Isoprenoid pathway dysfunction in human male infertility.

The isoprenoid pathway produces 3 key metabolites: digoxin (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), dolichol (regulates N-glycosylation of proteins), and ubiquinone (free radical scavenger). The pathway was assessed in patients with human male infertility (oligospermia and decreased motility). It was also studied for comparison in patients with right hemispheric, left hemispheric, and bihemispheric dominance. The results of the study showed that the isoprenoid pathway was upregulated with increased digoxin synthesis in all 3 groups of patients. There was also a reduction in membrane Na(+)-K(+) ATPase activity and serum magnesium levels. There was an increase in tryptophan catabolites and a reduction in tyrosine catabolites. The dolichol and glycoconjugate levels increased and lysosomal stability was reduced with increased serum lysosomal enzymes in all 3 groups. The ubiquinone levels were low and free radicals increased. The cholesterol:phospholipid ratio increased and glycoconjugate was reduced in the membrane of these patients. This pattern correlated with those in right hemispheric dominance. The significance of these factors in the pathogenesis of human male infertility is discussed.