The sodium-glucose cotransporter isoform 1 (SGLT-1) is important for sperm energetics, motility, and fertility

• Published in: Biology of reproduction 2022-06, Vol.106 (6), p.1206-1217
• Main Authors: Numata, September, McDermott, Jeff P., Sanchez, Gladis, Mitra, Amrita, Blanco, Gustavo
• Format: Article
• Language: English
• Subjects: acrosomal reaction; Adenosine Triphosphate - metabolism; Animals; energetics; Fertility; Flagella; Glucose; Glucose - metabolism; glucose uptake; Glycolysis; Immunocytochemistry; Isoforms; Male; Mice; Motility; Na+/glucose cotransporter; Na+/K+-exchanging ATPase; Phlorhizin - metabolism; Phlorhizin - pharmacology; Phosphorylation; Protein Isoforms - metabolism; RESEARCH ARTICLE; SGLT; Sodium - metabolism; Sodium - pharmacology; Sodium-Glucose Transporter 1; Sodium-Potassium-Exchanging ATPase - metabolism; Sperm; sperm capacitation; sperm motility; Sperm Motility - physiology; Spermatozoa - metabolism; Tyrosine
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1093/biolre/ioac052

Glucose is a key substrate for supporting sperm energy production and function. Previous studies have demonstrated that sperm glucose uptake is facilitated by several isoforms of the glucose transporters (GLUT). Here, we report that sperm also expresses the Na+-dependent sodium glucose cotransporter (SGLT). This was first suggested by our observation that genetic deletion of the testis-specific Na,K-ATPase α4, which impairs the sperm plasma membrane Na+ gradient, reduces glucose uptake and ATP production. Immunoblot analysis revealed the presence of an SGLT in sperm, with specific expression of isoform 1 (SGLT-1), but not of isoform 2 (SGLT-2). Immunocytochemistry identified SGLT-1 in the mid- and principal piece of the sperm flagellum. Inhibition of SGLT-1 with the isotype-selective inhibitor phlorizin significantly reduced glucose uptake, glycolytic activity, and ATP production in noncapacitated and capacitated sperm from wild-type mice. Phlorizin also decreased total sperm motility, as well as other parameters of sperm movement. In contrast, inhibition of SGLT-1 had no significant effect on sperm hyperactivation, protein tyrosine phosphorylation, or acrosomal reaction. Importantly, phlorizin treatment impaired the fertilizing capacity of sperm. Altogether, these results demonstrate that mouse sperm express a functional SGLT transport system that is important for supporting sperm energy production, motility, and fertility. Summary Sentence The Na+-dependent glucose cotransporter type 1 (SGLT-1) is expressed in mouse spermatozoa and plays an important role in sperm physiology. Graphical Abstract