ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 S14.4

Targeted disruption of Slc2a8 (GLUT8) reduces ATP levels and mitochondrial potential of spermatozoa

Verena Gawlik1, Stefan Schmidt1, Andrea Scheepers1, Gunther Wennemuth2,3, Robert Augustin1, Markus Moser4, Hadi Al-Hasani1, Hans-Georg Joost1 & Annette Schürmann1

1Department of Pharmacology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany; 2Department of Anatomy and Cell Biology, Philipps-University, Marburg, Germany; 3Department of Anatomy and Cell Biology, Saarland University, Homburg, Germany; 4Max-Planck-Institute of Biochemistry, Martinsreid, Germany.

GLUT8 is a class 3 sugar transport facilitator, and transports glucose with high affinity (km~2 mM). GLUT8 mRNA is expressed in brain, heart, skeletal muscle, adipose tissue, adrenal gland, liver and at particulary high levels in testis. In testis, the GLUT8 protein is located in an intracellular compartment of spermatocytes, spermatids and mature spermatozoa. GLUT8 contains an N-terminal dileucine sorting signal retaining the transporter in an intracellular compartment. So far a stimulus inducing translocation of the transporter to the plasma membrane has not been found. Therefore, a function for GLUT8 in intracellular compartments rather than at the plasma membrane is considered. In order to investigate the physiological role of GLUT8, the corresponding Slc2a8 gene was disrupted in mice. Slc2a8 knockout mice are viable and appeared healthy. Body weight gain and body composition did not differ between Slc2a8 knockout and wild-type mice. Analysis of the offspring distribution of heterozygous matings indicated a lower number of Slc2a8 knockout progeny (30.5: 47.5: 22%, Slc2a8+/+, Slc2a8+/−, and Slc2a8−/− mice, respectively) resulting in a significant deviation (P<0.0024) from the expected Mendelian distribution. This difference was associated with a significant reduction of ATP levels (0.39±0.11 vs 0.78±0.15 μM/μg protein) and mitochondrial membrane potential (42±4.06 vs 57.3±3.03% orange JC-1 fluorescense). In addition number of motile sperm cells was markedly reduced (31±2.26 vs 60.25±2.09%) in Slc2a8 knockout as compared with wild-type spermatozoa. In contrast, sperm number, epidydimal maturation, survival rate, intracellular Ca2+ levels and glucose uptake were not altered in spermatozoa of Slc2a8−/− mice. These data indicate that GLUT8 plays a role in energy metabolism of sperm cells.

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