Coenzyme Q-dependent mitochondrial respiratory chain activity in granulosa cells is reduced with aging

Abstract

Objective: To examine coenzyme Q10 (CoQ10)-dependent mitochondrial respiratory chain (MRC) activity in granulosa cells (GC) with aging and examine the effect of in vitro CoQ supplementation.

Design: Experimental study.

Setting: Hospital laboratory.

Patient(s): Ten younger (<32 years) and 10 older (>39 years) patients undergoing in vitro fertilization (IVF) treatment.

Intervention(s): Measurement of succinate-cytochrome c reductase (MRC complex II + III) activity in the presence and absence of CoQ1 (a soluble CoQ analog).

Main outcome measure(s): MRC enzymatic activity in human GC via complex II + III measured in GC homogenate by spectrophotometry and compared with CoQ in dependent MRC complex II and citrate synthase (CS).

Result(s): Complex II + III activity was 1.9 times higher in young patients compared with older patients (18.3 ± 5.8 and 9.6 ± 3 nmol/min/mg, respectively) whereas II and CS were not statistically significantly different. Increased II + III activity in the presence CoQ1 was observed in both groups but was statistically significantly higher in the older patients, reaching similar levels. Compared with baseline (II + III + Q/II + III), the increase was 2.47 times higher in older patients compared with young patients (6.5 ± 2.0 and 2.62 ± 0.83, respectively).

Conclusion(s): Coenzyme Q10-dependent MRC activity in GC reduces with aging. This reduction is diminished upon in vitro CoQ1 supplementation, indicating that CoQ10 deficit is the underlying cause for the mitochondrial dysfunction. The results show that functional CoQ10 status can be assessed by measuring complex II + III activity in GC and might provide a useful monitoring tool for future clinical studies of oral CoQ10 supplementation to older patients undergoing IVF treatment.

Keywords: Coenzyme Q10; granulosa cells; mitochondria; reproductive aging.