title: Delay in oocyte aging in mice by the antioxidant N-acetyl-L-cysteine (NAC).
abstract: BACKGROUND
  Ovarian aging is associated with declining numbers and quality of oocytes and follicles. Oxidative stress by reactive oxygen species (ROS) contributes to somatic aging in general, and also has been implicated in reproductive aging. Telomere shortening is also involved in aging, and telomeres are particularly susceptible to ROS-induced damage. Previously, we have shown that antioxidant N-acetyl-L-cysteine (NAC) effectively rescues oocytes and embryos from ROS-induced telomere shortening and apoptosis in vitro. Using mice as models, we tested the hypothesis that reducing oxidative stress by NAC might prevent or delay ovarian aging in vivo.
  
  
  METHODS
  Initially, young females were treated with NAC in drinking water for 2 months and the quality of fertilized oocytes and early embryo development were evaluated. Next, young mice 1-1½ months old were treated for 1 year with NAC added in drinking water, and their fertility was analyzed starting at 6 months, as indicated by litter size, oocyte number and quality. The ovaries were also examined for telomere activity and length and the expression of selected genes related to aging and DNA damage.
  
  
  RESULTS
  Short-term treatment of mice for 2 months with NAC demonstrated that NAC improved the quality of fertilized oocytes and early embryo development. Mice treated with a long-term low concentration (0.1 mM) of NAC had increased litter sizes at the ages of 7-10 months compared with age-matched controls without NAC treatment. NAC also increased the quality of the oocytes from these older mice. Moreover, the expression of sirtuins was increased, telomerase activity was higher and telomere length was longer in the ovaries of mice treated with NAC compared with those of the control group.
  
  
  CONCLUSIONS
  These data suggest that appropriate treatment with the antioxidant NAC postpones the process of oocyte aging in mice.
authors.affiliation: Department of Cell Biology and Genetics, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
authors.forename: Jinmiao
authors.initials: J
authors.lastname: Liu
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ye
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Junjiu
authors.initials: J
authors.lastname: Huang
authors.forename: Lingling
authors.initials: L
authors.lastname: Wang
authors.forename: Guangzhen
authors.initials: G
authors.lastname: Ji
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Tang
authors.forename: Jay M
authors.initials: JM
authors.lastname: Baltz
authors.forename: David L
authors.initials: DL
authors.lastname: Keefe
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016922:Cellular Senescence / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D008098:Litter Size / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000166:cytology / Q000187:drug effects*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000187:drug effects
chemical_list: D000975:Antioxidants; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D019098:Telomerase; D037761:Sirtuins; D000111:Acetylcysteine