{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T10:44:06Z","timestamp":1783248246610,"version":"3.54.6"},"reference-count":79,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-165962"],"award-info":[{"award-number":["PJT-165962"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-191704"],"award-info":[{"award-number":["PJT-191704"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Institute-MUHC Desjardins Studentship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Infertility is a growing global health concern, with male infertility contributing to nearly half of all cases. While conventional semen analysis often overlooks functional impairments, oxidative stress has emerged as a key factor affecting sperm quality. Notably, oxidative stress is elevated in obesity, a rising epidemic affecting more than 1 in 8 people worldwide. This study examines the role of deoxycholic acid (DCA), a secondary bile acid that is elevated in obesity, and its potential to induce oxidative stress and impair sperm function. Semen samples from healthy donors were incubated with DCA, and its effects on sperm motility, viability, capacitation, and oxidative stress markers were assessed. Sperm motility and viability were evaluated using computer-assisted semen analysis (CASA) and hypo-osmotic swelling (HOS) tests, while sperm capacitation was measured via tyrosine phosphorylation (P-Tyr) and acrosome reaction (AR). Oxidative stress markers were quantified using flow cytometry. While progressive motility and viability remained unchanged, DCA reduced hyperactive motility, P-Tyr, and acrosome reaction and increased oxidative stress markers in spermatozoa. These findings suggest that secondary bile acids can disrupt sperm function through oxidative mechanisms, affecting non-conventional semen parameters that may go undetected in standard analyses. This underscores the gut-testis axis\u2019s role in male infertility and highlights the need for more comprehensive diagnostics and targeted therapies.<\/jats:p>","DOI":"10.3390\/antiox14111271","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"1271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deoxycholic Acid Impairs Human Sperm Quality and Function Through Oxidative Stress-Driven Damage"],"prefix":"10.3390","volume":"14","author":[{"given":"Steven","family":"Serafini","sequence":"first","affiliation":[{"name":"Department of Medicine, Experimental Medicine Division, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Department of Surgery, Urology Division, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"The Research Institute, McGill University Health Centre, 1001 Decarie Blvd, Room EM02312, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Pranov","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, McGill University, Montr\u00e9al, QC H3A 0C7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaya","family":"Timova Bauer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, QC H3G 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3251-3897","authenticated-orcid":false,"given":"Chika","family":"Onochie","sequence":"additional","affiliation":[{"name":"Department of Medicine, Experimental Medicine Division, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Department of Surgery, Urology Division, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, QC H3G 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8884-1274","authenticated-orcid":false,"given":"Cristian","family":"O\u2019Flaherty","sequence":"additional","affiliation":[{"name":"Department of Medicine, Experimental Medicine Division, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Department of Surgery, Urology Division, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"The Research Institute, McGill University Health Centre, 1001 Decarie Blvd, Room EM02312, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Department of Anatomy and Cell Biology, McGill University, Montr\u00e9al, QC H3A 0C7, Canada"},{"name":"Department of Pharmacology and Therapeutics, McGill University, Montr\u00e9al, QC H3G 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","unstructured":"Collins, M.E. (2019). The impact of infertility on daily occupations and roles. J. Reprod. Infertil., 20."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cox, C., Thoma, M., Tchangalova, N., Mburu, G., Bornstein, M., Johnson, C., and Kiarie, J. (2022). Infertility prevalence and the methods of estimation from 1990 to 2021: A systematic review and meta-analysis. Hum. Reprod. Open, 2022.","DOI":"10.1093\/hropen\/hoac051"},{"key":"ref_3","unstructured":"World Health Organization (2023). Infertility Prevalence Estimates, 1990\u20132021, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1177\/1933719111398148","article-title":"Human male infertility: A complex multifactorial phenotype","volume":"18","author":"Singh","year":"2011","journal-title":"Reprod. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Longo, V., Forleo, A., Provenzano, S.P., Coppola, L., Zara, V., Ferramosca, A., Siciliano, P., and Capone, S. (2019). Seminal VOCs Analysis Investigating Sperm Quality Decline\u2014New Studies to Improve Male Fertility Contrasting Population Ageing. Ambient Assisted Living: Italian Forum 2018, Springer.","DOI":"10.1007\/978-3-030-05921-7_40"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Aitken, R.J. (2013). Falling sperm counts twenty years on: Where are we now?. Asian J. Androl., 15.","DOI":"10.1038\/aja.2012.167"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sahu, A., and Pajai, S. (2023). The impact of obesity on reproductive health and pregnancy outcomes. Cureus, 15.","DOI":"10.7759\/cureus.48882"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3109\/14647273.2015.1070438","article-title":"Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility","volume":"18","author":"Davidson","year":"2015","journal-title":"Hum. Fertil."},{"key":"ref_9","unstructured":"Feingold, K.R., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., Dungan, K., and Hofland, J. (2000). Clinical problems caused by obesity. Endotext, MDText.com, Inc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.3892\/mmr.2016.5712","article-title":"Curcumin ameliorates high-fat diet-induced spermatogenesis dysfunction","volume":"14","author":"Mu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mu, Y., Yan, W.-J., Yin, T.-L., Zhang, Y., Li, J., and Yang, J. (2017). Diet-induced obesity impairs spermatogenesis: A potential role for autophagy. Sci. Rep., 7.","DOI":"10.1038\/srep43475"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3923\/ijp.2007.27.33","article-title":"Effect of fixed oil of Nigella sativa on male fertility in normal and hyperlipidemic rats","volume":"3","author":"Bashandy","year":"2007","journal-title":"Int. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Saez Lancellotti, T.E., Boarelli, P.V., Monclus, M.A., Cabrillana, M.E., Clementi, M.A., Esp\u00ednola, L.S., Cid Barria, J.L., Vincenti, A.E., Santi, A.G., and Forn\u00e9s, M.W. (2010). Hypercholesterolemia impaired sperm functionality in rabbits. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013457"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Saez Lancellotti, T.E., Boarelli, P.V., Romero, A.A., Funes, A.K., Cid-Barria, M., Cabrillana, M.E., Monclus, M.A., Sim\u00f3n, L., Vicenti, A.E., and Forn\u00e9s, M.W. (2013). Semen quality and sperm function loss by hypercholesterolemic diet was recovered by addition of olive oil to diet in rabbit. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0052386"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.fertnstert.2003.06.026","article-title":"Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index","volume":"81","author":"Aziz","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, X., Gong, L., and Xu, J. (2012, January 28\u201330). Probiotics attenuate sperm damage induced by oxidative stress in rats. Proceedings of the 2012 International Conference on Biomedical Engineering and Biotechnology, Macau, China.","DOI":"10.1109\/iCBEB.2012.314"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/andr.12182","article-title":"A high-fat diet negatively affects rat sperm mitochondrial respiration","volume":"4","author":"Ferramosca","year":"2016","journal-title":"Andrology"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Leisegang, K., Sengupta, P., Agarwal, A., and Henkel, R. (2021). Obesity and male infertility: Mechanisms and management. Andrologia, 53.","DOI":"10.1111\/and.13617"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Pushpendra, A., and Jain, G. (2015). Hyper-lipidemia and male fertility: A critical review of literature. Andrology, 4.","DOI":"10.4172\/2167-0250.1000141"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1439-0272.2012.01272.x","article-title":"Melatonin prevents testicular damage in hyperlipidaemic mice","volume":"44","author":"Zhang","year":"2012","journal-title":"Andrologia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1095\/biolreprod.107.061242","article-title":"Peroxisomes in human and mouse testis: Differential expression of peroxisomal proteins in germ cells and distinct somatic cell types of the testis","volume":"77","author":"Nenicu","year":"2007","journal-title":"Biol. Reprod."