LDHC: The Ultimate Testis‐Specific Gene
Open accessAbstract
ABSTRACT: Lactate dehydrogenase C (LDHC) was, to the best of our knowledge, the first testis‐specific isozyme discovered in male germ cells. In fact, this was accomplished shortly before “isozymes or isoenzymes” became a field of study. LDHC was detected initially in human spermatozoa and spermatogenic cells of the testes by gel electrophoresis. Immunohistochemistry was used to localize LDHC first in early‐pachytene primary spermatocytes, with an apparent increase in quantity after meiosis, to its final localization in and on the principal piece of the sperm tail. After several decades of biologic, biochemical, and genetic investigations, we now know that the lactate dehydrogenase isozymes are ubiquitous in vertebrates, developmentally regulated, tissue and cell specific, and multifunctional. Here, we will review the history of LDHC and the work that demonstrates clearly that it is required for sperm to accomplish their ultimate goal, fertilization.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
LDHA and LDHB are widely expressed including brain, while LDHC is restricted to testis and sperm.
“While LDHA and LDHB are widely expressed including brain (Miura, 1966a;Miura, 1966b;Ross et al., 2010), LDHC is restricted to testis and sperm (Goldberg et al., 2010).”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Goldberg et al., 2010
The Tissue localization section confirms LDHC in testis and sperm but says it is not restricted to them: LDHC protein was also detected in oocytes and fertilized eggs through the preimplantation blastocyst stage. The supplied passages do not give a page number. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredLactate can only be synthesized or used in metabolic reactions with the help of lactate dehydrogenase (LDH), a tetramer of LDHA and LDHB subunits in varying compositions.
“lactate can only be synthesized or used in metabolic reactions with the help of lactate dehydrogenase (LDH), a tetramer of LDHA and LDHB subunits in varying compositions.”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Goldberg et al., 2010
In “Discovery of LDHC: The Beginning of a Journey” (page not provided), the paper says LDH catalyzes the interconversion of pyruvate and lactate and describes tetramers assembled from A and B subunits. But that section also identifies LDH-C4, a tetramer of C subunits, so the claim’s description of LDH as composed only of LDHA and LDHB is too narrow. The paper does not establish the claim’s absolute “can only” wording. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn mammals, three Ldh genes give rise to subunits (LDHA, LDHB, LDHC) that form tetrameric LDH isoenzymes.
“In mammals, three Ldh genes give rise to subunits (LDHA, LDHB, LDHC) that form tetrameric LDH isoenzymes.”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Goldberg et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 82
- Alcivar AA Trasler JM Hake LE Salehi-Ashtiani K Goldberg E Hecht NB DNA methylation and expression of the genes coding for lactate dehydrogenases A and C during rodent spermatogenesis Biol Reprod 1991 44 527 535 2015369
- Allen JM Multiple forms of lactic dehydrogenase in tissues of the mouse: their specificity, cellular localization, and response to altered physiological conditions Ann N Y Acad Sci 1961 94 937 951 13860552
- Alvarez JG Storey BT Assessment of cell damage caused by spontaneous lipid peroxidation in rabbit spermatozoa Biol Reprod 1984 30 323 331 6231058
- Beyler SA Wheat TE Goldberg E Binding of antibodies against antigenic domains of murine lactate dehydrogenase-C4 to human and mouse spermatozoa Biol Reprod 1985 32 1201 1210 2410040
