Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging

Abstract

Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age-related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri-phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age-related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte-specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte-specific Pdss2-deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age-associated oocyte deficits causing infertility.

Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage?

“…In addition, increase in ratio of gametes which are able to support normal development was observed [34]. A controlled randomised trial designed by Bentov et al evaluated the effect of CoQ10 on post-meiotic oocyte aneuploidy rate in women undergoing IVF, finding that the rate of aneuploidy and clinical pregnancy were, respectively, 46.5 and 33 % in the CoQ10 group and 62.8 and 26.7 % in the control group [35].…”

An Application of NGS for Molecular Investigations in Perrault Syndrome: Study of 14 Families and Review of the Literature

“…Mutations in other genes with mitochondrial roles have also been found to be implicated in isolated or syndromic primary ovarian failure [Bekheirnia et al., ; Brauner et al., ; Zhen et al., ]. Moreover, ovarian aging might be accompanied with mitochondrial dysfunction [Ben‐Meir et al., ]. Isolated and syndromic deafness can be due to either mutations in mitochondrial DNA or mutations in nuclear genes coding for mitochondrial proteins [Gutierrez et al, ; Leveque et al., ].…”

Biochemistry of Mitochondrial Coenzyme Q Biosynthesis

“…Exogenous CoQ is efficiently taken up by liver [174, 175], ovarian [176], and brown adipose tissues [177]. However, tissues commonly disrupted by CoQ deficiency, such as the brain and muscle (Box 2), poorly uptake CoQ [178] (Figure IA).…”