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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 (Deltapsi(m)), 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 Deltapsi(m) and mitochondrial membrane integrity because of diminished NADPH, NADH, and GSH. Mitochondria constitute major Ca(2+) stores; thus, diminished mitochondrial mass accounts for reduced Ca(2+) fluxing, defective forward motility, and infertility. Reduced forward progression of TAL-deficient spermatozoa is associated with diminished mitochondrial reactive oxygen intermediate production and Ca(2+) levels, intracellular acidosis, and compensatory down-regulation of carbonic anhydrase IV and overexpression of CD38 and gamma-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.

SUBMITTER: Perl A

PROVIDER: S-EPMC1595434 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa.

Perl Andras A Qian Yueming Y Chohan Kazim R KR Shirley Cynthia R CR Amidon Wendy W Banerjee Sanjay S Middleton Frank A FA Conkrite Karina L KL Barcza Maureen M Gonchoroff Nick N Suarez Susan S SS Banki Katalin K

Proceedings of the National Academy of Sciences of the United States of America 20060926 40

Fertility of spermatozoa depends on maintenance of the mitochondrial transmembrane potential (Deltapsi(m)), 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 Deltapsi(m) and mitochondrial membrane integrity because of d ...[more]

PMID: 17003133

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Project description:BackgroundSpermatogenesis is a complex biological process highlighted by synthesis and activation of proteins that regulate meiosis and cellular differentiation occur during spermatogenesis. 14-3-3 proteins are adaptor proteins that play critical roles in kinase signaling, especially for regulation of cell cycle and apoptosis in eukaryotic cells. There are seven isoforms of the 14-3-3 family proteins encoded by seven genes (β, ε, γ, η, θ/τ, ζ and σ). 14-3-3 isoforms have been shown to have many interacting partners in several tissues including testis.ObjectiveWhile it is known that 14-3-3 proteins are expressed in the functions of testis and spermatozoon, the role for each of the seven isoforms is not known. In this study, we investigated the roles of 14-3-3η and 14-3-3ε isoforms in spermatogenesis.Materials and methodsTo study the in vivo function of 14-3-3η and 14-3-3ε in spermatogenesis, we generated testis-specific and global knockout mice for each of 14-3-3η and 14-3-3ε isoforms (CKO and GKO, respectively). Computer-assisted semen analysis was used to assess sperm motility, while immunohistochemical studies were conducted to check spermatogenesis.ResultsAlthough both 14-3-3η and 14-3-3ε isoforms were present in mouse testis, only the expression of 14-3-3ε, but not 14-3-3η, was detected in spermatozoa. Mice lacking 14-3-3η were normal and fertile while 14-3-3ε CKO and GKO males showed infertility. Low sperm count with higher abnormal spermatozoa was seen in 14-3-3ε CKO mice. The motility of 14-3-3ε knockout spermatozoa was lower than that of the control. A reduction in the phosphorylation of both glycogen synthase kinase 3 and PP1γ2 was also seen in spermatozoa from 14-3-3ε CKO mice, suggesting a specific role of 14-3-3ε in spermatogenesis, sperm motility, and fertility.Discussion and conclusionThis is the first demonstration that of the seven 14-3-3 isoforms, 14-3-3ε is essential for normal sperm function and male fertility.

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Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa.

Publications

Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa.

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