{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:42:02Z","timestamp":1776166922356,"version":"3.50.1"},"reference-count":252,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The World Health Organization (WHO) defines infertility as the inability of a couple to conceive after at least 12 months of regular, unprotected sexual intercourse. The male factor appears to be contributing, solely or in combination with other causes, to approximately 50% of all infertility cases. Several etiological factors of male infertility have been identified; however, the exact molecular mechanisms underlying sperm dysfunction are not yet fully understood. Aldehyde dehydrogenases (ALDHs) are multifaceted metabolic enzymes that catalyze the detoxification of several aldehydes, thus acting as antioxidants, while they regulate additional homeostatic functions by contributing to retinoic acid (RA) synthesis. Consequently, they have been identified as crucial factors in various pathogenetic mechanisms. ALDHs hold physiological roles in the testis through supporting the Sertoli cell function, the steroidogenesis in Leydig cells, and the maintenance of sperm integrity. Current evidence supports that dysregulation of specific ALDHs isoforms could be associated with disrupted testicular cell function, including oxidative imbalance and altered RA synthesis. These irregularities could interfere with germ cell development and, subsequently, contribute to decline in reproductive function. In this paper, we are reviewing the role of ALDHs in male reproduction and how their dysregulation could be implicated in male infertility. Unraveling the mechanisms underlying the association of ALDHs with male reproductive function could hold clinical interest regarding the development of novel approaches for enhancing male fertility.<\/jats:p>","DOI":"10.3390\/ph19040617","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:29:08Z","timestamp":1776162548000},"page":"617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reviewing the Implication of Aldehyde Dehydrogenases in Male Reproduction: Prospects for New Therapeutic Approaches"],"prefix":"10.3390","volume":"19","author":[{"given":"Foteini","family":"Gkaitatzi","sequence":"first","affiliation":[{"name":"PEDY\u2014National Primary Health Care Network, 68132 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1607-7470","authenticated-orcid":false,"given":"Ilias","family":"Tsochantaridis","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Pagonopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Neurophysiology, Department of Medicine, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-8560","authenticated-orcid":false,"given":"Georgia-Persephoni","family":"Voulgaridou","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Medicine, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male Infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"ref_2","unstructured":"World Health Organization (2023). Infertility Prevalence Estimates 1990\u20132021, WHO."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1136\/bmj.291.6510.1693","article-title":"Population Study of Causes, Treatment, and Outcome of Infertility","volume":"291","author":"Hull","year":"1985","journal-title":"Br. Med. J. (Clin. Res. Ed.)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.fertnstert.2020.11.015","article-title":"Diagnosis and Treatment of Infertility in Men: AUA\/ASRM Guideline Part I","volume":"115","author":"Schlegel","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_5","unstructured":"Leslie, S.W., Soon-Sutton, T.L., and Khan, M.A. (2024). Male Infertility. StatPearls, StatPearls Publishing."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1136\/bmj.305.6854.609","article-title":"Evidence for Decreasing Quality of Semen during Past 50 Years","volume":"305","author":"Carlsen","year":"1992","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/humupd\/dmx022","article-title":"Temporal Trends in Sperm Count: A Systematic Review and Meta-Regression Analysis","volume":"23","author":"Levine","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/humupd\/dmac035","article-title":"Temporal Trends in Sperm Count: A Systematic Review and Meta-Regression Analysis of Samples Collected Globally in the 20th and 21st Centuries","volume":"29","author":"Levine","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1289\/ehp.971051228","article-title":"Have Sperm Densities Declined? A Reanalysis of Global Trend Data","volume":"105","author":"Swan","year":"1997","journal-title":"Environ. Health Perspect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101398","DOI":"10.1016\/j.mam.2025.101398","article-title":"Evolution of the Incidence of Male Fertility Disorders over the Last Decades","volume":"105","author":"Pallotti","year":"2025","journal-title":"Mol. Asp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41572-023-00459-w","article-title":"Male Infertility","volume":"9","author":"Eisenberg","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Zachariou, A., Dimitriadis, F., Chrisofos, M., and Sofikitis, N. (2024). Empirical Treatments for Male Infertility: A Focus on Lifestyle Modifications and Medicines. Diseases, 12.","DOI":"10.3390\/diseases12090209"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.eururo.2025.02.026","article-title":"European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2025 Update on Male Infertility","volume":"87","author":"Minhas","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bouhadana, D., Godin Pag\u00e9, M.H., Montjean, D., B\u00e9langer, M.C., Benkhalifa, M., Miron, P., and Petrella, F. (2025). The Role of Antioxidants in Male Fertility: A Comprehensive Review of Mechanisms and Clinical Applications. Antioxidants, 14.","DOI":"10.3390\/antiox14081013"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Xanthis, V., Mantso, T., Dimtsi, A., Pappa, A., and Fadouloglou, V.E. (2023). Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer. Cancers, 15.","DOI":"10.3390\/cancers15174419"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1002\/mco2.195","article-title":"Aldehyde Dehydrogenase in Solid Tumors and Other Diseases: Potential Biomarkers and Therapeutic Targets","volume":"4","author":"Xia","year":"2023","journal-title":"MedComm"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1124\/pr.111.005538","article-title":"Aldehyde Dehydrogenase Inhibitors: A Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application","volume":"64","author":"Koppaka","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s00253-025-13467-5","article-title":"The Aldehyde Dehydrogenase Superfamilies: Correlations and Deviations in Structure and Function","volume":"109","author":"Heider","year":"2025","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tsochantaridis, I., Roupas, A., Mohlin, S., Pappa, A., and Voulgaridou, G.P. (2023). The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression. Life, 13.","DOI":"10.3390\/life13010197"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3904645","DOI":"10.1155\/2019\/3904645","article-title":"Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells","volume":"2019","author":"Vassalli","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"dev167502","DOI":"10.1242\/dev.167502","article-title":"Retinoic Acid Signaling Pathways","volume":"146","author":"Ghyselinck","year":"2019","journal-title":"Development"},{"key":"ref_22","first-page":"dev170225","article-title":"Two Functionally Redundant Sources of Retinoic Acid Secure Spermatogonia Differentiation in the Seminiferous Epithelium","volume":"146","author":"Teletin","year":"2019","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1073\/pnas.1214883110","article-title":"Retinol Dehydrogenase 10 Is Indispensible for Spermatogenesis in Juvenile Males","volume":"110","author":"Tong","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1046\/j.1432-1327.1998.2510549.x","article-title":"Human Aldehyde Dehydrogenase Gene Family","volume":"251","author":"Yoshida","year":"1998","journal-title":"Eur. J. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111622","DOI":"10.1016\/j.cbi.2025.111622","article-title":"Dual Roles and Therapeutic Potential of ALDH3 Family Members in Cancer","volume":"418","author":"Liu","year":"2025","journal-title":"Chem. Biol. Interact."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tsai, H.Y., Hsu, Y.J., Lu, C.Y., Tsai, M.C., Hung, W.C., Chen, P.C., Wang, J.C., Hsu, L.A., Yeh, Y.H., and Chu, P. (2021). Pharmacological Activation of Aldehyde Dehydrogenase 2 Protects Against Heatstroke-Induced Acute Lung Injury by Modulating Oxidative Stress and Endothelial Dysfunction. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.740562"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.freeradbiomed.2010.08.004","article-title":"Molecular Characterization, Expression Analysis, and Role of ALDH3B1 in the Cellular Protection against Oxidative Stress","volume":"49","author":"Marchitti","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s10038-003-0122-3","article-title":"Identification of ALDH4 as a P53-Inducible Gene and Its Protective Role in Cellular Stresses","volume":"49","author":"Yoon","year":"2004","journal-title":"J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"108477","DOI":"10.1016\/j.abb.2020.108477","article-title":"Inhibition, Crystal Structures, and in-Solution Oligomeric Structure of Aldehyde Dehydrogenase 9A1","volume":"691","author":"Wyatt","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3390\/nu3040385","article-title":"Vitamin A in Reproduction and Development","volume":"3","author":"Knutson","year":"2011","journal-title":"Nutrients"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Schubert, M., and Germain, P. (2023). Retinoic Acid and Retinoid X Receptors. Cells, 12.","DOI":"10.3390\/cells12060864"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e23327","DOI":"10.1002\/dvg.23327","article-title":"Retinoic Acid Signaling in Regulation of Meiosis during Embryonic Development in Mice","volume":"57","author":"Yadu","year":"2019","journal-title":"Genesis"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chatzi, C., Brade, T., and Duester, G. (2011). Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia. PLoS Biol., 9.","DOI":"10.1371\/journal.pbio.1000609"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12958-020-00686-w","article-title":"FSH Regulates RA Signaling to Commit Spermatogonia into Differentiation Pathway and Meiosis","volume":"19","author":"Khanehzad","year":"2021","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.tem.2010.03.001","article-title":"Undifferentiated Primate Spermatogonia and Their Endocrine Control","volume":"21","author":"Plant","year":"2010","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.mce.2013.09.026","article-title":"Control of Mammalian Germ Cell Entry into Meiosis","volume":"382","author":"Feng","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R175","DOI":"10.1016\/S0960-9822(98)70104-6","article-title":"Gonad Development: Assembling the Mammalian Testis","volume":"8","author":"McLaren","year":"1998","journal-title":"Curr. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/wdev.62","article-title":"Testis Formation in the Fetal Mouse: Dynamic and Complex de Novo Tubulogenesis","volume":"1","author":"Cool","year":"2012","journal-title":"WIREs Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10796","DOI":"10.1038\/s41598-020-67595-1","article-title":"Germ Cell Depletion in Recipient Testis Has Adverse Effects on Spermatogenesis in Orthotopically Transplanted Testis Pieces via Retinoic Acid Insufficiency","volume":"10","author":"Tsuchimoto","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Deng, S., Li, C., Cao, J., Wu, A., Chen, M., Ma, X., Wu, S., and Lian, Z. (2024). The Role of Retinoic Acid in Spermatogenesis and Its Application in Male Reproduction. Cells, 13.","DOI":"10.3390\/cells13131092"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R151","DOI":"10.1530\/REP-16-0588","article-title":"Role of the Testis Interstitial Compartment in Spermatogonial Stem Cell Function","volume":"153","author":"Potter","year":"2017","journal-title":"Reproduction"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1126\/science.287.5457.1489","article-title":"Regulation of Cell Fate Decision of Undifferentiated Spermatogonia by GDNF","volume":"287","author":"Meng","year":"2000","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1007\/s11626-016-0073-6","article-title":"Amniotic Membrane Mesenchymal Stem Cells Can Differentiate into Germ Cells in Vitro","volume":"52","author":"Afsartala","year":"2016","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1017\/S0967199417000326","article-title":"Morphofunctional Evaluation of the Testis, Duration of Spermatogenesis and Spermatogenic Efficiency in the Japanese Fancy Mouse (Mus musculus molossinus)","volume":"25","author":"Costa","year":"2017","journal-title":"Zygote"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109915","DOI":"10.1016\/j.celrep.2021.109915","article-title":"Dissecting Mammalian Spermatogenesis Using Spatial Transcriptomics","volume":"37","author":"Chen","year":"2021","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E2347","DOI":"10.1073\/pnas.1505683112","article-title":"Periodic Retinoic Acid-STRA8 Signaling Intersects with Periodic Germ-Cell Competencies to Regulate Spermatogenesis","volume":"112","author":"Endo","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E10132","DOI":"10.1073\/pnas.1710837114","article-title":"Periodic Production of Retinoic Acid by Meiotic and Somatic Cells Coordinates Four Transitions in Mouse Spermatogenesis","volume":"114","author":"Endo","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1172\/JCI41303","article-title":"The Key Role of Vitamin A in Spermatogenesis","volume":"120","author":"Hogarth","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1111\/andr.12722","article-title":"Cycles, Waves, and Pulses: Retinoic Acid and the Organization of Spermatogenesis","volume":"8","author":"Gewiss","year":"2020","journal-title":"Andrology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coemr.2019.01.001","article-title":"Retinoic Acid Signaling and the Cycle of the Seminiferous Epithelium","volume":"6","author":"Helsel","year":"2019","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/j.1939-4640.2000.tb03408.x","article-title":"All You Wanted to Know about Spermatogonia but Were Afraid to Ask","volume":"21","author":"Russell","year":"2000","journal-title":"J. Androl."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/andr.12165","article-title":"The Sertoli Cell: One Hundred Fifty Years of Beauty and Plasticity","volume":"4","author":"Hess","year":"2016","journal-title":"Andrology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1095\/biolreprod52.2.217","article-title":"Regulation of Expression of Steroidogenic Enzymes in Leydig Cells","volume":"52","author":"Payne","year":"1995","journal-title":"Biol. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/andr.13386","article-title":"What Are Sertoli Cells? Historical, Methodological, and Functional Aspects","volume":"11","author":"Thumfart","year":"2023","journal-title":"Andrology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00013.2015","article-title":"Spermatogenesis: The Commitment to Meiosis","volume":"96","author":"Griswold","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Christine Schleif, M., Havel, S.L., and Griswold, M.D. (2022). Function of Retinoic Acid in Development of Male and Female Gametes. Nutrients, 14.","DOI":"10.3390\/nu14061293"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.celrep.2015.07.015","article-title":"Macrophages Contribute to the Spermatogonial Niche in the Adult Testis","volume":"12","author":"DeFalco","year":"2015","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4964","DOI":"10.1210\/en.2014-1406","article-title":"Peritubular Myoid Cells Participate in Male Mouse Spermatogonial Stem Cell Maintenance","volume":"155","author":"Chen","year":"2014","journal-title":"Endocrinology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1073\/pnas.1517994113","article-title":"Targeting the Gdnf Gene in Peritubular Myoid Cells Disrupts Undifferentiated Spermatogonial Cell Development","volume":"113","author":"Chen","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.stem.2018.11.013","article-title":"Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche","volume":"24","author":"Kitadate","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.stemcr.2016.07.005","article-title":"The Luteinizing Hormone-Testosterone Pathway Regulates Mouse Spermatogonial Stem Cell Self-Renewal by Suppressing WNT5A Expression in Sertoli Cells","volume":"7","author":"Tanaka","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1365-2605.1993.tb01156.x","article-title":"Histological and Histopathological Evaluation of the Testis","volume":"16","author":"Russell","year":"1993","journal-title":"Int. J. Androl."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhou, Y., and Wang, Y. (2022). Action and Interaction between Retinoic Acid Signaling and Blood-Testis Barrier Function in the Spermatogenesis Cycle. Cells, 11.","DOI":"10.3390\/cells11030352"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1095\/biolreprod.114.118034","article-title":"Riding the Spermatogenic Wave: Profiling Gene Expression Within Neonatal Germ and Sertoli Cells During a Synchronized Initial Wave of Spermatogenesis in Mice","volume":"90","author":"Evans","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1242\/dev.02316","article-title":"The First Round of Mouse Spermatogenesis Is a Distinctive Program That Lacks the Self-Renewing Spermatogonia Stage","volume":"133","author":"Yoshida","year":"2006","journal-title":"Development"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1530\/REP-10-0431","article-title":"Spermatogonial Morphology and Kinetics during Testis Development in Mice: A High-Resolution Light Microscopy Approach","volume":"142","author":"Drumond","year":"2011","journal-title":"Reproduction"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.114.126326","article-title":"Processive Pulses of Retinoic Acid Propel Asynchronous and Continuous Murine Sperm Production","volume":"92","author":"Hogarth","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.116.141770","article-title":"Characterizing the Spermatogonial Response to Retinoic Acid During the Onset of Spermatogenesis and Following Synchronization in the Neonatal Mouse Testis","volume":"95","author":"Agrimson","year":"2016","journal-title":"Biol. Reprod."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Topping, T., and Griswold, M.D. (2022). Global Deletion of ALDH1A1 and ALDH1A2 Genes Does Not Affect Viability but Blocks Spermatogenesis. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.871225"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.2164\/jandrol.112.016832","article-title":"Questions about Spermatogonia Posed and Answered since 2000","volume":"33","author":"Griswold","year":"2012","journal-title":"J. Androl."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1530\/rep.0.1210347","article-title":"Proliferation and Differentiation of Spermatogonial Stem Cells","volume":"121","year":"2001","journal-title":"Reproduction"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cca.2019.07.013","article-title":"The Roles of Retinoic Acid in the Differentiation of Spermatogonia and Spermatogenic Disorders","volume":"497","author":"Li","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/bs.ctdb.2019.04.008","article-title":"Heterogeneous, Dynamic, and Stochastic Nature of Mammalian Spermatogenic Stem Cells","volume":"135","author":"Yoshida","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/aja.1001180211","article-title":"Renewal of Spermatogonia in Man","volume":"118","author":"Clermont","year":"1966","journal-title":"Am. J. Anat."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"145080","DOI":"10.1016\/j.gene.2020.145080","article-title":"Conversion from Spermatogonia to Spermatocytes: Extracellular Cues and Downstream Transcription Network","volume":"764","author":"Xie","year":"2021","journal-title":"Gene"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.semcdb.2016.03.002","article-title":"Spermatogonial Cells: Mouse, Monkey and Man Comparison","volume":"59","author":"Boitani","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"14","DOI":"10.5534\/wjmh.220067","article-title":"Impact of Antioxidant Therapy on Natural Pregnancy Outcomes and Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"41","author":"Agarwal","year":"2023","journal-title":"World J. Mens Health"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Pavuluri, H., Bakhtiary, Z., Panner Selvam, M.K., and Hellstrom, W.J.G. (2024). Oxidative Stress-Associated Male Infertility: Current Diagnostic and Therapeutic Approaches. Medicina, 60.","DOI":"10.3390\/medicina60061008"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/aja.2010.76","article-title":"Leukocytes and Oxidative Stress: Dilemma for Sperm Function and Male Fertility","volume":"13","author":"Henkel","year":"2011","journal-title":"Asian J. Androl."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"296","DOI":"10.5534\/wjmh.190055","article-title":"Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility","volume":"37","author":"Agarwal","year":"2019","journal-title":"World J. Mens Health"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/2090598X.2019.1599624","article-title":"Oxidative Stress and Sperm Function: A Systematic Review on Evaluation and Management","volume":"17","author":"Dutta","year":"2019","journal-title":"Arab J. Urol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.cbi.2014.10.016","article-title":"Free Radicals, Reactive Oxygen Species, Oxidative Stress and Its Classification","volume":"224","author":"Lushchak","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1210\/jc.2007-2616","article-title":"Significance of Mitochondrial Reactive Oxygen Species in the Generation of Oxidative Stress in Spermatozoa","volume":"93","author":"Koppers","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Montjean, D., Beaumont, M., Natiq, A., Louanjli, N., Hazout, A., Miron, P., Liehr, T., Cabry, R., Ratbi, I., and Benkhalifa, M. (2024). Genome and Epigenome Disorders and Male Infertility: Feedback from 15 Years of Clinical and Research Experience. Genes, 15.","DOI":"10.3390\/genes15030377"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.2047-2927.2012.00041.x","article-title":"Prevalence of High DNA Fragmentation Index in Male Partners of Unexplained Infertile Couples","volume":"1","author":"Oleszczuk","year":"2013","journal-title":"Andrology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s10815-012-9801-3","article-title":"Predictive Value of DNA Integrity Analysis in Idiopathic Recurrent Pregnancy Loss Following Spontaneous Conception","volume":"29","author":"Kumar","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1093\/humrep\/den321","article-title":"Sperm DNA Damage Is Associated with an Increased Risk of Pregnancy Loss after IVF and ICSI: Systematic Review and Meta-Analysis","volume":"23","author":"Zini","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wang, Y., Fu, X., and Li, H. (2025). Mechanisms of Oxidative Stress-Induced Sperm Dysfunction. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1520835"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8282387","DOI":"10.1155\/2022\/8282387","article-title":"Glycine Improved Cryopreserved Spermatozoa Quality in Achai Bull","volume":"2022","author":"Nazif","year":"2022","journal-title":"Biomed Res. Int."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/biolre\/ioac148","article-title":"Synchronizing Spermatogenesis in the Mouse","volume":"107","author":"Griswold","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Santos, D., and Payan-Carreira, R. (2019). Retinoic Acid Signaling in Spermatogenesis and Male (in)Fertility. Molecular Signaling in Spermatogenesis and Male Infertility, CRC Press.","DOI":"10.1201\/9780429244216-7"},{"key":"ref_92","first-page":"10","article-title":"The Role of Retinoic Acid (RA) in Spermatogonial Differentiation","volume":"94","author":"Busada","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Beedle, M.T., Hogarth, C.A., and Griswold, M.D. (2017). Role of Retinoic Acid Signaling in the Differentiation of Spermatogonia. The Biology of Mammalian Spermatogonia, Springer.","DOI":"10.1007\/978-1-4939-7505-1_6"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1042\/bst0140936","article-title":"Hypervitaminosis A: Side-Effects of Retinoids","volume":"14","author":"Kistler","year":"1986","journal-title":"Biochem. Soc. Trans."