- Blanco A Burgos C Gerez de Burgos NM Montamat EE Properties of the testicular lactate dehydrogenase isoenzyme The Biochemical journal 1976 153 165 172 1275882 PMC1172559
- Blanco A Zinkham WH Lactate Dehydrogenases in Human Testes Science 1963 139 601 602 17788300
- Boer PH Adra CN Lau YF McBurney MW The testis-specific phosphoglycerate kinase gene pgk-2 is a recruited retroposon Mol Cell Biol 1987 7 3107 3112 2823118 PMC367943
- Bone W Jones NG Kamp G Yeung CH Cooper TG Effect of ornidazole on fertility of male rats: inhibition of a glycolysis-related motility pattern and zona binding required for fertilization in vitro J Reprod Fertil 2000 118 127 135 10793634
- Bonny C Goldberg E The CpG-rich promoter of human LDH-C is differentially methylated in expressing and nonexpressing tissues Developmental genetics 1995 16 210 217 7736669
- Boussouar F Benahmed M Lactate and energy metabolism in male germ cells Trends Endocrinol Metab 2004 15 345 350 15350607
- Burgos C Maldonado C Gerez de Burgos NM Aoki A Blanco A Intracellular localization of the testicular and sperm-specific lactate dehydrogenase isozyme C4 in mice Biol Reprod 1995 53 84 92 7669861
- Cooker LA Brooke CD Kumari M Hofmann MC Millan JL Goldberg E Genomic structure and promoter activity of the human testis lactate dehydrogenase gene Biol Reprod 1993 48 1309 1319 8318584
- Coonrod S Vitale A Duan C Bristol-Gould S Herr J Goldberg E Testis-specific lactate dehydrogenase (LDH-C4; Ldh3) in murine oocytes and preimplantation embryos J Androl 2006 27 502 509 16582413
- Dewey MM Conklin JL Starch gel electrophoresis of lactic dehydrogenase from rat kidney Proceedings of the Society for Experimental Biology and Medicine Society for Experimental Biology and Medicine 1960 105 492 494 13722398
- Duan C Goldberg E Inhibition of lactate dehydrogenase C4 (LDH-C4) blocks capacitation of mouse sperm in vitro Cytogenet Genome Res 2003 103 352 359 15051959
- Edwards Y West L Van Heyningen V Cowell J Goldberg E Regional localization of the sperm-specific lactate dehydrogenase, LDHC, gene on human chromosome 11 Annals of human genetics 1989 53 215 219 2596827
- Erickson RP Friend DS Tennenbaum D Localization of lactate dehydrogenase-X on the surfaces of mouse spermatozoa Experimental cell research 1975a 91 1 5 1093856
- Erickson RP Stites DP Spielmann H Effects on fertility of immunization against lactate dehydrogenase X in female mice Contraception 1975b 12 333 338 1172463
- Everse J Kaplan NO Lactate dehydrogenases: structure and function Adv Enzymol Relat Areas Mol Biol 1973 37 61 133 4144036
- Fujimoto H Erickson RP Tone S Changes in polyadenylation of lactate dehydrogenase-X mRNA during spermatogenesis in mice Mol Reprod Dev 1988 1 27 34 2908441
- Gavella M Cvitkovic P Semen LDH-X deficiency and male infertility Arch Androl 1985 15 173 176 3833074
- Goldberg E Lactic and Malic Dehydrogenases in Human Spermatozoa Science 1963 139 602 603 17788301
- Goldberg E Lactate Dehydrogenases and Malate Dehydrogenases in Sperm: Studied by Polyacrylamide Gel Electrophoresis Ann N Y Acad Sci 1964 121 560 570 14240552
- Goldberg E Lactate Dehydrogenases in Spermatozoa: Subunit Interactions in Vitro Arch Biochem Biophys 1965 109 134 141 14281937
- Goldberg E Amino acid composition and properties of crystalline lactate dehydrogenase X from mouse testes J Biol Chem 1972 247 2044 2048 4622741
- Goldberg E Infertility in female rabbits immunized with lactate dehydrogenase X Science 1973 181 458 459 4718114
- Goldberg E Lactate dehydrogenase-X from mouse testes and spermatozoa Methods Enzymol 1975 41 318 323 1128270
- Goldberg E Developmental expression of lactate dehydrogenase isozymes during spermatogenesis Prog Clin Biol Res 1990 344 49 52 2203052
