Biochemical markers of early and late spermatogenesis: relationship between the lactate dehydrogenase-X and creatine kinase-M isoform concentrations in human spermatozoa.
As part of our research program on biochemical markers of sperm maturity, we have studied sperm creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations and the isoform ratios of the CK-M [% CK-M/(CK-M + CK-B)] and LDH-X [% LDH-X/(LDH-X + LDH-a)] in 50 oligospermic and 95 normospermic men [corrected]. Because the synthesis of LDH-X is initiated in early spermatogenesis, and that of CK-M commences in late spermiogenesis simultaneously with cytoplasmic extrusion, we proposed two working hypotheses:(1) LDH and CK concentrations reflect the retained cytoplasm in sperm, thus the activities of both enzymes will be related and will be higher in oligospermic specimens, which have a higher incidence of immature spermatozoa; and (2) because in normally developed sperm both LDH-X and CK-M are present, there will be a correlation between LDH-X and CK-M ratios in the mature sperm populations. However, among men with immature sperm samples with late spermiogenetic defect and diminished CK-M ratios, there will be two groups: one which completed spermatogenesis prior to spermiogenetic failure (normal LDH-X and diminished CK-M ratios), and another group with defects in both spermatogenesis and spermiogenesis (low LDH-X and diminished CK-M ratios). Because of this heterogeneity, LDH-X ratios will be a poor predictor of sperm maturity. The data support the hypotheses: (1) LDH and CK concentrations were higher in oligospermic vs. normospermic men (P < 0.001). (2) The LDH and CK concentrations were related (r = 0.65, P < 0.001, N = 145), and there were inverse correlations between CK, LDH, LDH-X, or CK-M ratios vs. sperm concentrations (P < 0.001 in all four). (3) The CK-M and LDH-X ratios were different between the oligospermic and normospermic groups (P < 0.001), although the means of the LDH-X ratios were narrower (LDH-X:1:1.3; CK-M:1:1.9). (4) Dividing the 145 samples by the cut-off value of mean minus 1 SD of the CK-M and LDH-X ratios (11% and 32%, respectively) demonstrated that the CK-M ratios discriminated better than LDH-X ratios between the samples with mature and immature sperm. These data on the biochemical markers of early and late spermatogenesis support the studies in which CK better reflected sperm quality than LDH or LDH-X (Orlando et al., 1994: Int J Androl 17:13-18) and the > 10% sperm CK-M ratio predicted with a rate of 30.4% per cycle in the occurrence of pregnancies in a blinded study of 84 IVF couples (Huszar et al., 1992: Fertil Steril 57:882-888).
Lalwani
S
S
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA.
Sayme
N
N
Vigue
L
L
Corrales
M
M
Huszar
G
G
D015415:Biomarkers; D003402:Creatine Kinase / Q000032:analysis*; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000032:analysis*; D008297:Male; D009845:Oligospermia / Q000201:enzymology; D013091:Spermatogenesis; D013094:Spermatozoa / Q000201:enzymology*
D015415:Biomarkers; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase