title: 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.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|TCART Fertility Partners, 150 Bloor W, Toronto, ON, M5S 2X9, Canada.
authors.forename: Assaf
authors.initials: A
authors.lastname: Ben-Meir
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|TCART Fertility Partners, 150 Bloor W, Toronto, ON, M5S 2X9, Canada.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Burstein
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
authors.forename: Aluet
authors.initials: A
authors.lastname: Borrego-Alvarez
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Chong
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Ellen
authors.initials: E
authors.lastname: Wong
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Yavorska
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Taline
authors.initials: T
authors.lastname: Naranian
authors.affiliation: Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA.
authors.forename: Maggie
authors.initials: M
authors.lastname: Chi
authors.affiliation: Department of Biology, McGill University, 3649 Promenade Sir William Osler, Montreal, QC, H3G 0B1, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: TCART Fertility Partners, 150 Bloor W, Toronto, ON, M5S 2X9, Canada.|Department of Obstetrics and Gynecology, University of Toronto, 92 College Street, Toronto, ON, M5G 1L4, Canada.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Bentov
authors.affiliation: LifeQuest Centre for Reproductive Medicine, 655 Bay St, Toronto, ON, M5G 2K4, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Alexis
authors.affiliation: LifeQuest Centre for Reproductive Medicine, 655 Bay St, Toronto, ON, M5G 2K4, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Meriano
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Sung
authors.affiliation: Department of Genetics, University of Pennsylvania, 575 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA, 19104-6145, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Gasser
authors.affiliation: Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA.
authors.forename: Kelle H
authors.initials: KH
authors.lastname: Moley
authors.affiliation: Department of Biology, McGill University, 3649 Promenade Sir William Osler, Montreal, QC, H3G 0B1, Canada.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hekimi
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|TCART Fertility Partners, 150 Bloor W, Toronto, ON, M5S 2X9, Canada.|Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.|Department of Obstetrics and Gynecology, University of Toronto, 92 College Street, Toronto, ON, M5G 1L4, Canada.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Casper
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.|Department of Obstetrics and Gynecology, University of Toronto, 92 College Street, Toronto, ON, M5G 1L4, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jurisicova
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D005260:Female; D005298:Fertility / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014451:Ubiquinone; C024989:coenzyme Q10
keywords: Mitochondria; anti-aging; fecundity; individual; molecular biology of aging; mouse models