title: Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity.
abstract: Mitochondria affect numerous aspects of mammalian reproduction. We investigated whether the decrease in oocyte quality associated with aging is related to altered mitochondria. Oocytes from old (12 months) and young (9 weeks) C57BL/6J mice were compared in relation to: mitochondria morphology and dynamics (mitochondria density, coverage, size and shape) throughout folliculogenesis; levels of mitochondrial DNA (mtDNA); mitochondrial stress reflected in the expression of mitochondrial unfolded protein response (mt-UPR) genes; and levels of reactive oxygen species (ROS) under baseline conditions and following H2O2treatment. In old mice, mitochondria of primary follicle-enclosed oocytes were smaller, with lower mitochondria coverage (total mitochondria μm2/μm2cytosol area) (p<0.05). Other follicular stages showed a similar trend, but the changes were not significant. Mature oocytes (Metaphase II-MII) from old mice had significantly less mtDNA (p<0.01), and elevated mt-UPR gene Hspd1 expression (p<0.05), compared with those from young mice. ROS levels in aged MII oocytes were also higher following pretreatment with H2O2(p<0.05). Aging is associated with altered mitochondrial morphological parameters and decreased mtDNA levels in oocytes, as well as an increase in ROS under stressful conditions and elevated expression of mitochondrial stress response gene Hspd1. Delineation of the mechanisms underlying mitochondrial changes associated with ageing may help in the development of diagnostic and therapeutic tools in reproductive medicine.
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06520, USA.
authors: Elnur
authors: E
authors: Babayev
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06520, USA; Department of Obstetrics, Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Tianren
authors: T
authors: Wang
authors: Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
authors: Klara
authors: K
authors: Szigeti-Buck
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06520, USA.
authors: Katie
authors: K
authors: Lowther
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06520, USA.
authors: Hugh S
authors: HS
authors: Taylor
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06520, USA; Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
authors: Tamas
authors: T
authors: Horvath
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: emre.seli@yale.edu.
authors: Emre
authors: E
authors: Seli
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000235:genetics*; D009865:Oocytes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012098:Reproduction
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide
keywords: Aging; Mitochondria; Oocyte; Reproduction