- Goldberg E Hawtrey C The ontogeny of sperm specific lactate dehydrogenase in mice J Exp Zool 1967 164 309 316 6068185
- Goldberg E VandeBerg JL Mahony MC Doncel GF Immune response of male baboons to testis-specific LDH-C(4) Contraception 2001 64 93 98 11704085
- Grootegoed JA Jansen R Van der Molen HJ The role of glucose, pyruvate and lactate in ATP production by rat spermatocytes and spermatids Biochim Biophys Acta 1984 767 248 256 6498180
- Hintz M Goldberg E Immunohistochemical localization of LDH-x during spermatogenesis in mouse testes Dev Biol 1977 57 375 384 326599
- Hogrefe HH Griffith JP Rossmann MG Goldberg E Characterization of the antigenic sites on the refined 3-A resolution structure of mouse testicular lactate dehydrogenase C4 J Biol Chem 1987 262 13155 13162 2443489
- Jutte NH Jansen R Grootegoed JA Rommerts FF Clausen OP van der Molen HJ Regulation of survival of rat pachytene spermatocytes by lactate supply from Sertoli cells J Reprod Fertil 1982 65 431 438 6808129
- Krisfalusi M Miki K Magyar PL O’Brien DA Multiple glycolytic enzymes are tightly bound to the fibrous sheath of mouse spermatozoa Biol Reprod 2006 75 270 278 16687649
- Kroft TL Li S Doglio L Goldberg E A transgenic analysis of mouse lactate dehydrogenase C promoter activity in the testis J Androl 2003 24 843 852 14581510
- Li S Zhou W Doglio L Goldberg E Transgenic mice demonstrate a testis-specific promoter for lactate dehydrogenase, LDHC J Biol Chem 1998 273 31191 31194 9813024
- Li SS Lactate dehydrogenase isoenzymes A (muscle), B (heart) and C (testis) of mammals and the genes coding for these enzymes Biochemical Society transactions 1989 17 304 307 2753209
- Li SS Feldmann RJ Okabe M Pan YC Molecular features and immunological properties of lactate dehydrogenase C4 isozymes from mouse and rat testes J Biol Chem 1983a 258 7017 7028 6189833
- Li SS Fitch WM Pan YC Sharief FS Evolutionary relationships of vertebrate lactate dehydrogenase isozymes A4 (muscle), B4 (heart), and C4 (testis) J Biol Chem 1983b 258 7029 7032 6853510
- Li SS O’Brien DA Hou EW Versola J Rockett DL Eddy EM Differential activity and synthesis of lactate dehydrogenase isozymes A (muscle), B (heart), and C (testis) in mouse spermatogenic cells Biol Reprod 1989 40 173 180 2923949
- Li YJ Tsoi SC Mannen H Shoei-lung Li S Phylogenetic analysis of vertebrate lactate dehydrogenase (LDH) multigene families Journal of molecular evolution 2002 54 614 624 11965434
- Mahi-Brown CA VandeVoort CA McGuinness RP Overstreet JW O’Hern P Goldberg E Immunization of male but not female mice with the sperm-specific isozyme of lactate dehydrogenase (LDH-C4) impairs fertilization in vivo Am J Reprod Immunol 1990 24 1 8 2285453
- Mannen H Tsoi SC Krushkal JS Li WH Li SS The cDNA cloning and molecular evolution of reptile and pigeon lactate dehydrogenase isozymes Molecular biology and evolution 1997 14 1081 1087 9364765
- Markert CL Amet TM Goldberg E Human testis-specific lactate dehydrogenase-C promoter drives overexpression of mouse lactate dehydrogenase-1 cDNA in testes of transgenic mice J Exp Zool 1998 282 171 178 9723174
- Markert CL Appella E Physicochemical nature of isozvmes Ann N Y Acad Sci 1961 94 678 690 14469961
- Markert CL Shaklee JB Whitt GS Evolution of a gene. Multiple genes for LDH isozymes provide a model of the evolution of gene structure, function and regulation Science 1975 189 102 114 1138367
- McCarrey JR Thomas K Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene Nature 1987 326 501 505 3453121
- Miki K Energy metabolism and sperm function Soc Reprod Fertil Suppl 2007 65 309 325 17644971
