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This Article Full Text Full Text (PDF) [Supplemental Data] All Versions of this Article: 79/1/26    most recent biolreprod.108.068353v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Odet, F. Articles by Goldberg, E. PubMed PubMed Citation Articles by Odet, F. Articles by Goldberg, E. Agricola Articles by Odet, F. Articles by Goldberg, E.

Expression of the Gene for Mouse Lactate Dehydrogenase C (Ldhc) Is Required for Male Fertility¹

Laboratory of Reproductive and Developmental Toxicology,⁴ National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, North Carolina 27709 Department of Biochemistry, Molecular Biology, and Cell Biology,⁵ Northwestern University, Evanston, Illinois 60208

ABSTRACT

The lactate dehydrogenase (LDH) protein family members characteristically are distributed in tissue- and cell type-specific patterns and serve as the terminal enzyme of glycolysis, catalyzing reversible oxidation reduction between pyruvate and lactate. They are present as tetramers, and one family member, LDHC, is abundant in spermatocytes, spermatids, and sperm, but also is found in modest amounts in oocytes. We disrupted the Ldhc gene to determine whether LDHC is required for spermatogenesis, oogenesis, and/or sperm and egg function. The targeted disruption of Ldhc severely impaired fertility in male Ldhc^–/– mice but not in female Ldhc^–/– mice. Testis and sperm morphology and sperm production appeared to be normal. However, total LDH enzymatic activity was considerably lower in Ldhc^–/– sperm than in wild type sperm, indicating that the LDHC homotetramer (LDH-C₄) is responsible for most of the LDH activity in sperm. Although initially motile when isolated, there was a more rapid reduction in the level of ATP and in motility in Ldhc^–/– sperm than in wild-type sperm. Moreover, Ldhc^–/– sperm did not acquire hyperactivated motility, were unable to penetrate the zona pellucida in vitro, and failed to undergo the phosphorylation events characteristic of capacitation. These studies showed that LDHC plays an essential role in maintenance of the processes of glycolysis and ATP production in the flagellum that are required for male fertility and sperm function.

capacitation, fertilization, gamete biology sperm, gene targeting, glycolysis, mouse, sperm capacitation, sperm motility and transport, testis

³These authors contributed equally to this work.

¹Supported in part by NIH HD05863 to E.G., and in part by the Intramural Research Program of the NIH, National Institutes of Environmental Health Sciences to E.M.E.

Correspondence: ²E. Goldberg, Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208. FAX: 847 467 1380; e-mail: erv{at}northwestern.edu