Glyceraldehyde 3-phosphate dehydrogenase-S protein distribution during mouse spermatogenesis

Bunch, Donna O.

doi:10.1095/biolreprod58.3.834

Cited by 145 publications

(136 citation statements)

References 69 publications

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“…1E). The lack of enzymatic activity in sperm from Gapds Ϫ/Ϫ males verified previous immunocytochemical results indicating that the somatic GAPDH isozyme is not present in sperm (4,5). The block in glycolysis at the reaction catalyzed by GAPDS resulted in a 4-fold accumulation of the substrate, glyceraldehyde 3-phosphate, in sperm from Gapds Ϫ/Ϫ mice Values are means Ϯ SEM.…”

Section: Sperm Glycolysis Is Blocked By the Targeted Deletion Of Gapdssupporting

confidence: 87%

“…Previous studies detected only the germ cell-specific GAPDS͞ GAPD2 isozyme in both mouse and human sperm (4,5). Because this enzyme precedes both ATP-generating steps in glycolysis, elimination of GAPDS activity should block all glycolytic ATP production in sperm (Fig.…”

Section: Sperm Glycolysis Is Blocked By the Targeted Deletion Of Gapdsmentioning

confidence: 95%

“…Testes were fixed in Bouin's solution, dehydrated, and embedded in paraffin (4). Sections were stained with hematoxylin͞eosin for histological analysis.…”

Section: Gapds Enzyme Activitymentioning

confidence: 99%

“…Oxidative phosphorylation is confined to the proximal segment of the flagellum where the mitochondria are localized (middle piece). In contrast, glycolysis appears to be restricted to the principal piece, which is distal to the middle piece and is the longest segment of the sperm flagellum (4)(5)(6)(7)(8). Several glycolytic enzymes in mammalian sperm are distinct from the isozymes present in somatic tissues.…”

mentioning

confidence: 99%

“…Several glycolytic enzymes in mammalian sperm are distinct from the isozymes present in somatic tissues. Three isozymes, glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS), phosphoglycerate kinase-2, and lactate dehydrogenase-C 4 , are encoded by paralogous genes expressed only during spermatogenesis (5,(9)(10)(11)(12)(13). At least five other enzymes in the glycolytic pathway have unique structural or functional properties in spermatogenic cells (6,(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

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

Miki

Goulding

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

551

457

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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. glycolysis ͉ gene targeting ͉ infertility S perm motility is essential for normal fertilization, and asthenozoospermia, or low sperm motility, is common in infertile men. In a recent study of 1,085 sperm samples from infertile men, 81% had defects in motility, and 19% had asthenozoospermia without other defects in sperm number or morphology (1). Motility is generated by the extremely long flagellum that comprises Ͼ90% of the length of a mammalian sperm. This process requires substantial ATP to support coordinated movement of the central axoneme and surrounding flagellar structures (2). ATP is hydrolyzed by dynein ATPases, which function as force-generating molecular motors along the axoneme. Although quiescent in the epididymis, mammalian sperm display vigorous forward movement, termed activated or progressive motility, immediately upon ejaculation or collection into physiological medium. The motility waveform changes in the female reproductive tract, with increases in both the amplitude and asymmetry of flagellar bending. These changes result in a whiplash-like motion, termed hyperactivated motility, which facilitates sperm transport in the oviduct and penetration of the zona pellucida surrounding the oocyte (3).Potential sources of ATP to support sperm motility are compartmentalized in distinct regions along the length of the flagellum. Oxidative phosphorylation is confined to the proximal segment of the flagellum where the mitochondria are localized (middle piece). In contrast, glycolysis appears to be restricted to the principal piece, which is distal to the middle piece and is the longest segment of the sperm flagellum (4-8). Several glycolytic enzymes in mammalian sperm are distinct from the isozymes present in somatic tissues. Thr...

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Section: Sperm Glycolysis Is Blocked By the Targeted Deletion Of Gapdssupporting

confidence: 87%

Section: Sperm Glycolysis Is Blocked By the Targeted Deletion Of Gapdsmentioning

confidence: 95%

“…Testes were fixed in Bouin's solution, dehydrated, and embedded in paraffin (4). Sections were stained with hematoxylin͞eosin for histological analysis.…”

Section: Gapds Enzyme Activitymentioning

confidence: 99%

mentioning

confidence: 99%