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Aquaglyceroporins, a subclass of aquaporins (AQPs), facilitate the transport of water and glycerol across the sperm membrane, with glycerol serving as an important substrate for sperm bioenergetics. This study aimed to elucidate the significance of AQP-mediated glycerol permeability in sperm motility. The presence and localization of AQP3 and AQP7 in human sperm were assessed using immunofluorescence. Subsequently, the glycerol permeability of spermatozoa obtained from normozoospermic individuals (n = 30) was measured, using stopped-flow light scattering, after incubation with specific aquaporin inhibitors targeting AQP3 (DFP00173), AQP7 (Z433927330), or general aquaglyceroporin (phloretin). Sperm from asthenozoospermic men (n = 30) were utilized to evaluate the AQP7-mediated glycerol permeability, and to compare it with that of normozoospermic men. Furthermore, hypermotile capacitated sperm cells were examined, to determine the AQP7 expression and membrane glycerol permeability. AQP3 was predominantly observed in the tail region, while AQP7 was present in the head, midpiece, and tail of human sperm. Our findings indicate that AQP7 plays a key role in glycerol permeability, as the inhibition of AQP7 resulted in a 55% decrease in glycerol diffusion across the sperm membrane. Importantly, this glycerol permeability impairment was evident in spermatozoa from asthenozoospermic individuals, suggesting the dysregulation of AQP7-mediated glycerol transport, despite similar AQP7 levels. Conversely, the AQP7 expression increased in capacitated sperm, compared to non-capacitated sperm. Hence, AQP7-mediated permeability may serve as a valuable indicator of sperm motility, and be crucial in sperm function.<\/jats:p>","DOI":"10.3390\/cells12152003","type":"journal-article","created":{"date-parts":[[2023,8,5]],"date-time":"2023-08-05T10:21:39Z","timestamp":1691230899000},"page":"2003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Aquaporin-7-Mediated Glycerol Permeability Is Linked to Human Sperm Motility in Asthenozoospermia and during Sperm Capacitation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-8875","authenticated-orcid":false,"given":"Jo\u00e3o C.","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4050-313 Porto, Portugal"},{"name":"LAQV-REQUIMTE and Department of Chemistry, University of Aveiro, 3010-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1941-6634","authenticated-orcid":false,"given":"Raquel L.","family":"Bernardino","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Ana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Genetics Professor Alberto Barros, 4100-012 Porto, Portugal"}]},{"given":"Alberto","family":"Barros","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Genetics Professor Alberto Barros, 4100-012 Porto, Portugal"},{"name":"Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4666-9546","authenticated-orcid":false,"given":"Giuseppe","family":"Calamita","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-783X","authenticated-orcid":false,"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[{"name":"iBiMED-Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-5699","authenticated-orcid":false,"given":"Pedro F.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE and Department of Chemistry, University of Aveiro, 3010-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1152\/physrev.00017.2015","article-title":"Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility","volume":"96","author":"Skakkebaek","year":"2016","journal-title":"Physiol. 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