{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:32:42Z","timestamp":1776353562494,"version":"3.51.2"},"reference-count":52,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Catania","award":["PIACERI 2020 funds"],"award-info":[{"award-number":["PIACERI 2020 funds"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In a previous study, we showed that various low-molecular-weight compounds in follicular fluid (FF) samples of control fertile females (CFF) have different concentrations compared to those found in FF of infertile females (IF), before and after their categorization into different subgroups, according to their clinical diagnosis of infertility. Using the same FF samples of this previous study, we here analyzed the FF concentrations of free and bound bilirubin and compared the results obtained in CFF, IF and the different subgroups of IF (endometriosis, EM, polycystic ovary syndrome, PCOS, age-related reduced ovarian reserve, AR-ROR, reduced ovarian reserve, ROR, genetic infertility, GI and unexplained infertility, UI). The results clearly indicated that CFF had lower values of free, bound and total bilirubin compared to the respective values measured in pooled IF. These differences were observed even when IF were categorized into EM, PCOS, AR-ROR, ROR, GI and UI, with EM and PCOS showing the highest values of free, bound and total bilirubin among the six subgroups. Using previous results of ascorbic acid, GSH and nitrite + nitrate measured in the same FF samples of the same FF donors, we found that total bilirubin in FF increased as a function of decreased values of ascorbic acid and GSH, and increased concentrations of nitrite + nitrate. The values of total bilirubin negatively correlated with the clinical parameters of fertilization procedures (number of retrieved oocytes, mature oocytes, fertilized oocytes, blastocysts, high-quality blastocysts) and with clinical pregnancies and birth rates. Bilirubin concentrations in FF were not linked to those found in serum samples of FF donors, thereby strongly suggesting that its over production was due to higher activity of heme oxygenase-1 (HO-1), the key enzyme responsible for bilirubin formation, in granulosa cells, or cumulus cells or oocytes of IF and ultimately leading to bilirubin accumulation in FF. Since increased activity of HO-1 is one of the main enzymatic intracellular mechanisms of defense towards external insults (oxidative\/nitrosative stress, inflammation), and since we found correlations among bilirubin and oxidative\/nitrosative stress in these FF samples, it may reasonably be supposed that bilirubin increase in FF of IF is the result of protracted exposures to the aforementioned insults evidently playing relevant roles in female infertility.<\/jats:p>","DOI":"10.3390\/ijms241310707","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"10707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Bilirubin Concentration in Follicular Fluid Is Increased in Infertile Females, Correlates with Decreased Antioxidant Levels and Increased Nitric Oxide Metabolites, and Negatively Affects Outcome Measures of In Vitro Fertilization"],"prefix":"10.3390","volume":"24","author":[{"given":"Renata","family":"Mangione","sequence":"first","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of Rome, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Pallisco","sequence":"additional","affiliation":[{"name":"Laboratory of Andrology and Embriology, Alma Res Fertility Center, Via Parenzo 12, 00198 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Bilotta","sequence":"additional","affiliation":[{"name":"Laboratory of Andrology and Embriology, Alma Res Fertility Center, Via Parenzo 12, 00198 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Marroni","sequence":"additional","affiliation":[{"name":"Laboratory of Andrology and Embriology, Alma Res Fertility Center, Via Parenzo 12, 00198 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9430-4723","authenticated-orcid":false,"given":"Valentina","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Aging, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Capoccia","sequence":"additional","affiliation":[{"name":"Laboratory of Andrology and Embriology, Alma Res Fertility Center, Via Parenzo 12, 00198 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-7279","authenticated-orcid":false,"given":"Giuseppe","family":"Lazzarino","sequence":"additional","affiliation":[{"name":"Division of Medical Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"},{"name":"LTA\u2014Biotech srl, Viale Don Orione 3D, 95047 Patern\u00f2, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-0895","authenticated-orcid":false,"given":"Barbara","family":"Tavazzi","sequence":"additional","affiliation":[{"name":"Departmental Faculty of Medicine and Surgery, UniCamillus\u2014Saint Camillus International University of Health and Medical Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-0966","authenticated-orcid":false,"given":"Giacomo","family":"Lazzarino","sequence":"additional","affiliation":[{"name":"Departmental Faculty of Medicine and Surgery, UniCamillus\u2014Saint Camillus International University of Health and Medical Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Bilotta","sequence":"additional","affiliation":[{"name":"Service of Obstetrics and Gynecology, Alma Res Fertility Center, Via Parenzo 12, 00198 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-9955","authenticated-orcid":false,"given":"Angela Maria","family":"Amorini","sequence":"additional","affiliation":[{"name":"Division of Medical Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brinca, A.T., Ramalhinho, A.C., Sousa, \u00c2., Oliani, A.H., Breitenfeld, L., Passarinha, L.A., and Gallardo, E. (2022). Follicular Fluid: A Powerful Tool for the Understanding and Diagnosis of Polycystic Ovary Syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061254"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"118174","DOI":"10.1016\/j.lfs.2020.118174","article-title":"miRNAs as a novel clinical biomarker and therapeutic targets in polycystic ovary syndrome (PCOS): A review","volume":"259","author":"Abdalla","year":"2020","journal-title":"Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20531","DOI":"10.1038\/s41598-022-24775-5","article-title":"Comparative metabolomic profiling of women undergoing in vitro fertilization procedures reveals potential infertility-related biomarkers in follicular fluid","volume":"12","author":"Dabaja","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1132621","DOI":"10.3389\/fendo.2023.1132621","article-title":"Metabonomic analysis of follicular fluid in patients with diminished ovarian reserve","volume":"14","author":"Li","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/mrd.23415","article-title":"Relationship between the metabolic and lipid profile in follicular fluid of women undergoing in vitro fertilization","volume":"87","author":"Luti","year":"2020","journal-title":"Mol. Reprod. Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.freeradbiomed.2015.05.013","article-title":"Metabolism alteration in follicular niche: The nexus among intermediary metabolism, mitochondrial function, and classic polycystic ovary syndrome","volume":"86","author":"Zhao","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.fertnstert.2014.11.002","article-title":"Endometriosis may be associated with mitochondrial dysfunction in cumulus cells from subjects undergoing in vitro fertilization-intracytoplasmic sperm injection, as reflected by decreased adenosine triphosphate production","volume":"103","author":"Hsu","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.fertnstert.2012.03.052","article-title":"Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis","volume":"98","author":"Prieto","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7265238","DOI":"10.1155\/2017\/7265238","article-title":"Oxidative Stress and Endometriosis: A Systematic Review of the Literature","volume":"2017","author":"Scutiero","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1073\/pnas.61.2.748","article-title":"The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase","volume":"61","author":"Tenhunen","year":"1968","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1089\/15230860260220094","article-title":"Heme degradation and human disease: Diversity is the soul of life","volume":"4","author":"Shibahara","year":"2002","journal-title":"Antioxid. Redox Signal."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sferrazzo, G., Di Rosa, M., Barone, E., Li Volti, G., Musso, N., Tibullo, D., and Barbagallo, I. (2020). Heme Oxygenase-1 in Central Nervous System Malignancies. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051562"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bianco, A., Tiribelli, C., and Bellarosa, C. (2022). Translational Approach to the Protective Effect of Bilirubin in Diabetic Kidney Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030696"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1007\/s11064-022-03810-x","article-title":"Bilirubin Induces A1-Like Reactivity of Astrocyte","volume":"48","author":"Li","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s00204-020-02659-9","article-title":"Bilirubin disrupts calcium homeostasis in neonatal hippocampal neurons: A new pathway of neurotoxicity","volume":"94","author":"Rauti","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12013-021-01047-z","article-title":"Heme Oxygenase 1 in Vertebrates: Friend and Foe","volume":"80","author":"Correa","year":"2022","journal-title":"Cell Biochem. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1089\/ars.2016.6735","article-title":"The Heme Oxygenase System in Hematological Malignancies","volume":"27","author":"Tibullo","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5695723","DOI":"10.1155\/2020\/5695723","article-title":"The Nrf-2\/HO-1 Signaling Axis: A Ray of Hope in Cardiovascular Diseases","volume":"2020","author":"Zhang","year":"2020","journal-title":"Cardiol. Res. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Menon, R., and Peltier, M.R. (2020). Novel Insights into the Regulatory Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 in Oxidative Stress and Inflammation of Human Fetal Membranes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176139"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Park, C., Cha, H.J., Hwangbo, H., Ji, S.Y., Kim, D.H., Kim, M.Y., Bang, E., Hong, S.H., Kim, S.O., and Jeong, S.J. (2023). Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054637"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ryter, S.W. (2022). Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders. Antioxidants, 11.","DOI":"10.3390\/antiox11030555"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Haines, D.D., and Tosaki, A. (2020). Heme Degradation in Pathophysiology of and Countermeasures to Inflammation-Associated Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249698"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1144323","DOI":"10.3389\/fendo.2023.1144323","article-title":"Astaxanthin ameliorates inflammation, oxidative stress, and reproductive outcomes in endometriosis patients undergoing assisted reproduction: A randomized, triple-blind placebo-controlled clinical trial","volume":"14","author":"Rostami","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Che\u0142chowska, M., Jurczewska, J., Gajewska, J., Mazur, J., Szostak-W\u0119gierek, D., Rudnicka, E., and Ambroszkiewicz, J. (2023). Antioxidant Defense Expressed as Glutathione Status and Keap1-Nrf2 System Action in Relation to Anthropometric Parameters and Body Composition in Young Women with Polycystic Ovary Syndrome. Antioxidants, 12.","DOI":"10.3390\/antiox12030730"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12958-018-0343-0","article-title":"Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: A randomized controlled trial","volume":"16","author":"Xu","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eabq5858","DOI":"10.1126\/scitranslmed.abq5858","article-title":"A long-acting anti-IL-8 antibody improves inflammation and fibrosis in endometriosis","volume":"15","author":"Sato","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1086232","DOI":"10.3389\/fimmu.2023.1086232","article-title":"Chitosan oligosaccharide improves ovarian granulosa cells inflammation and oxidative stress in patients with polycystic ovary syndrome","volume":"14","author":"Xie","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Collodel, G., Gambera, L., Stendardi, A., Nerucci, F., Signorini, C., Pisani, C., Marcheselli, M., Vellucci, F.L., Pizzasegale, S.E., and Micheli, L. (2023). Follicular Fluid Components in Reduced Ovarian Reserve, Endometriosis, and Idiopathic Infertility. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032589"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lazzarino, G., Pallisco, R., Bilotta, G., Listorti, I., Mangione, R., Saab, M.W., Caruso, G., Amorini, A.M., Brundo, M.V., and Lazzarino, G. (2021). Altered Follicular Fluid Metabolic Pattern Correlates with Female Infertility and Outcome Measures of In Vitro Fertilization. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168735"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/S0015-0282(16)59770-2","article-title":"Spectrophotometric absorbance of follicular fluid: A predictor of oocyte fertilizing capability","volume":"49","author":"Bayer","year":"1988","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/S0015-0282(16)55443-0","article-title":"Further study and characterization of the yellow pigments in follicular fluid that are related to oocyte quality","volume":"58","author":"Bayer","year":"1992","journal-title":"Fertil. Steril."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.fertnstert.2022.07.023","article-title":"Characterizing the follicular fluid metabolome: Quantifying the correlation across follicles and differences with the serum metabolome","volume":"118","author":"Hood","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_33","first-page":"1","article-title":"Heme oxygenase\/carbon monoxide in the female reproductive system: An overlooked signalling pathway","volume":"8","year":"2017","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"ref_34","unstructured":"(2023, June 03). National Center for Biotechnology Information, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/3163."},{"key":"ref_35","unstructured":"(2023, June 03). National Center for Biotechnology Information, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/3162."