},{"key":"ref_22","first-page":"289","article-title":"Biological basis for human capacitation\u2014Revisited","volume":"23","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.freeradbiomed.2006.04.027","article-title":"Positive role of reactive oxygen species in mammalian sperm capacitation: Triggering and modulation of phosphorylation events","volume":"41","author":"Gagnon","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1089\/ars.2021.0117","article-title":"Redox regulation to modulate phosphorylation events in human spermatozoa","volume":"37","author":"Serafini","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tamburrino, L., Marchiani, S., Muratori, M., Luconi, M., and Baldi, E. (2020). Progesterone, spermatozoa and reproduction: An updated review. Mol. Cell. Endocrinol., 516.","DOI":"10.1016\/j.mce.2020.110952"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0891-5849(94)00169-K","article-title":"Capacitation-associated production of superoxide anion by human spermatozoa","volume":"18","author":"Gagnon","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1365-2605.1993.tb01177.x","article-title":"Reactive oxygen species in semen of infertile patients: Levels of superoxide dismutase-and catalase-like activities in seminal plasma and spermatozoa","volume":"16","author":"Zini","year":"1993","journal-title":"Int. J. Androl."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/molehr\/3.3.203","article-title":"Biochemistry of the induction and prevention of lipoperoxidative damage in human spermatozoa","volume":"3","author":"Storey","year":"1997","journal-title":"Mol. Hum. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1095\/biolreprod59.5.1037","article-title":"Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa","volume":"59","author":"Aitken","year":"1998","journal-title":"Biol. Reprod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/j.1939-4640.1995.tb00566.x","article-title":"Role of oxidative stress and antioxidants in male infertility","volume":"16","author":"Sikka","year":"1995","journal-title":"J. Androl."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., and Bitto, A. (2017). Oxidative stress: Harms and benefits for human health. Oxidative Med. Cell. Longev., 2017.","DOI":"10.1155\/2017\/8416763"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1038\/s41430-020-0607-6","article-title":"Profile of the gut microbiota of adults with obesity: A systematic review","volume":"74","author":"Crovesy","year":"2020","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15718","DOI":"10.1073\/pnas.0407076101","article-title":"The gut microbiota as an environmental factor that regulates fat storage","volume":"101","author":"Ding","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.repbio.2018.01.010","article-title":"Relationships between bacteriospermia, DNA integrity, nuclear protamine alteration, sperm quality and ICSI outcome","volume":"18","author":"Zeyad","year":"2018","journal-title":"Reprod. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ricci, S., De Giorgi, S., Lazzeri, E., Luddi, A., Rossi, S., Piomboni, P., De Leo, V., and Pozzi, G. (2018). Impact of asymptomatic genital tract infections on in vitro Fertilization (IVF) outcome. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207684"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41385-019-0162-4","article-title":"Emerging roles of bile acids in mucosal immunity and inflammation","volume":"12","author":"Chen","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.bbrc.2021.09.061","article-title":"An elevated deoxycholic acid level induced by high-fat feeding damages intestinal stem cells by reducing the ileal IL-22","volume":"579","author":"Xu","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1007\/s10495-011-0633-x","article-title":"Deoxycholic and chenodeoxycholic bile acids induce apoptosis via oxidative stress in human colon adenocarcinoma cells","volume":"16","author":"Barrasa","year":"2011","journal-title":"Apoptosis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.freeradbiomed.2008.11.004","article-title":"Reactive oxygen-induced reactive oxygen formation during human sperm capacitation","volume":"46","author":"Lamothe","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_41","unstructured":"Biggers, J., Whitten, W., and Whittingham, D. (1971). The culture of mouse embryos in vitro. Methods in Mammalian Enbryology, W-H-Freeman-Co."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1530\/ror.0.0020048","article-title":"Reactive oxygen species and sperm physiology","volume":"2","author":"Jiang","year":"1997","journal-title":"Rev. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/hep.27204","article-title":"Bile acids alter male fertility through G-protein-coupled bile acid receptor 1 signaling pathways in mice","volume":"60","author":"Baptissart","year":"2014","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhao, S., Gong, Z., Zhou, J., Tian, C., Gao, Y., Xu, C., Chen, Y., Cai, W., and Wu, J. (2016). Deoxycholic Acid Triggers NLRP3 Inflammasome Activation and Aggravates DSS-Induced Colitis in Mice. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00536"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1095\/biolreprod55.3.684","article-title":"Cyclic adenosine 3\u2032, 5\u2032 monophosphate-dependent regulation of protein tyrosine phosphorylation in relation to human sperm capacitation and motility","volume":"55","author":"Leclerc","year":"1996","journal-title":"Biol. Reprod."},{"key":"ref_46","unstructured":"WHO (2021). WHO Laboratory Manual for the Examination and Processing of Human Semen, World Health Organization."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-1-62703-038-0_3","article-title":"The Hypo-Osmotic Swelling Test for Evaluation of Sperm Membrane Integrity","volume":"Volume 927","author":"Carrell","year":"2013","journal-title":"Spermatogenesis. Methods in Molecular Biology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/humrep\/deae268","article-title":"Sphingolipids modulate redox signalling during human sperm capacitation","volume":"40","author":"Serafini","year":"2025","journal-title":"Hum. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Serafini, S., and O\u2019Flaherty, C. (2025). Dysregulation of sphingolipid and cholesterol homeostasis imposes oxidative stress in human spermatozoa. Redox Biol., 84.","DOI":"10.1016\/j.redox.2025.103669"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/j.1939-4640.1990.tb03228.x","article-title":"Kinematics of human spermatozoa incubated under capacitating conditions","volume":"11","author":"Mortimer","year":"1990","journal-title":"J. Androl."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/j.1939-4640.1991.tb01610.x","article-title":"Intracellular calcium accumulation and responsiveness to progesterone in capacitating human spermatozoa","volume":"12","author":"Baldi","year":"1991","journal-title":"J. Androl."},{"key":"ref_52","first-page":"787","article-title":"Peroxiredoxin 6 regulates the phosphoinositide 3-kinase\/AKT pathway to maintain human sperm viability","volume":"25","author":"Fernandez","year":"2019","journal-title":"Mol. Hum. Reprod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.freeradbiomed.2003.08.010","article-title":"In situ detection and localization of lipid peroxidation in individual bovine sperm cells","volume":"35","author":"Brouwers","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1016\/j.freeradbiomed.2004.03.014","article-title":"Mass spectrometric characterization of the oxidation of the fluorescent lipid peroxidation reporter molecule C11-BODIPY(581\/591)","volume":"36","author":"Drummen","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_55","first-page":"106","article-title":"Peroxiredoxins prevent oxidative stress during human sperm capacitation","volume":"23","author":"Lee","year":"2017","journal-title":"Mol. Hum. Reprod."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Moawad, A.R., Fernandez, M.C., Scarlata, E., Dodia, C., Feinstein, S.I., Fisher, A.B., and O\u2019Flaherty, C. (2017). Deficiency of peroxiredoxin 6 or inhibition of its phospholipase A2 activity impair the in vitro sperm fertilizing competence in mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-13411-2"},{"key":"ref_57","unstructured":"Armstrong, D. (2010). Using Fluorescence-Activated Flow Cytometry to Determine Reactive Oxygen Species Formation and Membrane Lipid Peroxidation in Viable Boar Spermatozoa. Advanced Protocols in Oxidative Stress II, Humana Press."},{"key":"ref_58","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_59","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.freeradbiomed.2005.10.055","article-title":"Reactive oxygen species modulate independent protein phosphorylation pathways during human sperm capacitation","volume":"40","author":"Gagnon","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1600-0897.2007.00559.x","article-title":"Clinical Relevance of Oxidative Stress in Male Factor Infertility: An Update","volume":"59","author":"Agarwal","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1365-2605.2005.00630.x","article-title":"Sperm function tests and fertility","volume":"29","author":"Aitken","year":"2006","journal-title":"Int. J. Androl."