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1046\/j.1460-9568.2003.02765.x","article-title":"Too Much of a Good Thing: Retinoic Acid as an Endogenous Regulator of Neural Differentiation and Exogenous Teratogen","volume":"18","author":"McCaffery","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.immuni.2011.07.002","article-title":"The Role of Retinoic Acid in Tolerance and Immunity","volume":"35","author":"Hall","year":"2011","journal-title":"Immunity"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev-nutr-072610-145127","article-title":"Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism","volume":"31","author":"Ross","year":"2011","journal-title":"Annu. Rev. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1097\/MED.0b013e32836067cf","article-title":"Retinoic Acid Regulation of Male Meiosis","volume":"20","author":"Hogarth","year":"2013","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"11166","DOI":"10.1074\/jbc.RA119.009023","article-title":"The Retinoic Acid Hydroxylase Cyp26a1 Has Minor Effects on Postnatal Vitamin A Homeostasis, but Is Required for Exogenous AtRA Clearance","volume":"294","author":"Zhong","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_100","first-page":"1053","article-title":"How Does Retinoic Acid (RA) Signaling Pathway Regulate Spermatogenesis?","volume":"37","author":"Zhang","year":"2022","journal-title":"Histol. Histopathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.theriogenology.2012.09.001","article-title":"Retinoic Acid Signaling Biomarkers after Treatment with Retinoic Acid and Retinoic Acid Receptor Alpha Antagonist (Ro 41-5253) in Canine Testis: An in Vitro Organ Culture Study","volume":"79","author":"Kasimanickam","year":"2013","journal-title":"Theriogenology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1194\/jlr.M054718","article-title":"Importance of ALDH1A Enzymes in Determining Human Testicular Retinoic Acid Concentrations","volume":"56","author":"Arnold","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"35710","DOI":"10.1038\/srep35710","article-title":"Crystal Structure of Human Aldehyde Dehydrogenase 1A3 Complexed with NAD+ and Retinoic Acid","volume":"6","author":"Moretti","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ydbio.2014.09.016","article-title":"Sex Specific Retinoic Acid Signaling Is Required for the Initiation of Urogenital Sinus Bud Development","volume":"395","author":"Bryant","year":"2014","journal-title":"Dev. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ydbio.2023.03.006","article-title":"In Vitro Induction of Prostate Buds from Murine Urogenital Epithelium in the Absence of Mesenchymal Cells","volume":"498","author":"Uno","year":"2023","journal-title":"Dev. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Bhattacharya, I., Sharma, P., Purohit, S., Kothiyal, S., Das, M., and Banerjee, A. (2022). Recent Update on Retinoic Acid-Driven Initiation of Spermatogonial Differentiation. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.833759"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Huang, Y., and Roig, I. (2023). Genetic Control of Meiosis Surveillance Mechanisms in Mammals. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1127440"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Endo, T., Mikedis, M.M., Nicholls, P.K., Page, D.C., and de Rooij, D.G. (2019). Retinoic Acid and Germ Cell Development in the Ovary and Testis. Biomolecules, 9.","DOI":"10.3390\/biom9120775"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1093\/biolre\/ioae115","article-title":"Temporal Maturation of Sertoli Cells during the Establishment of the Cycle of the Seminiferous Epithelium","volume":"111","author":"Havel","year":"2024","journal-title":"Biol. Reprod."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.mod.2011.12.003","article-title":"Retinoic Acid Metabolism Links the Periodical Differentiation of Germ Cells with the Cycle of Sertoli Cells in Mouse Seminiferous Epithelium","volume":"128","author":"Sugimoto","year":"2012","journal-title":"Mech. Dev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1111\/rda.12756","article-title":"Expression of Retinoic Acid-Metabolizing Enzymes, ALDH1A1, ALDH1A2, ALDH1A3, CYP26A1, CYP26B1 and CYP26C1 in Canine Testis during Post-Natal Development","volume":"51","author":"Kasimanickam","year":"2016","journal-title":"Reprod. Domest. Anim."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/j.1745-7262.2008.00408.x","article-title":"Expression of the Retinoic Acid-Metabolizing Enzymes RALDH2 and CYP26b1 during Mouse Postnatal Testis Development","volume":"10","author":"Wu","year":"2008","journal-title":"Asian J. Androl."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Zuo, Q., Li, D., Zhang, L., Elsayed, A.K., Lian, C., Shi, Q., Zhang, Z., Zhu, R., Wang, Y., and Jin, K. (2015). Study on the Regulatory Mechanism of the Lipid Metabolism Pathways during Chicken Male Germ Cell Differentiation Based on RNA-Seq. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0109469"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"10131","DOI":"10.1038\/srep10131","article-title":"Retinoic Acid Homeostasis through Aldh1a2 and Cyp26a1 Mediates Meiotic Entry in Nile Tilapia (Oreochromis niloticus)","volume":"5","author":"Feng","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.fertnstert.2013.12.053","article-title":"Levels of the Retinoic Acid Synthesizing Enzyme Aldehyde Dehydrogenase-1A2 Are Lower in Testicular Tissue from Men with Infertility","volume":"101","author":"Amory","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1210\/en.2005-0953","article-title":"Retinoic Acid Metabolism and Signaling Pathways in the Adult and Developing Mouse Testis","volume":"147","author":"Vernet","year":"2006","journal-title":"Endocrinology"},{"key":"ref_117","first-page":"34","article-title":"Gonadotropin Regulation of Retinoic Acid Activity in the Testis","volume":"56","author":"Nourashrafeddin","year":"2018","journal-title":"Acta Med. Iran."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1111\/andr.12420","article-title":"Isotretinoin Administration Improves Sperm Production in Men with Infertility from Oligoasthenozoospermia: A Pilot Study","volume":"5","author":"Amory","year":"2017","journal-title":"Andrology"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Liebich, A., Schmid, N., Koupourtidou, C., Herrmann, C., Dietrich, K.G., Welter, H., Ninkovic, J., and Mayerhofer, A. (2022). The Molecular Signature of Human Testicular Peritubular Cells Revealed by Single-Cell Analysis. Cells, 11.","DOI":"10.3390\/cells11223685"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"13856","DOI":"10.1038\/s41598-021-93459-3","article-title":"All Trans Retinoic Acid Alleviates Coronary Stenosis by Regulating Smooth Muscle Cell Function in a Mouse Model of Kawasaki Disease","volume":"11","author":"Suganuma","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/mrd.23323","article-title":"Regulation of Gdnf Expression by Retinoic Acid in Sertoli Cells","volume":"87","author":"Saracino","year":"2020","journal-title":"Mol. Reprod. Dev."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.115.131458","article-title":"ALDH Enzyme Expression Is Independent of the Spermatogenic Cycle, and Their Inhibition Causes Misregulation of Murine Spermatogenic Processes","volume":"94","author":"Kent","year":"2016","journal-title":"Biol. Reprod."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"549","DOI":"10.4103\/aja202156","article-title":"The Role of Retinoic Acid in the Commitment to Meiosis","volume":"23","author":"Gewiss","year":"2021","journal-title":"Asian J. Androl."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.112.105346","article-title":"Turning a Spermatogenic Wave into a Tsunami: Synchronizing Murine Spermatogenesis Using WIN 18,446","volume":"88","author":"Hogarth","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1021\/acschembio.7b00685","article-title":"Structural Basis of ALDH1A2 Inhibition by Irreversible and Reversible Small Molecule Inhibitors","volume":"13","author":"Chen","year":"2018","journal-title":"ACS Chem. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2164\/jandrol.110.010751","article-title":"Suppression of Spermatogenesis by Bisdichloroacetyldiamines Is Mediated by Inhibition of Testicular Retinoic Acid Biosynthesis","volume":"32","author":"Amory","year":"2011","journal-title":"J. Androl."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1095\/biolreprod.110.088575","article-title":"Suppression of Stra8 Expression in the Mouse Gonad by WIN 18,446","volume":"84","author":"Hogarth","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.bcp.2015.03.001","article-title":"Pharmacological Inhibition of ALDH1A in Mice Decreases All-Trans Retinoic Acid Concentrations in a Tissue Specific Manner","volume":"95","author":"Arnold","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/biolre\/ioy200","article-title":"Sources of All-Trans Retinal Oxidation Independent of the Aldehyde Dehydrogenase 1A Isozymes Exist in the Postnatal Testis","volume":"100","author":"Beedle","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"15104","DOI":"10.1074\/jbc.M113.540211","article-title":"Inhibition of Retinoic Acid Biosynthesis by the Bisdichloroacetyldiamine WIN 18,446 Markedly Suppresses Spermatogenesis and Alters Retinoid Metabolism in Mice","volume":"289","author":"Paik","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/mrd.23448","article-title":"STRA8 Induces Transcriptional Changes in Germ Cells during Spermatogonial Development","volume":"88","author":"Gewiss","year":"2021","journal-title":"Mol. Reprod. Dev."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e240432","DOI":"10.1530\/REP-24-0432","article-title":"Regulation of Testosterone Synthesis in Leydig Cells by ClC-2 Chloride Channel","volume":"170","author":"Fu","year":"2025","journal-title":"Reproduction"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"110306","DOI":"10.1016\/j.contraception.2023.110306","article-title":"Return to Fertility, Toxicology, and Transgenerational Impact of Treatment with WIN 18,446, a Potential Male Contraceptive, in Mice","volume":"129","author":"Paik","year":"2024","journal-title":"Contraception"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"114709","DOI":"10.1016\/j.ejmech.2022.114709","article-title":"Male Contraceptive Development: A Medicinal Chemistry Perspective","volume":"243","author":"Norcross","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"112","DOI":"10.9734\/bpi\/rdmmr\/v5\/4390F","article-title":"Insight into the Trends in Male Contraception: An Advanced Study","volume":"Volume 5","author":"Chauhan","year":"2021","journal-title":"Recent Developments in Medicine and Medical Research"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"23","DOI":"10.22159\/ijap.2022v14i2.43941","article-title":"Impending Contraceptives that Might Be a Positive Methodology Towards the Male Contraception","volume":"14","author":"Verma","year":"2022","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1111\/andr.13705","article-title":"Pre-Clinical and Early Clinical Considerations for the Development of Non-Hormonal Contraceptives for Men","volume":"12","author":"Johnston","year":"2024","journal-title":"Andrology"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.pharmthera.2006.02.001","article-title":"Pharmacological Treatment of Alcohol Dependence: Target Symptoms and Target Mechanisms","volume":"111","author":"Heilig","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.tem.2011.01.001","article-title":"Inhibiting Vitamin A Metabolism as an Approach to Male Contraception","volume":"22","author":"Hogarth","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e2381","DOI":"10.1210\/clinem\/dgab034","article-title":"Update on Novel Hormonal and Nonhormonal Male Contraceptive Development","volume":"106","author":"Long","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"26334941221138323","DOI":"10.1177\/26334941221138323","article-title":"Emerging Concepts in Male Contraception: A Narrative Review of Novel, Hormonal and Non-Hormonal Options","volume":"17","author":"Service","year":"2023","journal-title":"Ther. Adv. Reprod. Health"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12610-023-00204-z","article-title":"Male Contraception: Narrative Review of Ongoing Research","volume":"33","author":"Louwagie","year":"2023","journal-title":"Basic Clin. Androl."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"24","DOI":"10.38094\/jlbsr502115","article-title":"Recent Developments in Promising Hormonal and Non- Hormonal Male Contraceptives: A Review","volume":"5","author":"Yahya","year":"2024","journal-title":"J. Life Bio Sci. Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"116801","DOI":"10.1016\/j.taap.2023.116801","article-title":"Determination of Pharmacological Inhibition of ALDH2 by Ethanol Clearance in Mice","volume":"483","author":"Haenisch","year":"2024","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1111\/andr.13652","article-title":"Emerging Approaches to Male Contraception","volume":"12","author":"Yan","year":"2024","journal-title":"Andrology"},{"key":"ref_146","first-page":"603","article-title":"Male Contraception","volume":"93","author":"Abbe","year":"2020","journal-title":"Yale J. Biol. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/j.fertnstert.2021.03.047","article-title":"Emerging Approaches to Male Contraception","volume":"115","author":"Thirumalai","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_148","unstructured":"Amory, J.K. (2023). What Are the Current Approaches to Non-Hormonal Male Contraception?. Handbook of Andrology, American Society of Andrology."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/nrg2723","article-title":"Genetics of Mammalian Meiosis: Regulation, Dynamics and Impact on Fertility","volume":"11","author":"Handel","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"101282","DOI":"10.1016\/j.mam.2024.101282","article-title":"Mechanisms of Meiosis Initiation and Meiotic Prophase Progression during Spermatogenesis","volume":"97","author":"Ishiguro","year":"2024","journal-title":"Mol. Asp. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.coemr.2020.05.001","article-title":"Regulation of Meiosis Initiation in the Mammalian Testis: Novel Aspects","volume":"14","author":"Edelsztein","year":"2020","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Koubova, J., Hu, Y.C., Bhattacharyya, T., Soh, Y.Q.S., Gill, M.E., Goodheart, M.L., Hogarth, C.A., Griswold, M.D., and Page, D.C. (2014). Retinoic Acid Activates Two Pathways Required for Meiosis in Mice. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004541"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1530\/REP-22-0286","article-title":"Conserved H3K27me3-Associated Chromatin Remodelling Allows STRA8 but Not MEIOSIN Expression in Mammalian Germ Cells","volume":"165","author":"Ishihara","year":"2023","journal-title":"Reproduction"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"dev201638","DOI":"10.1242\/dev.201638","article-title":"Retinoic Acid Is Dispensable for Meiotic Initiation but Required for Spermiogenesis in the Mammalian Testis","volume":"150","author":"Kirsanov","year":"2023","journal-title":"Development"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1093\/biolre\/ioad010","article-title":"Differential Responsiveness of Spermatogonia to Retinoic Acid Dictates Precocious Differentiation but Not Meiotic Entry during Steady-State Spermatogenesis","volume":"108","author":"Johnson","year":"2023","journal-title":"Biol. Reprod."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"16582","DOI":"10.1073\/pnas.1214936109","article-title":"Retinoic Acid Induces Sertoli Cell Paracrine Signals for Spermatogonia Differentiation but Cell Autonomously Drives Spermatocyte Meiosis","volume":"109","author":"Raverdeau","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.1242\/dev.02031","article-title":"Retinoic Acid-Dependent Eye Morphogenesis Is Orchestrated by Neural Crest Cells","volume":"132","author":"Matt","year":"2005","journal-title":"Development"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"14036","DOI":"10.1073\/pnas.2336223100","article-title":"A Newborn Lethal Defect Due to Inactivation of Retinaldehyde Dehydrogenase Type 3 Is Prevented by Maternal Retinoic Acid Treatment","volume":"100","author":"Matt","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","first-page":"198","article-title":"Alcohol and Aldehyde Dehydrogenases: Retinoid Metabolic Effects in Mouse Knockout Models","volume":"1821","author":"Kumar","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1093\/biolre\/ioy031","article-title":"Leydig Cell Genes Change Their Expression and Association with Polysomes in a Stage-Specific Manner in the Adult Mouse Testis","volume":"98","author":"Jauregui","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Zhong, O., Liao, B., Wang, J., Liu, K., Lei, X., and Hu, L. (2022). Effects of Sleep Disorders and Circadian Rhythm Changes on Male Reproductive Health: A Systematic Review and Meta-Analysis. