title: Testicular lactate content is compromised in men with Klinefelter Syndrome.
abstract: Klinefelter syndrome (KS) is the most common genetic cause of human infertility, but the mechanism(s) responsible for its phenotype remain largely unknown. KS is associated with alterations in body composition and with a higher risk of developing metabolic diseases. We therefore hypothesized that KS men seeking fertility treatment possess an altered testicular metabolism profile that may hamper the nutritional support of spermatogenesis. Testicular biopsies from control (46, XY) (n = 6) and KS (47, XXY) (n = 6) individuals were collected and analyzed by proton high-resolution magic-angle spinning nuclear magnetic resonance spectroscopy. The mRNA and protein expression of crucial glycolysis-associated enzymes and transporters were evaluated in parallel by quantitative PCR and Western blot, respectively. Our data revealed altered regulation of glucose transporters (GLUT1 and GLUT3); phosphofructokinase 1, liver isoform (PFKL); and lactate dehydrogenase A (LDHA) expression in the testis of KS patients. Moreover, we detected a severe reduction in lactate and creatine accumulation within testicular tissue from KS men. The aberrant levels of the biomarkers detected in testicular biopsies of KS men may therefore be associated with the infertility phenotypes presented by these men. Mol. Reprod. Dev. 83: 208-216, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, 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, Porto, Portugal.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Martins
authors.affiliation: Centre for Research in Ceramics and Composite Materials (CICECO), University of Aveiro, Aveiro, Portugal.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jarak
authors.affiliation: Centre for Reproductive Genetics Professor Alberto Barros, Porto, Portugal.|Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.|I3S - Institute of Health Research and Innovation, University of Porto, Porto, Portugal.
authors.forename: Alberto
authors.initials: A
authors.lastname: Barros
authors.affiliation: Centre for Reproductive Genetics Professor Alberto Barros, Porto, Portugal.
authors.forename: Joaquina
authors.initials: J
authors.lastname: Silva
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, Porto, Portugal.|Centre for Reproductive Genetics Professor Alberto Barros, Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Sousa
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, Porto, Portugal.|I3S - Institute of Health Research and Innovation, University of Porto, Porto, Portugal.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Oliveira
mesh_terms: D000328:Adult; D003404:Creatinine / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007713:Klinefelter Syndrome / Q000378:metabolism* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D025501:Phosphofructokinase-1, Liver Type / Q000378:metabolism; D013737:Testis / Q000378:metabolism* / Q000473:pathology
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D007527:Isoenzymes; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; D019344:Lactic Acid; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D025501:Phosphofructokinase-1, Liver Type