title: Long-term effects of repeated superovulation on ovarian structure and function in rhesus monkeys.
abstract: OBJECTIVE
  To assess the long-term effects of repeated controlled ovarian hyperstimulation (COH) on ovarian structure and function.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Adult female rhesus macaques.
  
  
  METHODS
  A repeated COH rhesus macaque model (superovulation group) with spontaneously ovulating macaques used as controls (normal group) and samples of serum and ovarian tissue collected over a 5-year period.
  
  
  METHODS
  Steroid hormone levels, and structural, functional, and protein changes in ovaries.
  
  
  RESULTS
  The follicular histology, proportion of follicles at each developmental stage, and expression levels of oocyte-specific genes showed no statistically significant differences between the two groups. However, the superovulation group exhibited mitochondrial abnormalities in the granulosa cells and a low expression of genes involved in steroid hormone synthesis compared with the normal group. A comparison of protein expression in the ovaries of both groups using tandem mass tag labeling with mass spectrometry revealed that most of the differentially-expressed proteins were down-regulated in the superovulation group. These proteins were mainly localized in the mitochondria and cytosol, and changes in protein levels in the superovulation group mainly inhibited cell proliferation and differentiation but promoted apoptosis.
  
  
  CONCLUSIONS
  Our study indicates that repeated COH could change the expression of many proteins in the ovaries even after several years, potentially affecting the development and function of ovarian cells.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yueshuai
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Zuomin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China. Electronic address: njzhuhui@njmu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D008137:Longitudinal Studies; D008253:Macaca mulatta; D009865:Oocytes / Q000166:cytology*; D010053:Ovary / Q000166:cytology* / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D013480:Superovulation / Q000097:blood / Q000502:physiology*
chemical_list: D012739:Gonadal Steroid Hormones; D020543:Proteome
keywords: Controlled ovarian stimulation; ovarian follicular structure; proteomics; rhesus macaques; superovulation