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.913369"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Hod\u017ei\u0107, A., Ristanovi\u0107, M., Zorn, B., Tuli\u0107, C., Maver, A., Novakovi\u0107, I., and Peterlin, B. (2013). Genetic Variation in Circadian Rhythm Genes CLOCK and ARNTL as Risk Factor for Male Infertility. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059220"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1093\/humrep\/deaa101","article-title":"Adverse Effects of Circadian Desynchrony on the Male Reproductive System: An Epidemiological and Experimental Study","volume":"35","author":"Liu","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.pbiomolbio.2013.01.003","article-title":"Circadian Regulation of Reproduction: From Gamete to Offspring","volume":"113","author":"Boden","year":"2013","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/mrd.22968","article-title":"Cry1 Deficiency Leads to Testicular Dysfunction and Altered Expression of Genes Involved in Cell Communication, Chromatin Reorganization, Spermatogenesis, and Immune Response in Mouse Testis","volume":"85","author":"Li","year":"2018","journal-title":"Mol. Reprod. Dev."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10815-021-02375-y","article-title":"Altered Circadian Clock Gene Expression in the Sperm of Infertile Men with Asthenozoospermia","volume":"39","author":"Zhang","year":"2022","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Li, T., Bai, Y., Jiang, Y., Jiang, K., Tian, Y., Gu, J., and Sun, F. (2022). The Potential Impacts of Circadian Rhythm Disturbances on Male Fertility. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1001316"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"64","DOI":"10.5213\/inj.2011.15.2.64","article-title":"Circadian Rhythms in Urinary Functions: Possible Roles of Circadian Clocks?","volume":"15","author":"Noh","year":"2011","journal-title":"Int. Neurourol. J."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Walker, W.H., Bumgarner, J.R., Walton, J.C., Liu, J.A., Mel\u00e9ndez-Fern\u00e1ndez, O.H., Nelson, R.J., and Devries, A.C. (2020). Light Pollution and Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249360"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1161\/CIRCRESAHA.116.308034","article-title":"Circadian Influence on Metabolism and Inflammation in Atherosclerosis","volume":"119","author":"McAlpine","year":"2016","journal-title":"Circ. Res."},{"key":"ref_171","first-page":"799","article-title":"Regulation of Reproduction by the Circadian Rhythms","volume":"68","author":"Zhang","year":"2016","journal-title":"Sheng Li Xue Bao"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"nwae456","DOI":"10.1093\/nsr\/nwae456","article-title":"The Circadian Clock Orchestrates Spermatogonial Differentiation and Fertilization by Regulating Retinoic Acid Signaling in Vertebrates","volume":"12","author":"Liu","year":"2025","journal-title":"Natl. Sci. Rev."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Morrison, H. (2021). Aldehyde Dehydrogenase. Enzyme Active Sites and their Reaction Mechanisms, Elsevier.","DOI":"10.1016\/B978-0-12-821067-3.00005-2"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/978-981-13-6260-6_3","article-title":"ALDH2 and Cardiovascular Disease","volume":"1193","author":"Chen","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.rvsc.2021.03.024","article-title":"The Role of Endogenous Antioxidants in Male Animal Fertility","volume":"136","author":"Gibb","year":"2021","journal-title":"Res. Vet. Sci."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.urology.2018.09.029","article-title":"Racial and Sociodemographic Differences of Semen Parameters Among US Men Undergoing a Semen Analysis","volume":"123","author":"Glazer","year":"2019","journal-title":"Urology"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.urology.2017.03.064","article-title":"Racial Variation in Semen Quality at Fertility Evaluation","volume":"106","author":"Khandwala","year":"2017","journal-title":"Urology"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.cotox.2017.10.003","article-title":"Role of Cytochrome P450s in the Generation and Metabolism of Reactive Oxygen Species","volume":"7","author":"Veith","year":"2018","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1365-2605.1980.tb00127.x","article-title":"Testicular and Epididymal Aldehyde Dehydrogenase in Rodents: Modulation by Ethanol and Disulfiram","volume":"3","author":"Andrology","year":"1980","journal-title":"Int. J. Androl."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Na, H.-K., and Lee, J.Y. (2017). Molecular Basis of Alcohol-Related Gastric and Colon Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061116"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"574","DOI":"10.2486\/indhealth.45.574","article-title":"Reproductive Toxicity of Ethylene Glycol Monoethyl Ether in Aldh2 Knockout Mice","volume":"45","author":"Wang","year":"2007","journal-title":"Ind. Health"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1095\/biolreprod.116.140509","article-title":"Aldehyde Dehydrogenase Plays a Pivotal Role in the Maintenance of Stallion Sperm Motility","volume":"94","author":"Gibb","year":"2016","journal-title":"Biol. Reprod."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Taoto, C., Tangsrisakda, N., Thukhammee, W., Phetcharaburanin, J., Iamsaard, S., and Tanphaichitr, N. (2024). Rats Orally Administered with Ethyl Alcohol for a Prolonged Time Show Histopathology of the Epididymis and Seminal Vesicle Together with Changes in the Luminal Metabolite Composition. Biomedicines, 12.","DOI":"10.3390\/biomedicines12051010"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"114397","DOI":"10.1016\/j.yexcr.2024.114397","article-title":"ALDH2 Plays a Role in Spermatogenesis and Male Fertility by Regulating Oxidative Stress in Mice","volume":"444","author":"Lv","year":"2025","journal-title":"Exp. Cell Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.theriogenology.2018.04.025","article-title":"Quantitative Proteomic Profiling Indicates the Difference in Reproductive Efficiency between Meishan and Duroc Boar Spermatozoa","volume":"116","author":"Xinhong","year":"2018","journal-title":"Theriogenology"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1097\/JU.0000000000002682","article-title":"ALDH2 Expression, Alcohol Intake, and Semen Parameters Among East Asian Men","volume":"208","author":"Greenberg","year":"2022","journal-title":"J. Urol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"e172","DOI":"10.1097\/01.JU.0001109764.27496.08.08","article-title":"PD06-08 Exploring the Effects of Aldh2 Alcohol Intolerance and Alcohol Consumption on Male Fertility","volume":"213","author":"Le","year":"2025","journal-title":"J. Urol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1080\/19396368.2022.2057257","article-title":"High Throughput Deep Proteomic Analysis of Seminal Plasma from Stallions with Contrasting Semen Quality","volume":"68","author":"Talluri","year":"2022","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1002\/j.1939-4640.2001.tb02229.x","article-title":"The Role of Glucose in Supporting Motility and Capacitation in Human Spermatozoa","volume":"22","author":"Williams","year":"2001","journal-title":"J. Androl."