title: Genome-wide identification of aberrantly methylated promoters in ovarian tissue of prenatally androgenized rats.
abstract: OBJECTIVE
  To identify aberrantly methylated candidate genes that are involved in the development of polycystic ovary syndrome (PCOS).
  
  
  METHODS
  Animal model.
  
  
  METHODS
  University-affiliated laboratory.
  
  
  METHODS
  Sprague-Dawley rats.
  
  
  METHODS
  The prenatally androgenized (PNA) rat model was established. Pregnant rats were treated with daily SC injections of T propionate during late gestation, and their female offspring were studied as adults.
  
  
  METHODS
  Serum glucose and hormone levels, ovary morphology and cell apoptosis, genome-wide CpG methylation, and expression of caspase-3 protein were measured.
  
  
  RESULTS
  In the PNA group, the levels of serum glucose, 17-hydroxyprogesterone, and T were significantly higher when compared with the control group. Ovarian morphology showed increased atretic follicles and cystic follicles. Using the MeDIP-chip approach, we identified 528 genes that were hypermethylated in PNA ovaries. Gene ontology analyses revealed that these genes are involved in a variety of reproductive development and biological processes. The methylation enrichments of Bcl2l1 and Scr5a1 observed in the PNA group by MeDIP-quantitative polymerase chain reaction assay were significantly higher than those obtained from the control group. Furthermore, the mRNA level of the Bcl2l1 gene was significantly decreased in the PNA group. The percentage of caspase-3-positive cells in the PNA group was obviously higher compared with the control group, by terminal deoxynucleotidyl transferase dUTP nick end labeling detection as well.
  
  
  CONCLUSIONS
  DNA methylation alteration may be an important factor affecting the genes involved in the pathophysiological processes that result in the phenotype of PCOS.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Duojia
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cong
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China. Electronic address: xiaokewu2002@vip.sina.com.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D010053:Ovary / Q000187:drug effects / Q000503:physiopathology*; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000235:genetics*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020543:Proteome / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043343:Testosterone Propionate; D014770:Virilism / Q000139:chemically induced / Q000235:genetics*
chemical_list: D020543:Proteome; D043343:Testosterone Propionate
keywords: DNA methylation; Polycystic ovary syndrome; epigenetics; prenatal androgenization