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"14948","DOI":"10.1074\/jbc.M506710200","article-title":"Deoxycholic acid induces intracellular signaling through membrane perturbations","volume":"281","author":"Akare","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35660","DOI":"10.1074\/jbc.M113.519116","article-title":"Bile acids modulate signaling by functional perturbation of plasma membrane domains","volume":"288","author":"Zhou","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1194\/jlr.R900012-JLR200","article-title":"Bile acid transporters","volume":"50","author":"Dawson","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Klein, D.M., and Cherrington, N.J. (2014). Organic and inorganic transporters of the testis: A review. Spermatogenesis, 4.","DOI":"10.4161\/21565562.2014.979653"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1194\/jlr.M062653","article-title":"Deoxycholic acid modulates cell death signaling through changes in mitochondrial membrane properties","volume":"56","author":"Sousa","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1530\/REP-18-0203","article-title":"Activated-farnesoid X receptor (FXR) expressed in human sperm alters its fertilising ability","volume":"156","author":"Malivindi","year":"2018","journal-title":"Reproduction"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Abrigo, J., Olgu\u00edn, H., Tacchi, F., Orozco-Aguilar, J., Valero-Breton, M., Soto, J., Castro-Sep\u00falveda, M., Elorza, A.A., Simon, F., and Cabello-Verrugio, C. (2023). Cholic and deoxycholic acids induce mitochondrial dysfunction, impaired biogenesis and autophagic flux in skeletal muscle cells. Biol. Res., 56.","DOI":"10.1186\/s40659-023-00436-3"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1021\/cr200084z","article-title":"Free radical lipid peroxidation: Mechanisms and analysis","volume":"111","author":"Yin","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.3109\/10715762.2010.498477","article-title":"Chemistry and biochemistry of lipid peroxidation products","volume":"44","author":"Atalay","year":"2010","journal-title":"Free Radic. Res."},{"key":"ref_71","first-page":"1229","article-title":"Lipid peroxidation products and antioxidants in human disease","volume":"106","author":"Romero","year":"1998","journal-title":"Environ. Health Perspect."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/j.1365-2605.2010.01092.x","article-title":"The effect of paternal diet-induced obesity on sperm function and fertilization in a mouse model","volume":"34","author":"Bakos","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Baker, M.A., Weinberg, A., Hetherington, L., Villaverde, A.-I., Velkov, T., Baell, J., and Gordon, C.P. (2015). Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function. Biol. Reprod., 92.","DOI":"10.1095\/biolreprod.114.126680"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Alvarez, J.G., and Aitken, R.J. (2012). Lipid peroxidation in human spermatozoa. Studies on Men\u2019s Health and Fertility, Humana Press.","DOI":"10.1007\/978-1-61779-776-7_6"},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/nass\/44.1.139","article-title":"GC\u2192CG transversion mutation might be caused by 8-oxoguanine oxidation product","volume":"44","author":"Kino","year":"2000","journal-title":"Nucleic Acids Symp. Ser."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wyck, S., Herrera, C., Requena, C.E., Bittner, L., Hajkova, P., Bollwein, H., and Santoro, R. (2018). Oxidative stress in sperm affects the epigenetic reprogramming in early embryonic development. Epigenetics Chromatin, 11.","DOI":"10.1186\/s13072-018-0224-y"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Zikopoulos, A., Kojovic, V., Dimitriadis, F., Sofikitis, N., Chrisofos, M., and Zachariou, A. (2024). Paternal Contributions to Recurrent Pregnancy Loss: Mechanisms, Biomarkers, and Therapeutic Approaches. Medicina, 60.","DOI":"10.3390\/medicina60121920"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Moazamian, A., Saez, F., Drevet, J.R., Aitken, R.J., and Gharagozloo, P. (2025). Redox-Driven Epigenetic Modifications in Sperm: Unraveling Paternal Influences on Embryo Development and Transgenerational Health. Antioxidants, 14.","DOI":"10.3390\/antiox14050570"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/11\/1271\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:43:35Z","timestamp":1761183815000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/11\/1271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":79,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["antiox14111271"],"URL":"https:\/\/doi.org\/10.3390\/antiox14111271","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,22]]}}}