- Miki K Qu W Goulding EH Willis WD Bunch DO Strader LF Perreault SD Eddy EM O’Brien DA Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility Proc Natl Acad Sci U S A 2004 101 16501 16506 15546993 PMC534542
- Millan JL Driscoll CE LeVan KM Goldberg E Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence Proc Natl Acad Sci U S A 1987 84 5311 5315 2440048 PMC298845
- Mita M Hall PF Metabolism of round spermatids from rats: lactate as the preferred substrate Biol Reprod 1982 26 445 455 7082719
- Montamat EE Vermouth NT Blanco A Subcellular localization of branched-chain amino acid aminotransferase and lactate dehydrogenase C4 in rat and mouse spermatozoa The Biochemical journal 1988 255 1053 1056 3214422 PMC1135348
- Mukai C Okuno M Glycolysis plays a major role for adenosine triphosphate supplementation in mouse sperm flagellar movement Biol Reprod 2004 71 540 547 15084484
- Musick WD Rossmann MG The structure of mouse testicular lactate dehydrogenase isoenzyme C4 at 2.9 A resolution J Biol Chem 1979 254 7611 7620 468772
- O’Hern PA Bambra CS Isahakia M Goldberg E Reversible contraception in female baboons immunized with a synthetic epitope of sperm-specific lactate dehydrogenase Biol Reprod 1995 52 331 339 7536050
- Oakes CC La Salle S Smiraglia DJ Robaire B Trasler JM A unique configuration of genome-wide DNA methylation patterns in the testis Proc Natl Acad Sci U S A 2007 104 228 233 17190809 PMC1765440
- Odet F Duan C Willis WD Goulding EH Kung A Eddy EM Goldberg E Expression of the Gene for Mouse Lactate Dehydrogenase C (Ldhc) Is Required for Male Fertility Biol Reprod 2008 79 1 26 34 18367675 PMC2574787
- Olsson PG Tsujioka H Narisawa S Goldberg E Millan JL Abundance of repetitive sequence elements in the mouse testis-specific lactate dehydrogenase-C gene J Androl 2003 24 918 920 14581519
- Orlando C Casano R Caldini AL Forti G Barni T Bonfanti L Serio M Measurement of seminal LDH-X and transferrin in normal and infertile men J Androl 1988 9 220 223 3403363
- Pan YC Sharief FS Okabe M Huang S Li SS Amino acid sequence studies on lactate dehydrogenase C4 isozymes from mouse and rat testes J Biol Chem 1983 258 7005 7016 6343385
- Roller RJ Kinloch RA Hiraoka BY Li SS Wassarman PM Gene expression during mammalian oogenesis and early embryogenesis: quantification of three messenger RNAs abundant in fully grown mouse oocytes Development 1989 106 251 261 2591314
- Salehi-Ashtiani K Goldberg E Posttranscriptional regulation of primate Ldhc mRNA by its AUUUA-like elements Mol Endocrinol 1995 9 1782 1790 8614414
- Shima JE McLean DJ McCarrey JR Griswold MD The murine testicular transcriptome: characterizing gene expression in the testis during the progression of spermatogenesis Biol Reprod 2004 71 319 330 15028632
- Sleight SB Miranda PV Plaskett NW Maier B Lysiak J Scrable H Herr JC Visconti PE Isolation and proteomic analysis of mouse sperm detergent-resistant membrane fractions: evidence for dissociation of lipid rafts during capacitation Biol Reprod 2005 73 721 729 15917346
- Smithies O Zone electrophoresis in starch gels and its application to studies of serum proteins Advances in protein chemistry 1959 14 65 113 13832188
- Takeno T Li SS Structure of the human lactate dehydrogenase B gene The Biochemical journal 1989 257 921 924 2930497 PMC1135676
- Tang H Goldberg E Homo sapiens lactate dehydrogenase c (Ldhc) gene expression in cancer cells is regulated by transcription factor Sp1, CREB, and CpG island methylation J Androl 2009 30 157 167 18930904
- Tang H Kung A Goldberg E Regulation of murine lactate dehydrogenase C (Ldhc) gene expression Biol Reprod 2008 78 455 461 18057313 PMC2311504
