title: Resveratrol protects against age-associated infertility in mice.
abstract: OBJECTIVE
  Does resveratrol counteract age-associated infertility in a mouse model of reproductive aging?
  
  
  CONCLUSIONS
  Long-term-oral administration of resveratrol protects against the reduction of fertility with reproductive aging in mice.
  
  
  BACKGROUND
  Loss of oocytes and follicles and reduced oocyte quality contribute to age-associated ovarian aging and infertility. Accumulation of free radicals with age leads to DNA mutations, protein damage, telomere shortening, apoptosis and accelerated ovarian aging. Increasing evidence shows that resveratrol, enriched in certain foods, for example red grapes and wine, has anti-tumor and anti-aging effects on somatic tissues by influencing various signaling pathways, including anti-oxidation, as well as activating Sirt1 and telomerase. We investigated the potential of resveratrol to stave off ovarian aging in the inbred C57/BL6 mouse model.
  
  
  METHODS
  Young C57/BL6 females (aged 2-3 months) were fed with resveratrol added to drinking water at 30 mg/l (providing ∼7.0 mg/kg/day) for 6 or 12 months, and the fertility and ovarian functions were compared among mice treated with or without resveratrol, and young mice served as reproductive controls. Experiments were repeated three times, with an average of 25 females randomly allocated to each treatment group for each repeat.
  
  
  METHODS
  Reproductive performance of female mice was determined by litter size, ovarian follicles and oocyte quantity and quality, and compared with age-matched controls. The impact of resveratrol on telomeres and telomerase activity, and expression of genes associated with cell senescence also was evaluated.
  
  
  RESULTS
  Young mice fed with resveratrol for 12 months retained the capacity to reproduce, while age-matched controls produced no pups. Consistently, mice fed with resveratrol for 12 months exhibited a larger follicle pool than controls (P < 0.05). Furthermore, telomerase activity, telomere length and age-related gene expression in ovaries of mice fed with resveratrol resembled those of young mice, but differed (P < 0.05) from those of age-matched old mice. Resveratrol improved (P < 0.05) the number and quality of oocytes, as evidenced by spindle morphology and chromosome alignment. Also, resveratrol affected embryo development in vitro in a dose-dependent manner.
  
  
  CONCLUSIONS
  The doses of resveratrol and the experimental conditions used by different research groups have varied considerably, and the dosage influences both the effectiveness and toxicity of resveratrol. Fine-tuning the dosage of resveratrol likely will optimize its anti-aging effects on ovarian function.
  
  
  CONCLUSIONS
  Our data provide a proof of principle of the fertility-sparing effect of resveratrol in female mice. Although depletion of the ovarian reserve of high-quality oocytes also contributes to increased infertility with reproductive aging in women, the data obtained using a mouse model may not extrapolate directly to human reproduction, and more extensive research is needed if any clinic trials are to be attempted.
  
  
  BACKGROUND
  This work was supported by MOST of China National Basic Research Program (grant number: 2010CB94500 and 2012CB911200). The authors have no competing interests to declare.
authors.affiliation: Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Yin
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ye
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: David L
authors.initials: DL
authors.lastname: Keefe
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004477:Ectogenesis / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007247:Infertility, Female / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009866:Oogenesis / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D016649:Primary Ovarian Insufficiency / Q000503:physiopathology / Q000517:prevention & control; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D019098:Telomerase / Q000378:metabolism; D059506:Telomere Shortening / Q000187:drug effects
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D019098:Telomerase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D016283:Proto-Oncogene Proteins p21(ras); D000077185:Resveratrol