{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:38:22Z","timestamp":1791823102276,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,2]],"date-time":"2022-01-02T00:00:00Z","timestamp":1641081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Specialized pro-resolving lipid mediators regulate the resolution of acute inflammation. They are formed by enzymatic oxygenation of polyunsaturated fatty acids and are divided into families including lipoxins, resolvins, protectins, and maresins. Resolvin D1 (RvD1), produced by docosahexaenoic acid, exerts anti-inflammatory and pro-resolving activities. This research aimed to investigate the implication of seminal RvD1 in human infertility. Infertile patients (n\u00b0 67) were grouped based on pathological reproductive conditions as idiopathic infertility, varicocele, and leukocytospermia; the fourth group was composed of fertile men (n\u00b0 18). Sperm characteristics were evaluated by light microscopy (WHO guidelines) and by transmission electron microscopy (TEM). The seminal levels of RvD1 and F2-isoprostane (F2-IsoPs) were dosed. In twenty men (6 fertile men, 8 with varicocele, 6 with leukocytospermia) seminal phospholipase A2, iron, cholesterol, transferrin, estradiol, ferritin, testosterone, and sperm membrane fatty acids were detected. The results indicated that: (i) RvD1 amount was positively correlated with F2-IsoPs and reduced sperm quality; (ii) RvD1 levels were significantly higher in patients with leukocytospermia, varicocele, and idiopathic infertility compared to fertile men; (iii) RvD1 increased along with other markers of oxidative stress and inflammation as fatty acids content and clinical biomarkers. This study suggests a panel of inflammatory markers and lipid mediators for a diagnosis of inflammatory status and a subsequent appropriate therapeutic approach.<\/jats:p>","DOI":"10.3390\/antiox11010107","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T22:51:50Z","timestamp":1641250310000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Fatty Acid Oxidation and Pro-Resolving Lipid Mediators Are Related to Male Infertility"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0006-9414","authenticated-orcid":false,"given":"Cinzia","family":"Signorini","sequence":"first","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9467-0501","authenticated-orcid":false,"given":"Elena","family":"Moretti","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Noto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0306-9308","authenticated-orcid":false,"given":"Lucia","family":"Micheli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosetta","family":"Ponchia","sequence":"additional","affiliation":[{"name":"Unit of Medically Assisted Reproduction, Siena University Hospital, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1587-0159","authenticated-orcid":false,"given":"Giulia","family":"Collodel","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nri3859","article-title":"Eicosanoid storm in infection and inflammation","volume":"15","author":"Dennis","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106539","DOI":"10.1016\/j.prostaglandins.2021.106539","article-title":"Role of arachidonic cascade in COVID-19 infection: A review","volume":"154","author":"Ripon","year":"2021","journal-title":"Prostaglandins Other Lipid. Mediat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3892\/ijmm.2021.4947","article-title":"Role of 2-series prostaglandins in the pathogenesis of type 2 diabetes mellitus and non-alcoholic fatty liver disease","volume":"47","author":"Wang","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1042\/EBC20200018","article-title":"Specialized pro-resolving mediator network: An update on production and actions","volume":"64","author":"Chiang","year":"2020","journal-title":"Essays Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107879","DOI":"10.1016\/j.pharmthera.2021.107879","article-title":"Resolution of inflammation: An organizing principle in biology and medicine","volume":"227","author":"Panigrahy","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1084\/jem.20020760","article-title":"Resolvins: A family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals","volume":"196","author":"Serhan","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1172\/JCI97943","article-title":"Resolvins in inflammation: Emergence of the pro-resolving superfamily of mediators","volume":"128","author":"Serhan","year":"2018","journal-title":"J. Clin. Invest."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3267172","DOI":"10.1155\/2020\/3267172","article-title":"Resolution of Inflammation in Neurodegenerative Diseases: The Role of Resolvins","volume":"2020","author":"Chamani","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13479","article-title":"Pro-resolving lipid mediators are leads for resolution physiology","volume":"510","author":"Serhan","year":"2014","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.prostaglandins.2013.02.004","article-title":"Resolvin D1 and its GPCRs in resolution circuits of inflammation","volume":"107","author":"Recchiuti","year":"2013","journal-title":"Prostaglandins Other Lipid. Mediat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7038124","DOI":"10.1155\/2020\/7038124","article-title":"Relevance of Fatty Acids to Sperm Maturation and Quality","volume":"2020","author":"Collodel","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/andr.12024","article-title":"Dietary fatty acids affect semen quality: A review","volume":"3","author":"Esmaeili","year":"2015","journal-title":"Andrology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ferreira, G., Costa, C., Bassaizteguy, V., Santos, M., Cardozo, R., Montes, J., Settineri, R., and Nicolson, G.L. (2018). Incubation of human sperm with micelles made from glycerophospholipid mixtures increases sperm motility and resistance to oxidative stress. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197897"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e13126","DOI":"10.1111\/and.13126","article-title":"Role of oxidative stress, infection and inflammation in male infertility","volume":"50","author":"Agarwal","year":"2018","journal-title":"Andrologia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e13879","DOI":"10.1111\/and.13879","article-title":"Dietary supplements in the management of varicocele-induced infertility: A review of potential mechanisms","volume":"53","author":"Arab","year":"2021","journal-title":"Andrologia"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cannarella, R., Crafa, A., Barbagallo, F., Mongio\u00ec, L.M., Condorelli, R.A., Aversa, A., Calogero, A.E., and La Vignera, S. (2020). Seminal Plasma Proteomic Biomarkers of Oxidative Stress. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239113"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6612796","DOI":"10.1155\/2021\/6612796","article-title":"Research Progress on the Relationship between Obesity-Inflammation-Aromatase Axis and Male Infertility","volume":"2021","author":"Yuxin","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_18","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. Men\u2019s Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e12992","DOI":"10.1111\/aji.12992","article-title":"Identification of seminal markers of male accessory gland inflammation: From molecules to proteome","volume":"80","author":"Grande","year":"2018","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1684\/ecn.2018.0412","article-title":"Cytokines and male infertility","volume":"29","author":"Syriou","year":"2018","journal-title":"Eur. Cytokine Netw."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s12272-020-01299-y","article-title":"Role of specialized pro-resolving lipid mediators and their receptors in virus infection: A promising therapeutic strategy for SARS-CoV-2 cytokine storm","volume":"44","author":"Lee","year":"2021","journal-title":"Arch. Pharm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ejogrb.2020.08.015","article-title":"Emerging role of Novel Seminal Plasma Bio-markers in Male Infertility: A Review","volume":"253","author":"Kumar","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s43032-020-00260-0","article-title":"Semen Biochemical Components in Varicocele, Leukocytospermia, and Idiopathic Infertility","volume":"28","author":"Collodel","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_24","unstructured":"World Health Organization (2010). WHO Laboratory Manual for the Examination and Processing of Human Semen, WHO Press. [5th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/j.1939-4640.1995.tb00541.x","article-title":"Notulae seminologicae. 5. Mathematical evaluation of interdependent submicroscopic sperm alterations","volume":"16","author":"Baccetti","year":"1995","journal-title":"J. Androl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106","DOI":"10.2164\/jandrol.107.002998","article-title":"Morphology and meiotic segregation in spermatozoa from men of proven fertility","volume":"29","author":"Collodel","year":"2008","journal-title":"J. Androl."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1080\/13510002.2021.1884802","article-title":"Redox imbalance induced by docetaxel in the neuroblastoma SH-SY5Y cells: A study of docetaxel-induced neuronal damage","volume":"26","author":"Micheli","year":"2021","journal-title":"Redox Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.freeradbiomed.2019.05.014","article-title":"Increased isoprostanoid levels in brain from murine model of Krabbe disease\u2014Relevance of isoprostanes, dihomo-isoprostanes and neuroprostanes to disease severity","volume":"139","author":"Signorini","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.plefa.2014.08.002","article-title":"Altered erythrocyte membrane fatty acid profile in typical Rett syndrome: Effects of omega-3 polyunsaturated fatty acid supplementation. Prostaglandins Leukot","volume":"91","author":"Signorini","year":"2014","journal-title":"Essent. Fat. Acids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"805328","DOI":"10.1155\/2015\/805328","article-title":"A pilot comparative study of 26 biochemical markers in seminal plasma and serum in infertile men","volume":"2015","author":"Feng","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1074\/jbc.M507340200","article-title":"Release of free F2-iso-prostanes from esterified phospholipids is catalyzed by intracellular and plasma platelet activating factor acetylhydrolases","volume":"281","author":"Stafforini","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s12016-019-08754-9","article-title":"Resolvins: Emerging Players in Autoimmune and Inflammatory Diseases","volume":"58","author":"Abdolmaleki","year":"2020","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1093\/humupd\/dmy009","article-title":"Infectious, inflammatory and \u2018autoimmune\u2019 male factor infertility: How do rodent models inform clinical practice?","volume":"24","author":"Fijak","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1111\/andr.12236","article-title":"Fatty acids profiling reveals potential candidate markers of semen quality","volume":"4","author":"Zerbinati","year":"2016","journal-title":"Andrology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev.pathmechdis.3.121806.151409","article-title":"Anti-inflammatory and proresolving lipid mediators","volume":"3","author":"Serhan","year":"2008","journal-title":"Ann. Rev. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.1039\/C8AN01046C","article-title":"Lipid metabolism in inflammation-related diseases","volume":"143","author":"Zhang","year":"2018","journal-title":"Analyst"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.plipres.2017.09.004","article-title":"Isoprostanes, neuroprostanes and phytoprostanes: An overview of 25years of research in chemistry and biology","volume":"68","author":"Galano","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106448","DOI":"10.1016\/j.prostaglandins.2020.106448","article-title":"Relevance of seminal F2-dihomo-IsoPs, F2-IsoPs and F4-NeuroPs in idiopathic infertility and varicocele","volume":"149","author":"Longini","year":"2020","journal-title":"Prostaglandins Other Lipid. Mediat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1016\/j.ajpath.2015.08.008","article-title":"Resolvin D1 Reduces Emphysema and Chronic Inflammation","volume":"185","author":"Hsiao","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1096\/fj.06-7227rev","article-title":"Resolution of inflammation: State of the art, definitions and terms","volume":"21","author":"Serhan","year":"2007","journal-title":"FASEB J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3389\/fimmu.2016.00160","article-title":"Resolution of Inflammation: What Controls Its Onset?","volume":"7","author":"Sugimoto","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_42","first-page":"89","article-title":"Impact of inflammation on male fertility","volume":"3","author":"Sarkar","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00345-011-0726-8","article-title":"Influence of urogenital infections and inflammation on semen quality and male fertility","volume":"30","author":"Rusz","year":"2012","journal-title":"World J. Urol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jri.2013.05.001","article-title":"Markers of semen inflammation: Supplementary semen analysis?","volume":"100","author":"Condorelli","year":"2013","journal-title":"J. Reprod. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1111\/andr.12188","article-title":"Semen leukocytes and oxidative-dependent DNA damage of spermatozoa in male partners of subfertile couples with no symptoms of genital tract infection","volume":"4","author":"Micillo","year":"2016","journal-title":"Andrology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1111\/andr.12513","article-title":"Association between leukocytospermia and semen interleukin-6 and tumor necrosis factor-alpha in infertile men","volume":"6","author":"Eldamnhoury","year":"2018","journal-title":"Andrology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/andr.12511","article-title":"A global view of the pathophysiology of varicocele","volume":"6","author":"Hassanin","year":"2018","journal-title":"Andrology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2154548","DOI":"10.1155\/2019\/2154548","article-title":"The Impact of Food Service Attributes on Customer Satisfaction in a Rural University Campus Environment","volume":"2019","author":"Serhan","year":"2019","journal-title":"Int. J. Food Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1164\/rccm.200705-678OC","article-title":"Serum amyloid a is a biomarker of acute exacerbations of chronic obstructive pulmonary disease","volume":"177","author":"Bozinovski","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1073\/pnas.1109382109","article-title":"Serum amyloid A opposes lipoxin A4 to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease","volume":"109","author":"Bozinovski","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"390","DOI":"10.3389\/fimmu.2012.00390","article-title":"Resolvin D1 and Resolvin E1 Promote the Resolution of Allergic Airway Inflammation via Shared and Distinct Molecular Counter-Regulatory Pathways","volume":"3","author":"Levy","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/19396368.2018.1548668","article-title":"Associations between biochemical components of human semen with seminal conditions","volume":"65","author":"Collodel","year":"2019","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.plefa.2006.06.002","article-title":"Sperm fatty acid composition in subfertile men","volume":"75","author":"Aksoy","year":"2006","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1071\/RD14276","article-title":"Association of decreased spermatozoa omega-3 fatty acid levels and increased oxidative DNA damage with varicocele in infertile men: A case control study","volume":"28","author":"Tang","year":"2016","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5155","DOI":"10.1038\/s41598-018-23408-0","article-title":"Modeling the effects of lipid peroxidation during ferroptosis on membrane properties","volume":"8","author":"Agmon","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.theriogenology.2020.10.005","article-title":"Manipulation of fatty acid profiles in roosters\u2019 testes, alteration in sexual hormones, improvements in testicular histology characteristics and elevation sperm quality factor by L-carnitine","volume":"161","author":"Mohammadi","year":"2021","journal-title":"Theriogenology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3390\/nu2030355","article-title":"Omega-3 fatty acids and inflammatory processes","volume":"2","author":"Calder","year":"2010","journal-title":"Nutrients"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/1\/107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:59:55Z","timestamp":1760363995000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/1\/107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,2]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["antiox11010107"],"URL":"https:\/\/doi.org\/10.3390\/antiox11010107","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,2]]}}}