{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:45:22Z","timestamp":1784951122743,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Peroxisome Proliferator-Activated Receptor Gamma (PPAR\u03b3) is a regulating agent in antioxidant response also involved in controlling inflammation. The impact of varicocele and urogenital infections on sperm PPAR\u03b3 expression was studied. The PPAR\u03b3 gene expression was investigated in spermatozoa of 26 normozoospermic men grouped according to their clinical conditions: normal semen parameters (N), normal semen parameters and varicocele (N + V), and normal semen parameters and urogenital infections (N + UI). Sperm PPAR\u03b3 expression was correlated with F2-isoprostanes (F2-IsoPs), as markers of lipid peroxidation, and Resolvin D1 (RvD1), a pro-resolving mediator in inflammation. Sperm PPAR\u03b3 expression was evaluated through comparative real-time PCR, and F2-IsoPs and RvD1 were quantified in the seminal plasma via GC\/NCI-MS\/MS and immunoassay, respectively. PPAR\u03b3 expression correlates positively with sperm morphology and vitality and negatively with F2-IsoPs and RvD1. Sperm morphology positively correlates with vitality and negatively with F2-IsoP and RvD1 levels. Despite the normozoospermia in the three examined groups, sperm morphology and PPAR\u03b3 expression were significantly reduced in N + V and N + UI groups compared to the N group. Additionally, F2-IsoP and RvD1 levels were elevated in N + V and N + UI patients. These data suggest that PPAR\u03b3 expression is compromised by inflammation and lipoperoxidation, providing new insights to further explore new possibilities of targeted treatment of male infertility.<\/jats:p>","DOI":"10.3390\/biology14020137","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T03:26:10Z","timestamp":1738121170000},"page":"137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PPAR\u03b3 Expression in Human Spermatozoa and Its Relationship with Seminal F2-Isoprostanes and Resolvin D1 in the Presence of Varicocele and Urogenital Infections"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1587-0159","authenticated-orcid":false,"given":"Giulia","family":"Collodel","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"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5682-4148","authenticated-orcid":false,"given":"Caterina","family":"Marcucci","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\/0009-0008-5563-236X","authenticated-orcid":false,"given":"Laura","family":"Liguori","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\/0000-0002-8380-7453","authenticated-orcid":false,"given":"Daniela","family":"Marchini","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9091-8952","authenticated-orcid":false,"given":"Roberta","family":"Corsaro","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\/0000-0002-6113-7401","authenticated-orcid":false,"given":"Gabriele","family":"Centini","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\/0000-0003-0006-9414","authenticated-orcid":false,"given":"Cinzia","family":"Signorini","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":[[2025,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/molehr\/6.3.226","article-title":"Fatty acid composition of spermatozoa and immature germ cells","volume":"6","author":"Lenzi","year":"2000","journal-title":"Mol. Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vall\u00e9s, A.S., Avelda\u00f1o, M.I., and Furland, N.E. (2014). Altered lipid homeostasis in Sertoli cells stressed by mild hyperthermia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091127"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/19396368.2019.1677801","article-title":"Peroxisome Proliferator-Activated Receptors (PPARs) levels in spermatozoa of normozoospermic and asthenozoospermic men","volume":"65","author":"Mousavi","year":"2019","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.theriogenology.2020.11.022","article-title":"Effect of rosiglitazone on developmental competence of mouse embryos treated with lipopolysaccharide","volume":"161","author":"Moghadam","year":"2021","journal-title":"Theriogenology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ejphar.2015.11.004","article-title":"Fatty acids, eicosanoids and PPAR gamma","volume":"785","author":"Savoye","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1080\/19396368.2019.1626934","article-title":"New insights into sperm with total globozoospermia: Increased fatty acid oxidation and centrin1 alteration","volume":"65","author":"Moretti","year":"2019","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/jcp.20807","article-title":"Peroxisome proliferator-activated receptor (PPAR)\u03b3 is expressed by human spermatozoa: Its potential role on the sperm physiology","volume":"209","author":"Aquila","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"942","DOI":"10.4103\/1008-682X.150253","article-title":"Peroxisome proliferator-activated receptor gamma signaling in human sperm physiology","volume":"17","author":"Liu","year":"2015","journal-title":"Asian J. Androl."