Defective mitochondrial oxidative phosphorylation in varicocele-bearinc testicles

Objectives: Our previous study revealed a decreased blood flow in varicocele-bearing testicles. For further understanding of the possible mechanism of varicocele-induced infertility, we investigated the changes in energy metabolism in varicocele-bearing testicles. Methods: Partial ligation of the left renal vein was performed in 40 Wistar rats to induce dilation of the internal spermatic vein, and sham operations were performed in 20 other age-matched Wistar rats serving as controls. Orchiectomy was done at 1, 2, 4, and 6 months after induction of varicocele (or sham operation) in both groups. The histologic changes in the testicles were evaluated under the light microscope. The concentration of adenine nucleotides was determined by high-performance liquid chromatography, and various enzyme activities of mitochondria were determined by a spectrophotometer. Results: Histologic studies of varicocele-bearing testicles showed a lower Johnsen score (8.5 ± 0.7 versus 9.3 ± 0.5) and a decreased mean testicular tubular diameter (280.0 ± 3.2 versus 295.0 ± 1.4 urn) compared with the testicles in the sham-operated group. The energy charge decreased from 0.71 ± 0.04, 0.70 ± 0.03, 0.69 ± 0.06, and 0.64 ± 0.03 to 0.62 ± 0.08, 0.59 ± 0.05, 0.58 ± 0.05, and 0.56 ± 0.02 at 1, 2, 4, and 6 months, respectively. The reduced nicotinamide-adenine dinucleotide-cytochrome c reductase activities were decreased from 136.6 ± 4.9, 127.3 ± 10.7, 121.6 ± 7.8, and 1 18.9 ± 8.5 to 96.3 ± 13.9, 95.6 ± 27.8, 88.3 ± 13.8, and 80.4 ± 8.7 nmol/min/mg of protein, respectively; the succinatecytochrome c reductase activities were decreased from 50.4 ± 2.7, 49.0 ± 4.7, 49.6 ±7.1, and 42.6 ± 1.6 to 40.3 ± 7.3, 41.0 ± 1 1.5, 40.2 ± 5.7, and 32.0 ± 1.3 nmol/min/mg of protein, respectively; and the cytochrome c oxidase activities were decreased from 361.2 ± 23.4, 350.3 ± 25.5, 223.5 ± 12.9, and 194.1 ± 18.3 to 253.7 ± 32.9,256.4 ± 38.8, 178.2 ± 15.7, and 147.1 ± 17.2 nmol/min/mg of protein at 1, 2, 4, and 6 months, respectively. Conclusions: We thus suggest that defective energy metabolism plays an important role in the impairment of spermatogenesis of varicocele-bearing testicles.