• PMID: 15546993
• Gene Name: GAPDHS
• Condition: Required for sperm motility and male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Required for sperm motility and male infertility

Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility

Miki K, Qu W, Goulding EH, Willis WD, Bunch DO, Strader LF, Perreault SD, Eddy EM, O'Brien DA.

Although glycolysis is highly conserved, it is remarkable that several unique isozymes in this central metabolic pathway are found in mammalian sperm. Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS) is the product of a mouse gene expressed only during spermatogenesis and, like its human ortholog (GAPD2), is the sole GAPDH isozyme in sperm. It is tightly bound to the fibrous sheath, a cytoskeletal structure that extends most of the length of the sperm flagellum. We disrupted Gapds expression by gene targeting to selectively block sperm glycolysis and assess its relative importance for in vivo sperm function. Gapds(-/-) males were infertile and had profound defects in sperm motility, exhibiting sluggish movement without forward progression. Although mitochondrial oxygen consumption was unchanged, sperm from Gapds(-/-) mice had ATP levels that were only 10.4% of those in sperm from WT mice. These results imply that most of the energy required for sperm motility is generated by glycolysis rather than oxidative phosphorylation. Furthermore, the critical role of glycolysis in sperm and its dependence on this sperm-specific enzyme suggest that GAPDS is a potential contraceptive target, and that mutations or environmental agents that disrupt its activity could lead to male infertility. FAU - Miki, Kiyoshi AU - Miki K AD - Laboratories for Reproductive Biology, and Department of Cell and Developmental Biology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. FAU - Qu, Weidong AU - Qu W FAU - Goulding, Eugenia H AU - Goulding EH FAU - Willis, William D AU - Willis WD FAU - Bunch, Donna O AU - Bunch DO FAU - Strader, Lillian F AU - Strader LF FAU - Perreault, Sally D AU - Perreault SD FAU - Eddy, Edward M AU - Eddy EM