title: Obesity accelerates ovarian follicle development and follicle loss in rats.
abstract: OBJECTIVE
  Studies have shown that excess body fat negatively affects reproductive functions in females. However, whether obesity affects the ovarian follicle development and ovarian lifespan and the underlying mechanism has not been well elucidated. The aim of the present study was to investigate the association between obesity and ovarian follicle development.
  
  
  METHODS
  Adult female Sprague-Dawley rats (n = 36) were randomly divided into three groups: the normal control (NC) group, the caloric restriction (CR) group (fed 70% food of the NC group) and the high-fat diet (HF) group. They were maintained on these regimens for 18 weeks.
  
  
  RESULTS
  The body weight, ovary weight and visceral fat in the HF group were significantly higher than those in the NC group and the CR group at the end of treatment. Histological analysis showed that the HF rats had significantly less number and percentage of primordial follicles, but greater number and percentage of developing and atretic follicles than the NC rats and CR rats. Western blot analysis demonstrated that the level of mTORC1 and p-S6K1 proteins significantly increased in the ovaries of HF rats, whereas that of SIRT1, SIRT6, FOXO3a and NRF-1 decreased compared to the NC rats. In contrast, the expression of mTORC1 and p-S6K1 dramatically declined, while that of SIRT1, SIRT6, FOXO3a and NRF1 increased in the ovaries of CR rats.
  
  
  CONCLUSIONS
  Our study suggests that the HF diet induced obesity may accelerate the ovarian follicle development and rate of follicle loss through activating mTOR and suppressing SIRT1 signaling, thus leading to POF, and that CR may inhibit the activation of primordial follicles, follicular development and loss, thus extending the ovarian lifespan through suppressing mTOR and activating SIRT1 signaling.
authors.affiliation: Laboratory of Cell Senescence, Shantou University Medical College, Xinling Road 22, Shantou 515041, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Luo
authors.forename: Jin-Jie
authors.initials: JJ
authors.lastname: Xu
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Xu
authors.forename: Xing-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zhou
authors.forename: Wei-Juan
authors.initials: WJ
authors.lastname: Liu
authors.forename: Yu-Cai
authors.initials: YC
authors.lastname: Fu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D059305:Diet, High-Fat; D005260:Female; D007150:Immunohistochemistry; D050152:Intra-Abdominal Fat / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000473:pathology*; D006080:Ovarian Follicle / Q000254:growth & development / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: 3, 3′-diaminobenzidine; 4E-BP1; AB; CLC; CO; CR; DAB; FOXO3a; GC; GE; GTP; H&E; HF; NC; NRF-1; ON; Obesity; Ovarian development; Ovarian lifespan; PAGE; PBS; PG; POF; Rat; S.E.M; S6K1; SDS; SIRT; SPSS; Statistical Package for the Social Sciences; TC; TSC; apoptotic body; calorie restriction; corpora lutea cell; cumulus oophorus; eukaryotic initiation factor 4E binding protein 1; forkhead box group O; granular cell; gross energy; guanosine triphosphate; hematoxylin and eosin; high fat; mTOR; mTORC; mammalian target of rapamycin; mammalian target of rapamycin complex; normal control; nuclear respiratory factor 1; oocyte nucleus; p70 ribosomal protein S6 kinases; phosphate buffer solution; polyacryl amide gel electrophoresis; pre-granular cell; premature ovarian failure; silent information regulator; sodium dodecyl sulfate; standard error of mean; the tuberous sclerosis complex; thecal cell