412","DOI":"10.4103\/jpbs.jpbs_635_23","article-title":"Effect of Tobacco Use on Semen in Infertile Male","volume":"6","author":"Kanetkar","year":"2024","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e13090","DOI":"10.1111\/and.13090","article-title":"Paternal Lifestyle Factors in Relation to Semen Quality and In Vitro Reproductive Outcomes","volume":"50","author":"Borges","year":"2018","journal-title":"Andrologia"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1093\/humrep\/deaa089","article-title":"Use of E-Cigarettes Associated with Lower Sperm Counts in a Cross-Sectional Study of Young Men from the General Population","volume":"35","author":"Holmboe","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1093\/humrep\/deu347","article-title":"Current Smoking Is Associated with Lower Seminal Vesicles and Ejaculate Volume, despite Higher Testosterone Levels, in Male Subjects of Infertile Couples","volume":"30","author":"Lotti","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_87","first-page":"e54051","article-title":"Effectiveness of Healthcare Interventions on Smoking Cessation in Adolescents in Low- and Middle-Income Countries: A Narrative Review","volume":"16","author":"Thakur","year":"2024","journal-title":"Cureus"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/ntr\/ntv227","article-title":"Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam With Improper Palatal Fusion","volume":"18","author":"Ozturk","year":"2016","journal-title":"Nicotine Tob. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.55730\/1300-0144.5527","article-title":"Enhancing Effect of Nicotine on Electrical Field Stimulation Elicited Contractile Responses in Isolated Rabbit Bladder Straight Muscle; the Role of Cannabinoid and Vanilloid Receptors","volume":"52","author":"Fincan","year":"2022","journal-title":"Turk. J. Med. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ypmed.2015.12.021","article-title":"Cigarette Smoking and Testosterone in Men and Women: A Systematic Review and Meta-Analysis of Observational Studies","volume":"85","author":"Zhao","year":"2016","journal-title":"Prev. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e13409","DOI":"10.1111\/and.13409","article-title":"Correlation of Plasma Kisspeptin with Total Testosterone Levels in Smokeless Tobacco and Smoking Tobacco Users in a Healthy Cohort: A Cross-Sectional Study","volume":"51","author":"Shah","year":"2019","journal-title":"Andrologia"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1111\/andr.13198","article-title":"Decreased Sperm Counts in Swedish Users of Oral Tobacco","volume":"10","author":"Kimblad","year":"2022","journal-title":"Andrology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s40618-022-01741-6","article-title":"Management of Male Factor Infertility: Position Statement from the Italian Society of Andrology and Sexual Medicine (SIAMS): Endorsing Organization: Italian Society of Embryology, Reproduction, and Research (SIERR)","volume":"45","author":"Ferlin","year":"2022","journal-title":"J. Endocrinol. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1093\/toxres\/tfaa031","article-title":"The Effect of Different Tobacco Tar Levels on DNA Damage in Cigarette Smoking Subjects","volume":"9","author":"Zhao","year":"2020","journal-title":"Toxicol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Morgil, G.K., and \u00c7ok, \u0130. (2024). Evaluation and Comparison of DNA Alkylation and Oxidative Damage in E-Cigarette and Heated Tobacco Users. Toxicol. Mech. Methods, 1\u201311.","DOI":"10.1080\/15376516.2024.2390028"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e000452","DOI":"10.1136\/bmjresp-2019-000452","article-title":"Correlation between Biomarkers of Exposure, Effect and Potential Harm in the Urine of Electronic Cigarette Users","volume":"7","author":"Williams","year":"2020","journal-title":"BMJ Open Respir. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0890-6238(97)00032-4","article-title":"Detection of Oxidative Dna Damage in Human Sperm and the Association with Cigarette Smoking","volume":"11","author":"Shen","year":"1997","journal-title":"Reprod. Toxicol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Conflitti, A.C., Cicolani, G., Buonacquisto, A., Pallotti, F., Faja, F., Bianchini, S., Blacon\u00e0, G., Bruno, S.M., Linari, A., and Lucarelli, M. (2023). Sperm DNA Fragmentation and Sperm-Borne MiRNAs: Molecular Biomarkers of Embryo Development?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021007"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Paoli, D., Pallotti, F., Lenzi, A., and Lombardo, F. (2018). Fatherhood and Sperm DNA Damage in Testicular Cancer Patients. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00506"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Szab\u00f3, A., V\u00e1ncsa, S., Hegyi, P., V\u00e1radi, A., Forintos, A., Filipov, T., \u00c1cs, J., \u00c1cs, N., Szarvas, T., and Nyir\u00e1dy, P. (2023). Lifestyle-, Environmental-, and Additional Health Factors Associated with an Increased Sperm DNA Fragmentation: A Systematic Review and Meta-Analysis. Reprod. Biol. Endocrinol., 21.","DOI":"10.1186\/s12958-023-01054-0"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"62055","DOI":"10.1007\/s11356-021-16331-x","article-title":"The Mutagenic Effect of Tobacco Smoke on Male Fertility","volume":"29","author":"Omolaoye","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1093\/humrep\/deq226","article-title":"Protamine Contents and P1\/P2 Ratio in Human Spermatozoa from Smokers and Non-Smokers","volume":"25","author":"Hammadeh","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Colacurci, N., De Leo, V., Ruvolo, G., Piomboni, P., Caprio, F., Pivonello, R., Papaleo, E., La Verde, E., Depalo, R., and Lispi, M. (2018). Recombinant FSH Improves Sperm DNA Damage in Male Infertility: A Phase II Clinical Trial. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00383"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/humupd\/dmaa025","article-title":"DNA Methylation in Human Sperm: A Systematic Review","volume":"26","author":"Danson","year":"2020","journal-title":"Hum. Reprod. Update"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"26835","DOI":"10.1007\/s11356-021-17786-8","article-title":"Cigarette Heavy Smoking Alters DNA Methylation Patterns and Gene Transcription Levels in Humans Spermatozoa","volume":"29","author":"Laqqan","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"432","DOI":"10.4161\/epi.19794","article-title":"Smoking Induces Differential MiRNA Expression in Human Spermatozoa: A Potential Transgenerational Epigenetic Concern?","volume":"7","author":"Marczylo","year":"2012","journal-title":"Epigenetics"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Ajayi, A.F., Oyovwi, M.O., Olatinwo, G., and Phillips, A.O. (2024). Unfolding the Complexity of Epigenetics in Male Reproductive Aging: A Review of Therapeutic Implications. Mol. Biol. Rep., 51.","DOI":"10.1007\/s11033-024-09823-9"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Manetti, D., Dei, S., Arias, H.R., Braconi, L., Gabellini, A., Teodori, E., and Romanelli, M.N. (2023). Recent Advances in the Discovery of Nicotinic Acetylcholine Receptor Allosteric Modulators. Molecules, 28.","DOI":"10.3390\/molecules28031270"},{"key":"ref_109","first-page":"e61951","article-title":"Role of Dietary Antioxidant Supplements in Male Infertility: A Review","volume":"16","author":"Ghewade","year":"2024","journal-title":"Cureus"},{"key":"ref_110","first-page":"433","article-title":"The Role of microRNAs in Nicotine Signaling","volume":"22","author":"Hajiasgharzadeh","year":"2023","journal-title":"EXCLI J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/17\/5097\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:44:02Z","timestamp":1760111042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/17\/5097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":110,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["jcm13175097"],"URL":"https:\/\/doi.org\/10.3390\/jcm13175097","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,28]]}}}