Obesity-induced oocyte mitochondrial defects are partially prevented and rescued by supplementation with co-enzyme Q10 in a mouse model

C. E. Boots, A. Boudoures, W. Zhang, A. Drury, K. H. Moley

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Studyquestion: Does supplementation with co-enzymeQ10(CoQ10) improve the oocyte mitochondrial abnormalities associated with obesity in mice? summary answer: In an obese mouse model, CoQ10 improves the mitochondrial function of oocytes. what is known already: Obesity impairs oocyte quality. Oocytes from mice fed a high-fat/high-sugar (HF/HS) diet have abnormalities in mitochondrial distribution and function and in meiotic progression. study design, size, duration: Micewere randomly assigned to a normal, chowdiet or an isocaloricHF/HSdiet for 12 weeks. After 6 weeks on the diet, half of the mice receiving a normal diet and half of the mice receiving a HF/HS diet were randomly assigned to receive CoQ10 supplementation injections for the remaining 6 weeks. participants/materials, setting, methods: Dietary intervention was initiated on C57Bl6 female mice at 4 weeks of age, CoQ10 versus vehicle injections were assigned at 10 weeks, and assays were conducted at 16 weeks of age. Mice were super-ovulated, and oocytes were collected and stained to assess mitochondrial distribution, quantify reactive oxygen species (ROS), assess meiotic spindle formation, and measure metabolites. In vitro fertilization was performed, and blastocyst embryos were transferred into control mice. Oocyte number, fertilization rate, blastulation rate and implantation ratewere compared between the four cohorts. Bivariate statistics were performed appropriately. main results and the role of chance: HF/HS mice weighed significantly more than normal diet mice (29 versus 22 g, P < 0.001). CoQ10 supplementation did not influence weight. Levels of ATP < citrate, and phosphocreatine were lower and ROS levels were higher in HF/HS mice than in controls (P < 0.001). CoQ10 supplementation significantly increased the levels of metabolites and decreased ROS levels in oocytes from normal diet mice but not in oocytes from HF/HS mice. However, CoQ10 completely prevented the mitochondrial distribution abnormalities observed in theHF/HSmice.Overall,CoQ10supplementation significantly increased the percentage of normal spindle and chromosome alignment (92.3 versus 80.2%, P = 0.039). In the sub-analysis by diet, the difference did not reach statistical significance. When undergoing IVF, there were no statistically significant differences in the number of mature oocytes, the fertilization rate, blastocyst formation rates, implantation rates, resorption rates or litter size between HF/HS mice receiving CoQ10 or vehicle injections. limitations, reasons for caution: Experiments were limited to one species and strain of mice. The majority of experiments were performed after ovulation induction, which may not represent natural cycle fertility. wider implications of the findings: Improvement in oocyte mitochondrial distribution and function of normal, chow-fed mice and HF/HS-fed mice demonstrates the importance of CoQ10 and the efficiency of the mitochondrial respiratory chain in oocyte competence. Clinical studies are now needed to evaluate the therapeutic potential of CoQ10 in women's reproductive health. study funding/competing interest(s): C.E.B. received support from the National Research Training Program in Reproductive Medicine sponsored by the National Institute of Health (T32 HD040135-13) and the Scientific Advisory Board of Vivere Health. K.H.M received support fromthe American Diabetes Association and the National Institute of Health (R01 HD083895). There areno conflicts of interest to declare. trial registration number: This study is not a clinical trial.

Original languageEnglish
Pages (from-to)2090-2097
Number of pages8
JournalHuman Reproduction
Volume31
Issue number9
DOIs
StatePublished - Jan 1 2016

Keywords

  • Antioxidant
  • Co-enzyme Q10
  • Electron transport complex
  • Mitochondria
  • Obesity
  • Oocyte quality
  • Spindle and chromosome alignment

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