title: Dose-dependent effects of caffeine in human Sertoli cells metabolism and oxidative profile: relevance for male fertility.
abstract: Caffeine is a widely consumed substance present in several beverages. There is an increasing consumption of energetic drinks, rich in caffeine, among young individuals in reproductive age. Caffeine has been described as a modulator of cellular metabolism. Hence, we hypothesized that it alters human Sertoli cells (hSCs) metabolism and oxidative profile, which are essential for spermatogenesis. For that purpose, hSCs were cultured with increasing doses of caffeine (5, 50, 500 μM). Caffeine at the lowest concentrations (5 and 50 μM) stimulated lactate production, but only hSCs exposed to 50 μM showed increased expression of glucose transporters (GLUTs). At the highest concentration (500 μM), caffeine stimulated LDH activity to sustain lactate production. Notably, the antioxidant capacity of hSCs decreased in a dose-dependent manner and SCs exposed to 500 μM caffeine presented a pro-oxidant potential, with a concurrent increase of protein oxidative damage. Hence, moderate consumption of caffeine appears to be safe to male reproductive health since it stimulates lactate production by SCs, which can promote germ cells survival. Nevertheless, caution should be taken by heavy consumers of energetic beverages and food supplemented with caffeine to avoid deleterious effects in hSCs functioning and thus, abnormal spermatogenesis.
authors.affiliation: CICS - UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal.
authors.forename: Tânia R
authors.initials: TR
authors.lastname: Dias
authors.affiliation: CICS - UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Portugal.
authors.forename: Raquel L
authors.initials: RL
authors.lastname: Bernardino
authors.affiliation: CICS - UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Portugal.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Martins
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Moreira
authors.affiliation: Centre for Reproductive Genetics Alberto Barros, 4100-009 Porto, Portugal.
authors.forename: Joaquina
authors.initials: J
authors.lastname: Silva
authors.affiliation: Centre for Reproductive Genetics Alberto Barros, 4100-009 Porto, Portugal; Department of Genetics, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
authors.forename: Alberto
authors.initials: A
authors.lastname: Barros
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Portugal; Centre for Reproductive Genetics Alberto Barros, 4100-009 Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Sousa
authors.affiliation: CICS - UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal. Electronic address: bmcms@ubi.pt.
authors.forename: Branca M
authors.initials: BM
authors.lastname: Silva
authors.affiliation: CICS - UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Portugal. Electronic address: pfobox@gmail.com.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Oliveira
mesh_terms: D002110:Caffeine / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation; D005298:Fertility / Q000187:drug effects*; D051246:Glucose Transport Proteins, Facilitative / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010732:Phosphofructokinase-1 / Q000378:metabolism; D018570:Risk Assessment; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D019344:Lactic Acid; D002110:Caffeine; D007770:L-Lactate Dehydrogenase; D010732:Phosphofructokinase-1
keywords: Caffeine; Cell metabolism; Lactate; Male fertility; Sertoli cell; Spermatogenesis