Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa
Abstract
Fertility of spermatozoa depends on maintenance of the mitochondrial transmembrane potential (Δψm), which is generated by the electron-transport chain and regulated by an oxidation-reduction equilibrium of reactive oxygen intermediates, pyridine nucleotides, and glutathione (GSH). Here, we report that male mice lacking transaldolase (TAL)-/- are sterile because of defective forward motility. TAL-/- spermatozoa show loss of Δψm and mitochondrial membrane integrity because of diminished NADPH, NADH, and GSH. Mitochondria constitute major Ca2+ stores; thus, diminished mitochondrial mass accounts for reduced Ca2+ fluxing, defective forward motility, and infertility. Reduced forward progression of TAL-deficient spermatozoa is associated with diminished mitochondrial reactive oxygen intermediate production and Ca2+ levels, intracellular acidosis, and compensatory down-regulation of carbonic anhydrase IV and overexpression of CD38 and γ-glutamyl transferase. Microarray analyses of gene expression in the testis, caput, and cauda epididymidis of TAL+/+, TAL+/-, and TAL-/- littermates confirmed a dominant impact of TAL deficiency on late stages of sperm-cell development, affecting the electron-transport chain and GSH metabolism. Stimulation of de novo GSH synthesis by oral N-acetyl-cysteine normalized the low fertility rate of TAL+/- males without affecting the sterility of TAL-/- males. Whereas TAL-/- sperm failed to fertilize TAL+/+ oocytes in vitro, sterility of TAL-/- sperm was circumvented by intracytoplasmic sperm injection, indicating that TAL deficiency influenced the structure and function of mitochondria without compromising the nucleus and DNA integrity. Collectively, these data reveal an essential role of TAL in sperm-cell mitochondrial function and, thus, male fertility.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- October 2006
- DOI:
- 10.1073/pnas.0602678103
- Bibcode:
- 2006PNAS..10314813P
- Keywords:
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- BIOLOGICAL SCIENCES / CELL BIOLOGY