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fcell.2016.00080","article-title":"Therapeutic Efficacy of Stem Cells Transplantation in Diabetes: Role of Heme Oxygenase","volume":"4","author":"Raffaele","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Camiolo, G., Tibullo, D., Giallongo, C., Romano, A., Parrinello, N.L., Musumeci, G., Di Rosa, M., Vicario, N., Brundo, M.V., and Amenta, F. (2019). \u03b1-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030609"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1177\/1933719114525268","article-title":"Inducible nitric oxide synthase and heme oxygenase 1 are expressed in human cumulus cells and may be used as biomarkers of oocyte competence","volume":"21","author":"Bergandi","year":"2014","journal-title":"Reprod. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1007\/s10815-020-01806-6","article-title":"Morphokinetic analysis of cleavage stage embryos and assessment of specific gene expression in cumulus cells independently predict human embryo development to expanded blastocyst: A preliminary study","volume":"37","author":"Canosa","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"114606","DOI":"10.1016\/j.biopha.2023.114606","article-title":"Cellular Red-Ox system in health and disease: The latest update","volume":"162","author":"Jena","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Maldonado, E., Morales-Pison, S., Urbina, F., and Solari, A. (2023). Aging Hallmarks and the Role of Oxidative Stress. Antioxidants, 12.","DOI":"10.3390\/antiox12030651"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109601","DOI":"10.1016\/j.abb.2023.109601","article-title":"Activation of Nrf2 pathway as a protective mechanism against oxidative stress-induced diseases: Potential of astaxanthin","volume":"741","author":"Kanwugu","year":"2023","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e13918","DOI":"10.1111\/apha.13918","article-title":"Heme oxygenase-1 prevents non-alcoholic steatohepatitis through modulating mitochondrial quality control","volume":"237","author":"Li","year":"2023","journal-title":"Acta Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104024","DOI":"10.1016\/j.etap.2022.104024","article-title":"Heme oxygenase-1 protects against PM2.5 induced endothelial dysfunction through inhibition of HIF1\u03b1","volume":"97","author":"Xu","year":"2023","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/pr.2015.22","article-title":"Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation","volume":"77","author":"Schulz","year":"2015","journal-title":"Pediatr. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Castilho, \u00c1., Aveleira, C.A., Leal, E.C., Sim\u00f5es, N.F., Fernandes, C.R., Meirinhos, R.I., Baptista, F.I., and Ambr\u00f3sio, A.F. (2012). Heme oxygenase-1 protects retinal endothelial cells against high glucose- and oxidative\/nitrosative stress-induced toxicity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042428"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1056\/NEJMoa025039","article-title":"Adherence to a Mediterranean diet and survival in a Greek population","volume":"348","author":"Trichopoulou","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/clc.4960130809","article-title":"Metabolic equivalents (METS) in exercise testing, exercise prescription, and evaluation of functional capacity","volume":"13","author":"Sidney","year":"1990","journal-title":"Clin. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.chroma.2017.10.053","article-title":"Single-step preparation of selected biological fluids for the high performance liquid chromatographic analysis of fat-soluble vitamins and antioxidants","volume":"1527","author":"Lazzarino","year":"2017","journal-title":"J. Chromatogr. A"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lazzarino, G., Listorti, I., Bilotta, G., Capozzolo, T., Amorini, A.M., Longo, S., Caruso, G., Lazzarino, G., Tavazzi, B., and Bilotta, P. (2019). Water- and Fat-Soluble Antioxidants in Human Seminal Plasma and Serum of Fertile Males. Antioxidants, 8.","DOI":"10.3390\/antiox8040096"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1093\/humrep\/dey279","article-title":"Low-molecular weight compounds in human seminal plasma as potential biomarkers of male infertility","volume":"33","author":"Lazzarino","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lazzarino, G., Mangione, R., Saab, M.W., Tavazzi, B., Pittal\u00e0, A., Signoretti, S., Di Pietro, V., Lazzarino, G., and Amorini, A.M. (2023). Traumatic Brain Injury Alters Cerebral Concentrations and Redox States of Coenzymes Q9 and Q10 in the Rat. Antioxidants, 12.","DOI":"10.3390\/antiox12050985"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10707\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:01:45Z","timestamp":1760126505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,27]]},"references-count":52,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310707"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310707","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,27]]}}}