title: Human lactate dehydrogenase A (LDHA) rescues mouse Ldhc-null sperm function.
abstract: By targeted disruption of the lactate dehydrogenase c (Ldhc) gene, we demonstrated that spermatozoa require Ldhc for capacitation, motility, and fertilizing capacity. Ldhc expression is restricted to the developing germ cells that, however, are apparently not compromised by the lack of the LDHC isozyme. Because LDHC is abundant in spermatozoa that utilize aerobic glycolysis for energy requirements, its main function was presumed to be the interconversion of pyruvate to lactate with the concomitant oxidation/reduction of NADH to NAD(+). We found that sperm without LDHC were still able to convert lactate to pyruvate as mediated by LDHA that is tightly bound to the fibrous sheath. It was assumed that the level of glycolysis was insufficient to power motility and the subsequent fertilizing capacity of the mutated sperm. To investigate whether LDHC possesses certain unique characteristics essential for fertility, human LDHA was introduced as a transgene to Ldhc-null mice. We report here that the exogenous LDHA rescued the phenotype of the Ldhc-null males. Sperm from the LDHA transgenic males with the Ldhc deletion (LDHA(+)/Ldhc(-/-)) are motile, capable of protein tyrosine phosphorylation, and able to fertilize, thus restoring these properties to LDHC-null sperm. However, the lactate and ATP levels in the rescued sperm did not differ significantly from sperm lacking LDHC. We suggest that it is the localization of the transgene to the sperm cytosol that is mainly responsible for restoration of sperm function and fertility.
authors: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors: Huanghui
authors: H
authors: Tang
authors: Chongwen
authors: C
authors: Duan
authors: Reiner
authors: R
authors: Bleher
authors: Erwin
authors: E
authors: Goldberg
mesh_terms: D000818:Animals; D005260:Female; D005298:Fertility / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007248:Infertility, Male / Q000201:enzymology* / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000080864:Lactate Dehydrogenase 5; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013094:Spermatozoa / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C409673:lactate dehydrogenase C4