Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging

Aging Cell

Assaf Ben-Meir³  Eliezer Burstein³  Aluet Borrego-Alvarez³  Jasmine Chong³  Ellen Wong³  Tetyana Yavorska³  Taline Naranian³  Maggie Chi⁶  Ying Wang⁴  Yaakov Bentov⁵  Jennifer Alexis¹  James Meriano¹  Hoon-Ki Sung³  David L. Gasser²  Kelle H. Moley⁶  Siegfried Hekimi⁴  Robert F. Casper³ 

[1] LifeQuest Centre for Reproductive Medicine, Toronto, ON, Canada;Department of Genetics, University of Pennsylvania, Philadelphia, PA, 19104-6145, USA;Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada;Department of Biology, McGill University, Montreal, QC, Canada;TCART Fertility Partners, Toronto, ON, Canada;Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, MO, USA

关键词: Mitochondria;    mouse models;    molecular biology of aging;    individual;    fecundity;    anti‐aging;   

DOI  :  10.1111/acel.12368

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.