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.114.118539","article-title":"The Paradoxical Relationship between Stallion Fertility and Oxidative Stress","volume":"91","author":"Gibb","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.theriogenology.2010.02.029","article-title":"Inhibition of the Mitochondrial Permeability Transition Pore Reduces \u201cApoptosis like\u201d Changes during Cryopreservation of Stallion Spermatozoa","volume":"74","author":"Ferrusola","year":"2010","journal-title":"Theriogenology"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.112.102020","article-title":"Sperm Motility Is Lost in Vitro as a Consequence of Mitochondrial Free Radical Production and the Generation of Electrophilic Aldehydes but Can Be Significantly Rescued by the Presence of Nucleophilic Thiols","volume":"87","author":"Aitken","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.taap.2004.08.023","article-title":"Toxicity and Detoxification of Lipid-Derived Aldehydes in Cultured Retinal Pigmented Epithelial Cells","volume":"204","author":"Choudhary","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.anireprosci.2013.12.007","article-title":"Thiol-Disulfide Proteins of Stallion Epididymal Spermatozoa","volume":"145","author":"Dias","year":"2014","journal-title":"Anim. Reprod. Sci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"33048","DOI":"10.1074\/jbc.M112.366690","article-title":"Electrophilic Aldehydes Generated by Sperm Metabolism Activate Mitochondrial Reactive Oxygen Species Generation and Apoptosis by Targeting Succinate Dehydrogenase","volume":"287","author":"Aitken","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/molehr\/gav014","article-title":"Oxidative Stress and Human Spermatozoa: Diagnostic and Functional Significance of Aldehydes Generated as a Result of Lipid Peroxidation","volume":"21","author":"Moazamian","year":"2015","journal-title":"Mol. Hum. Reprod."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1021\/tx0501839","article-title":"Inhibition of Human Mitochondrial Aldehyde Dehydrogenase by 4-Hydroxynon-2-Enal and 4-Oxonon-2-Enal","volume":"19","author":"Doorn","year":"2006","journal-title":"Chem. Res. Toxicol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.redox.2014.12.011","article-title":"Role of Lipid Peroxidation Derived 4-Hydroxynonenal (4-HNE) in Cancer: Focusing on Mitochondria","volume":"4","author":"Zhong","year":"2015","journal-title":"Redox Biol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"103765","DOI":"10.1016\/j.jprot.2020.103765","article-title":"Proteomic Profiling of Stallion Spermatozoa Suggests Changes in Sperm Metabolism and Compromised Redox Regulation after Cryopreservation","volume":"221","author":"Tapiad","year":"2020","journal-title":"J. Proteom."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Davila, M.P., Mu\u00f1oz, P.M., Tapia, J.A., Ferrusola, C.O., Da Silva, C.C.B., and Pe\u00f1a, F.J. (2015). Inhibition of Mitochondrial Complex I Leads to Decreased Motility and Membrane Integrity Related to Increased Hydrogen Peroxide and Reduced ATP Production, While the Inhibition of Glycolysis Has Less Impact on Sperm Motility. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138777"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1093\/biolre\/ioy241","article-title":"Depletion of Thiols Leads to Redox Deregulation, Production of 4-Hydroxinonenal and Sperm Senescence: A Possible Role for GSH Regulation in Spermatozoa","volume":"100","author":"Tapia","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jevs.2018.08.004","article-title":"Activator of Mitochondrial Aldehyde Dehydrogenase (Alda-1) Could Enhance Quality of Equine Cooled Semen by Ameliorating Loss of Mitochondrial Function Over Time","volume":"70","author":"Akbarinejad","year":"2018","journal-title":"J. Equine Vet. Sci."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Karanwal, S., Pal, A., Chera, J.S., Batra, V., Kumaresan, A., Datta, T.K., and Kumar, R. (2023). Identification of Protein Candidates in Spermatozoa of Water Buffalo (Bubalus bubalis) Bulls Helps in Predicting Their Fertility Status. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1119220"},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Badrhan, S., Karanwal, S., Pal, A., Chera, J.S., Chauhan, V., Patel, A., Bhakat, M., Datta, T.K., and Kumar, R. (2024). Differential Protein Repertoires Related to Sperm Function Identified in Extracellular Vesicles (EVs) in Seminal Plasma of Distinct Fertility Buffalo (Bubalus bubalis) Bulls. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1400323"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3390\/cimb44010031","article-title":"Characterization of the Testis-Specific Angiotensin Converting Enzyme (TACE)-Interactome during Bovine Sperm Capacitation","volume":"44","author":"Ojaghi","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Aitken, R.J., Drevet, J.R., Moazamian, A., and Gharagozloo, P. (2022). Male Infertility and Oxidative Stress: A Focus on the Underlying Mechanisms. Antioxidants, 11.","DOI":"10.3390\/antiox11020306"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"113967","DOI":"10.1016\/j.fct.2023.113967","article-title":"Loss of Atg5 in Sertoli Cells Enhances the Susceptibility of Cadmium-Impaired Testicular Spermatogenesis in Mice","volume":"179","author":"Xiong","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2022.01.006","article-title":"3-Monochloropropane-1,2-Diol Causes Spermatogenesis Failure in Male Rats via Sertoli Cell Dysfunction but Not Testosterone Reduction","volume":"360","author":"Xing","year":"2022","journal-title":"Toxicol. Lett."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s00204-014-1192-z","article-title":"Assessment of the Reproductive Toxicity of Inhalation Exposure to Ethyl Tertiary Butyl Ether in Male Mice with Normal, Low Active and Inactive ALDH2","volume":"88","author":"Weng","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1124\/jpet.121.000614","article-title":"A Chemoproteomics Approach to Determine the Mechanism of Testicular Toxicity for the Bruton\u2019s Tyrosine Kinase Inhibitor CC-292","volume":"379","author":"Labenski","year":"2021","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1177\/0192623316672744","article-title":"Impact of Age on the Male Reproductive System from the Pathologist\u2019s Perspective","volume":"45","author":"Picut","year":"2017","journal-title":"Toxicol. Pathol."},{"key":"ref_212","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_213","doi-asserted-by":"crossref","unstructured":"Crafa, A., Cannarella, R., Calogero, A.E., Gunes, S., and Agarwal, A. (2024). Behind the Genetics: The Role of Epigenetics in Infertility-Related Testicular Dysfunction. Life, 14.","DOI":"10.3390\/life14070803"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"108898","DOI":"10.1016\/j.envint.2024.108898","article-title":"Advances in Immunology of Male Reproductive Toxicity Induced by Common Environmental Pollutants","volume":"190","author":"Li","year":"2024","journal-title":"Environ. Int."},{"key":"ref_215","first-page":"1067","article-title":"Testicular Macrophage Origin","volume":"18","author":"Fehervari","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41422-018-0099-2","article-title":"The Adult Human Testis Transcriptional Cell Atlas","volume":"28","author":"Guo","year":"2018","journal-title":"Cell Res."},{"key":"ref_217","first-page":"446","article-title":"Testicular Inflammation in Male Reproductive System","volume":"4","author":"Yadav","year":"2024","journal-title":"Open Explor."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1134\/S002689332204015X","article-title":"Deletion of Aldh4a1 Leads to Impaired Sperm Maturation in Mice","volume":"56","author":"Xiao","year":"2022","journal-title":"Mol. Biol."},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Baldi, E., Tamburrino, L., Marchiani, S., Breitbart, H., and Grinshtein, E. (2023). Mechanisms That Protect Mammalian Sperm from the Spontaneous Acrosome Reaction. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242317005"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"e13308","DOI":"10.1111\/acel.13308","article-title":"Incomplete Proline Catabolism Drives Premature Sperm Aging","volume":"20","author":"Yen","year":"2021","journal-title":"Aging Cell"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"e52899","DOI":"10.7554\/eLife.52899","article-title":"Loss of Flavin Adenine Dinucleotide (FAD) Impairs Sperm Function and Male Reproductive Advantage in C. Elegans","volume":"9","author":"Yen","year":"2020","journal-title":"Elife"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"100908","DOI":"10.1016\/j.isci.2020.100908","article-title":"Tet1 Deficiency Leads to Premature Reproductive Aging by Reducing Spermatogonia Stem Cells and Germ Cell Differentiation","volume":"23","author":"Huang","year":"2020","journal-title":"iScience"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/andr.12362","article-title":"Spermatozoa from Males with Reduced Fecundity Exhibit Differential DNA Methylation Patterns","volume":"5","author":"Laqqan","year":"2017","journal-title":"Andrology"},{"key":"ref_224","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_225","doi-asserted-by":"crossref","unstructured":"Pini, T., Nixon, B., Karr, T.L., Teperino, R., Sanz-Moreno, A., Silva-Buttkus, P.d., T\u00fcttelmann, F., Kliesch, S., Gailus-Durner, V., and Fuchs, H. (2025). Towards a Kingdom of Reproductive Life\u2014The Core Sperm Proteome. bioRxiv.","DOI":"10.1101\/2025.03.06.641666"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.biochi.2020.09.016","article-title":"Impact of Missense Mutations in the ALDH7A1 Gene on Enzyme Structure and Catalytic Function","volume":"183","author":"Korasick","year":"2021","journal-title":"Biochimie"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.euros.2023.06.004","article-title":"Proteomic Analysis of Testicular Interstitial Fluid in Men with Azoospermia","volume":"54","author":"Huang","year":"2023","journal-title":"Eur. Urol. Open Sci."},{"key":"ref_228","doi-asserted-by":"crossref","unstructured":"F\u00e1brega-Guer\u00e9n, F., Andrade, J.C., Z\u00fa\u00f1iga-C\u00f3ndor, M., Morales, P., G\u00f3mez-Silva, B., and Z\u00fa\u00f1iga, L.M. (2025). Mating Increases CHST10 Activity in Rat Oviductal Mucosa to Induce the Synthesis of HNK-1 Glycoproteins: Possible Role in Sperm\u2013Oviduct Interactions. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073309"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/humrep\/der423","article-title":"The Continued Presence of Stem Cells and Oogonia in the Adult Mammalian Ovary","volume":"27","author":"Bhartiya","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/rmb2.12220","article-title":"Biology and Manipulation Technologies of Male Germline Stem Cells in Mammals","volume":"17","author":"Takashima","year":"2018","journal-title":"Reprod. Med. Biol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.cell.2004.11.011","article-title":"Generation of Pluripotent Stem Cells from Neonatal Mouse Testis","volume":"119","author":"Inoue","year":"2004","journal-title":"Cell"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/nature04697","article-title":"Pluripotency of Spermatogonial Stem Cells from Adult Mouse Testis","volume":"440","author":"Guan","year":"2006","journal-title":"Nature"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1002\/stem.669","article-title":"Concise Review: Challenging the Pluripotency of Human Testis-Derived ESC-like Cells","volume":"29","author":"Tapia","year":"2011","journal-title":"Stem Cells"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/molehr\/gat076","article-title":"Mesenchymal Origin of Multipotent Human Testis-Derived Stem Cells in Human Testicular Cell Cultures","volume":"20","author":"Chikhovskaya","year":"2014","journal-title":"Mol. Hum. Reprod."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12958-015-0121-1","article-title":"Very Small Embryonic-like Stem Cells (VSELs) Detected in Azoospermic Testicular Biopsies of Adult Survivors of Childhood Cancer","volume":"13","author":"Kurkure","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/j.1432-0436.2008.00268.x","article-title":"Putative Stem Cells with an Embryonic Character Isolated from the Ovarian Surface Epithelium of Women with No Naturally Present Follicles and Oocytes","volume":"76","author":"Zech","year":"2008","journal-title":"Differentiation"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1177\/1933719115576727","article-title":"Mouse Ovarian Very Small Embryonic-like Stem Cells Resist Chemotherapy and Retain Ability to Initiate Oocyte-Specific Differentiation","volume":"22","author":"Sriraman","year":"2015","journal-title":"Reprod. Sci."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12958-015-0031-2","article-title":"Chemoablated Mouse Seminiferous Tubular Cells Enriched for Very Small Embryonic-like Stem Cells Undergo Spontaneous Spermatogenesis in Vitro","volume":"13","author":"Anand","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1477-7827-12-114","article-title":"Making Gametes from Pluripotent Stem Cells\u2014A Promising Role for Very Small Embryonic-like Stem Cells","volume":"12","author":"Bhartiya","year":"2014","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/humupd\/dmw030","article-title":"Endogenous, Very Small Embryonic-like Stem Cells: Critical Review, Therapeutic Potential and a Look Ahead","volume":"23","author":"Bhartiya","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1111\/1471-0528.15638","article-title":"What Can Stem Cell Technology Offer to IVF Patients?","volume":"126","author":"Ilic","year":"2019","journal-title":"BJOG"},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Lord, T., and Oatley, J.M. (2017). Regulation of Spermatogonial Stem Cell Maintenance and Self-Renewal. Biology of Mammalian Spermatogonia, Springer.","DOI":"10.1007\/978-1-4939-7505-1_5"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1001\/jamaoncol.2016.1002","article-title":"Use of Very Small Embryonic-like Stem Cells to Avoid Legal, Ethical, and Safety Issues Associated with Oncofertility","volume":"2","author":"Bhartiya","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13048-015-0199-2","article-title":"VSELs May Obviate Cryobanking of Gonadal Tissue in Cancer Patients for Fertility Preservation","volume":"8","author":"Bhartiya","year":"2015","journal-title":"J. Ovarian Res."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.devcel.2020.01.014","article-title":"Metabolic Changes Accompanying Spermatogonial Stem Cell Differentiation","volume":"52","author":"Lord","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4103\/ctm.ctm_69_16","article-title":"Stemness-Related Markers in Cancer","volume":"3","author":"Zhao","year":"2017","journal-title":"Cancer Transl. Med."},{"key":"ref_247","first-page":"1","article-title":"Enrichment of Mouse Spermatogonial Stem Cells Based on Aldehyde Dehydrogenase Activity","volume":"89","author":"Mori","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1155\/2008\/536020","article-title":"The Application of Biomarkers of Spermatogonial Stem Cells for Restoring Male Fertility","volume":"24","author":"Ebata","year":"2008","journal-title":"Dis. Markers"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1002\/stem.2612","article-title":"High Aldehyde Dehydrogenase Activity Identifies a Subset of Human Mesenchymal Stromal Cells with Vascular Regenerative Potential","volume":"35","author":"Sherman","year":"2017","journal-title":"Stem Cells"},{"key":"ref_250","doi-asserted-by":"crossref","unstructured":"Xu, Y., and Xie, J. (2021). Etomoxir Regulates the Differentiation of Male Germ Cells by Specifically Reducing H3K27ac Level. BMC Dev. Biol., 21.","DOI":"10.1186\/s12861-020-00237-x"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40246-020-00291-3","article-title":"Aldh1l2 Knockout Mouse Metabolomics Links the Loss of the Mitochondrial Folate Enzyme to Deregulation of a Lipid Metabolism Observed in Rare Human Disorder","volume":"14","author":"Krupenko","year":"2020","journal-title":"Hum. Genom."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cryobiol.2022.03.006","article-title":"The Effect of Betaine for Mouse Sperm Cryopreservation","volume":"106","author":"Mori","year":"2022","journal-title":"Cryobiology"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/4\/617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:37:38Z","timestamp":1776163058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/4\/617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":252,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ph19040617"],"URL":"https:\/\/doi.org\/10.3390\/ph19040617","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]}}}