- Thomas K Del Mazo J Eversole P Bellve A Hiraoka Y Li SS Simon M Developmental regulation of expression of the lactate dehydrogenase (LDH) multigene family during mouse spermatogenesis Development 1990 109 483 493 2401207
- Travis AJ Jorgez CJ Merdiushev T Jones BH Dess DM Diaz-Cueto L Storey BT Kopf GS Moss SB Functional relationships between capacitation-dependent cell signaling and compartmentalized metabolic pathways in murine spermatozoa J Biol Chem 2001 276 7630 7636 11115497
- Urner F Leppens-Luisier G Sakkas D Protein tyrosine phosphorylation in sperm during gamete interaction in the mouse: the influence of glucose Biol Reprod 2001 64 1350 1357 11319138
- Urner F Sakkas D Glucose participates in sperm-oocyte fusion in the mouse Biol Reprod 1996 55 917 922 8879509
- Urner F Sakkas D Protein phosphorylation in mammalian spermatozoa Reproduction 2003 125 17 26 12622692
- Welch JE Brown PL O’Brien DA Magyar PL Bunch DO Mori C Eddy EM Human glyceraldehyde 3-phosphate dehydrogenase-2 gene is expressed specifically in spermatogenic cells J Androl 2000 21 328 338 10714828
- Welch JE Schatte EC O’Brien DA Eddy EM Expression of a glyceraldehyde 3-phosphate dehydrogenase gene specific to mouse spermatogenic cells Biol Reprod 1992 46 869 878 1375514
- Wheat TE Goldberg E Immunochemical dissection of the testes-specific isozyme lactate dehydrogenase C4 Ann N Y Acad Sci 1984 438 156 170 6085454
- Williams AC Ford WC The role of glucose in supporting motility and capacitation in human spermatozoa J Androl 2001 22 680 695 11451366
- Zamudio NM Chong S O’Bryan MK Epigenetic regulation in male germ cells Reproduction 2008 136 131 146 18515312
- Zhou W Xu J Goldberg E A 60-bp core promoter sequence of murine lactate dehydrogenase C is sufficient to direct testis-specific transcription in vitro Biol Reprod 1994 51 425 432 7803614
- Zinkham WH Blanco A Clowry LJ Jr An Unusual Isozyme of Lactate Dehydrogenase in Mature Testes: Localization, Ontogeny, and Kinetic Properties Ann N Y Acad Sci 1964 121 571 588 14240553
- Zinkham WH Isensee H Renwick JH Linkage of lactate dehydrogenase B and C loci in pigeons Science 1969 164 185 187 5774192
Cited by
Sorted by citations
Czyż, D. M., Willett, J. W., & Crosson, S. (2017) · Journal of Bacteriology · doi:10.1128/jb.00227-17 · Cited by 87 · see citing works
Späte, E., Zhou, B., Sun, T., Kusch, K., Asadollahi, E., Siems, S. B., Depp, C., Werner, H. B., Saher, G., Hirrlinger, J., et al. (2024) · Glia · doi:10.1002/glia.24533 · Cited by 40 · see citing works
- Authors
- Goldberg, E., Eddy, E. M., Duan, C., & Odet, F.
- Affiliations
- Northwestern University (US)
- National Institutes of Health (US)
- Corresponding author
- Goldberg, Erwin
- Venue
- Journal of Andrology
- Publisher
- Wiley
- Published
- 2010-01-02
- Volume
- 31
- Issue
- 1
- Pages
- 86-94
- ISSN
- 0196-3635 (ISSN-L)
- 1939-4640
- PMC
- PMC2915756
- OpenAlex
- W2022917308
- Cited by
- 148
- References
- 0
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 8 · 2023: 4 · 2022: 17 · 2021: 12 · 2020: 16 · 2019: 5 · 2018: 4 · 2017: 10 · 2016: 8 · 2015: 8 · 2014: 9 · 2013: 7 · 2012: 10
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Andrology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (Z01ES070076)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD005863, HD 05863)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Reproductive biology and impacts on aquatic species
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- lactate dehydrogenase C, testis-specific genes, male germ cells, spermatozoa, spermatogenesis, sperm flagellum, isozymes, fertilisation (biology)
- MeSH terms
- Animals, Humans, Isoenzymes, L-Lactate Dehydrogenase, Male, Spermatozoa, Testis, Gene Expression Regulation, Developmental
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