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shibata, T., Bhat, S.A., Cao, D., Saito, S., Bernstein, E.A., Nishi, E., Medenilla, J.D., Wang, E.T., Chan, J.L., and Pisarska, M.D. (2024). Testicular ACE regulates sperm metabolism and fertilization through the transcription factor PPAR\u03b3. J. Biol. Chem., 300.","DOI":"10.1016\/j.jbc.2023.105486"},{"key":"ref_10","unstructured":"WHO (2021). WHO Laboratory Manual for the Examination and Processing of Human Semen, WHO. [6th ed.]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e13614","DOI":"10.1111\/and.13614","article-title":"Diagnostic value of routine semen analysis in clinical andrology","volume":"53","author":"Baskaran","year":"2021","journal-title":"Andrologia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e13861","DOI":"10.1111\/and.13861","article-title":"Normal sperm parameters per se do not reliably account for fertility: A case-control study in the real-life setting","volume":"53","author":"Boeri","year":"2021","journal-title":"Andrologia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrurol.2017.98","article-title":"Varicocele and male infertility","volume":"14","author":"Jensen","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/19396368.2020.1793032","article-title":"Role of isoprostanes in human male infertility","volume":"66","author":"Signorini","year":"2020","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_15","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_16","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_17","doi-asserted-by":"crossref","unstructured":"Aitken, R.J., and Drevet, J.R. (2020). The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword. Antioxidants, 9.","DOI":"10.3390\/antiox9020111"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e34799","DOI":"10.1016\/j.heliyon.2024.e34799","article-title":"Role of pyridoxine and oxidative stress in asthenozoospermia","volume":"10","author":"Bdeir","year":"2024","journal-title":"Heliyon"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"O\u2019flaherty, C. (2018). Peroxiredoxin 6: The Protector of Male Fertility. Antioxidants, 7.","DOI":"10.3390\/antiox7120173"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.bbalip.2014.10.007","article-title":"The isoprostanes\u201425 years later","volume":"1851","author":"Milne","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Collodel, G., Moretti, E., Noto, D., Corsaro, R., and Signorini, C. (2022). Oxidation of Polyunsaturated Fatty Acids as a Promising Area of Research in Infertility. Antioxidants, 11.","DOI":"10.3390\/antiox11051002"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","unstructured":"Signorini, C., Moretti, E., Noto, D., Micheli, L., Ponchia, R., and Collodel, G. (2022). Fatty Acid Oxidation and Pro-Resolving Lipid Mediators Are Related to Male Infertility. Antioxidants, 11.","DOI":"10.3390\/antiox11010107"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","unstructured":"Moretti, E., Signorini, C., Ferretti, F., Noto, D., and Collodel, G. (2022). A Study to Validate the Relevance of Semen F2-Isoprostanes on Human Male Infertility. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19031642"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"641087","DOI":"10.1155\/2012\/641087","article-title":"PPAR\u03b3 and Oxidative Stress: Con(\u03b2) Catenating NRF2 and FOXO","volume":"2012","author":"Polvani","year":"2012","journal-title":"PPAR Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Xia, H., Wang, J., Sun, S., Wang, F., Yang, Y., Chen, L., Sun, Z., and Yao, S. (2019). Resolvin D1 Alleviates Ventilator-Induced Lung Injury in Mice by Activating PPAR\u03b3\/NF-\u03baB Signaling Pathway. BioMed Res. Int., 2019.","DOI":"10.1155\/2019\/6254587"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.bbadis.2011.02.014","article-title":"PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation","volume":"1812","author":"Varga","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Muzio, G., Barrera, G., and Pizzimenti, S. (2021). Peroxisome Proliferator-Activated Receptors (PPARs) and Oxidative Stress in Physiological Conditions and in Cancer. Antioxidants, 10.","DOI":"10.3390\/antiox10111734"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1378175","DOI":"10.1155\/2017\/1378175","article-title":"Collaborative Power of Nrf2 and PPAR\u03b3 Activators against Metabolic and Drug-Induced Oxidative Injury","volume":"2017","author":"Lee","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10571-017-0554-5","article-title":"Roles of Peroxisome Prolif-erator-Activated Receptor Gamma on Brain and Peripheral Inflammation","volume":"38","author":"Villapol","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_33","first-page":"1085","article-title":"Sperm metabolism in pigs: A role for peroxisome proliferator-activated receptor gamma (PPAR\u03b3)","volume":"216","author":"Santoro","year":"2013","journal-title":"J. Exp. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Antonuccio, P., Marini, H.R., Micali, A., Romeo, C., Granese, R., Retto, A., Martino, A., Benvenga, S., Cuzzocrea, S., and Impellizzeri, D. (2021). The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele. Nutrients, 13.","DOI":"10.3390\/nu13030734"},{"key":"ref_35","first-page":"819","article-title":"Steroid receptors in human ejaculated sperm as molecular markers of the detrimental effects related to the pathophysiology of testicular varicocele","volume":"31","author":"Perrotta","year":"2016","journal-title":"Histol. Histopathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.fertnstert.2004.02.112","article-title":"Novel associations between specific sperm morphological defects and leukocytospermia","volume":"82","author":"Aziz","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/and.12324","article-title":"How accurate is sperm morphology as an indicator of sperm function?","volume":"47","author":"Franken","year":"2015","journal-title":"Andrologia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.fertnstert.2021.12.012","article-title":"The sixth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen: Ensuring quality and standardization in basic examination of human ejaculates","volume":"117","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s42826-024-00204-8","article-title":"Eltroxin and Hesperidin mitigate testicular and renal damage in hypothyroid rats: Amelioration of oxidative stress through PPAR\u03b3 and Nrf2\/HO-1 signaling pathway","volume":"40","author":"Osama","year":"2024","journal-title":"Lab. Anim. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.amjhyper.2005.11.006","article-title":"Modulation of cardiac and aortic peroxisome proliferator-activated receptor-\u03b3 expression by oxidative stress in chronically glucose-fed rats","volume":"19","author":"Wu","year":"2006","journal-title":"Am. J. Hypertens."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/j.freeradbiomed.2010.03.007","article-title":"Oxidative stress modulates PPAR \u03b3 in vascular endothelial cells","volume":"48","author":"Blanquicett","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44464","DOI":"10.1074\/jbc.M112.422626","article-title":"SUMO-specific protease 1 regulates mitochondrial biogenesis through PGC-1\u03b1","volume":"287","author":"Cai","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S1388-1981(02)00126-9","article-title":"Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: Evidence for a PPAR \u03b3-dependent mechanism","volume":"1581","author":"Yu","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1530\/REP-18-0009","article-title":"Epigenetic reprogramming during spermatogenesis and male factor infertility","volume":"156","author":"McSwiggin","year":"2018","journal-title":"Reproduction"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1262\/jrd.2016-093","article-title":"Is transcription in sperm stationary or dynamic?","volume":"63","author":"Ren","year":"2017","journal-title":"J. Reprod. Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/humupd\/dmab034","article-title":"All you need to know about sperm RNAs","volume":"28","author":"Santiago","year":"2021","journal-title":"Hum. Reprod. Update"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.freeradbiomed.2017.10.342","article-title":"Melatonin reduces oxidative damage and upregulates heat shock protein 90 expression in cryopreserved human semen","volume":"113","author":"Deng","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1007\/s43032-021-00572-9","article-title":"Protective Effects of Curcumin on the Outcome of Cryopreservation in Human Sperm","volume":"28","author":"Santonastaso","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_49","first-page":"72","article-title":"Expression and immunolocalisation of PPAR\u03b3 in reproductive tissues of rabbits fed n-3 PUFA-enriched diets","volume":"18","author":"Passaponti","year":"2022","journal-title":"J. Men\u2019s Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/1465-9921-13-110","article-title":"Resolvin D1 attenuates inflammation in lipopolysaccharide-induced acute lung injury through a process involving the PPAR\u03b3\/NF-\u03baB pathway","volume":"13","author":"Liao","year":"2012","journal-title":"Respir. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13397","DOI":"10.1111\/jcmm.15963","article-title":"Effect of RvD1\/FPR2 on inflammatory response in chorioamnionitis","volume":"24","author":"Li","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mattioli, S., Moretti, E., Castellini, C., Signorini, C., Corsaro, R., Angelucci, E., and Collodel, G. (2023). Can Dietary n-3 Polyunsaturated Fatty Acids Affect Apelin and Resolvin in Testis and Sperm of Male Rabbits?. Molecules, 28.","DOI":"10.3390\/molecules28176188"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1093\/humrep\/deaa153","article-title":"Peroxisome proliferator-activated receptor gamma expression along the male genital system and its role in male fertility","volume":"35","author":"Santoro","year":"2020","journal-title":"Hum. 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