{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T03:15:04Z","timestamp":1767842104798,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["SFRH\/BD\/136779\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136779\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["COVID\/BD\/153209\/2023"],"award-info":[{"award-number":["COVID\/BD\/153209\/2023"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UI\/BD\/150749\/2020"],"award-info":[{"award-number":["UI\/BD\/150749\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["2021.03439.CEECIND"],"award-info":[{"award-number":["2021.03439.CEECIND"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["2022.10533.BD"],"award-info":[{"award-number":["2022.10533.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007491"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007491"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Mitochondrial uncoupling proteins (UCPs) are central in the regulation of mitochondrial activity and reactive oxygen species (ROS) production. High oxidative stress is a major cause of male infertility; however, UCPs expression and function in human spermatozoa are still unknown. Herein, we aimed to assess the expression and function of the different homologs (UCP1-6) in human spermatozoa. For this purpose, we screened for the mRNA expression of all UCP homologs. Protein expression and immunolocalization of UCP1, UCP2, and UCP3 were also assessed. Highly motile spermatozoa were isolated from human normozoospermic seminal samples (n = 16) and incubated with genipin, an inhibitor of UCPs (0, 0.5, 5, and 50 \u00b5M) for 3 h at 37 \u00b0C. Viability and total motility were assessed. Mitochondrial membrane potential and ROS production were evaluated. Media were collected and the metabolic profile and antioxidant potential were analyzed by 1H-NMR and FRAP, respectively. The expression of all UCP homologs (UCP1-6) mRNA by human spermatozoa is herein reported for the first time. UCP1-3 are predominant at the head equatorial segment, whereas UCP1 and UCP2 are also expressed at the spermatozoa midpiece, where mitochondria are located. The inhibition of UCPs by 50 \u00b5M genipin, resulting in the UCP3 inhibition, did not compromise sperm cell viability but resulted in irreversible total motility loss that persisted despite washing or incubation with theophylline, a cAMP activator. These effects were associated with decreased mitochondrial membrane potential and lactate production. No differences concerning UCP3 expression, however, were observed in spermatozoa from normozoospermic versus asthenozoospermic men (n = 6). The inhibition of UCPs did not increase ROS production, possibly due to the decreased mitochondrial activity and genipin antioxidant properties. In sum, UCPs are major regulators of human spermatozoa motility and metabolism. The discovery and characterization of UCPs\u2019 role in human spermatozoa can shed new light on spermatozoa ROS-related pathways and bioenergetics physiology.<\/jats:p>","DOI":"10.3390\/antiox12020409","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T03:57:16Z","timestamp":1675828636000},"page":"409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of Mitochondrial Uncoupling Proteins Arrests Human Spermatozoa Motility without Compromising Viability"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0546-3480","authenticated-orcid":false,"given":"David F.","family":"Carrageta","sequence":"first","affiliation":[{"name":"Endocrine and Metabolic Research, UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Physiology, Department of Immuno-Physiology and Pharmacology, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1423-5869","authenticated-orcid":false,"given":"La\u00eds","family":"Freire-Brito","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Research, UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Physiology, Department of Immuno-Physiology and Pharmacology, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3276-5094","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Guerra-Carvalho","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Research, UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Physiology, Department of Immuno-Physiology and Pharmacology, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4200-465 Porto, Portugal"},{"name":"Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-8875","authenticated-orcid":false,"given":"Jo\u00e3o C.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Research, UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Physiology, Department of Immuno-Physiology and Pharmacology, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4200-465 Porto, Portugal"},{"name":"Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Bruno S.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Research, UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Physiology, Department of Immuno-Physiology and Pharmacology, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Alberto","family":"Barros","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Centre for Reproductive Genetics Prof. Alberto Barros, 4100-012 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-5699","authenticated-orcid":false,"given":"Pedro F.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-1831","authenticated-orcid":false,"given":"Mariana P.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Research, UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-783X","authenticated-orcid":false,"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Research, UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Physiology, Department of Immuno-Physiology and Pharmacology, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Monteiro, B.S., Freire-Brito, L., Carrageta, D.F., Oliveira, P.F., and Alves, M.G. 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