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Aging Cell. 2015 Oct;14(5):887-95. doi: 10.1111/acel.12368. Epub 2015 Jun 26.

Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging.

Author information

1
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
2
TCART Fertility Partners, 150 Bloor W, Toronto, ON, M5S 2X9, Canada.
3
Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
4
Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA.
5
Department of Biology, McGill University, 3649 Promenade Sir William Osler, Montreal, QC, H3G 0B1, Canada.
6
Department of Obstetrics and Gynecology, University of Toronto, 92 College Street, Toronto, ON, M5G 1L4, Canada.
7
LifeQuest Centre for Reproductive Medicine, 655 Bay St, Toronto, ON, M5G 2K4, Canada.
8
Department of Genetics, University of Pennsylvania, 575 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA, 19104-6145, USA.

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.

KEYWORDS:

Mitochondria; anti-aging; fecundity; individual; molecular biology of aging; mouse models

PMID:
26111777
PMCID:
PMC4568976
DOI:
10.1111/acel.12368
[Indexed for MEDLINE]
Free PMC Article

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