title: Supraphysiological estrogen levels adversely impact proliferation and histone modification in human embryonic stem cells: possible implications for controlled ovarian hyperstimulation assisted pregnancy.
abstract: OBJECTIVE
  Controlled ovarian hyperstimulation (COH) results in supraphysiologic levels of maternal serum estradiol (E(2)) during the luteal phase, thus promoting oocyte production at unknown risk to the subsequently developing embryo. Human embryonic stem cells (hESCs) have been identified as a model system to assess the impact of COH on early embryonic development, specifically 17β-estradiol mediated effects on proliferation, gene expression, and histone modification.
  
  
  METHODS
  Cell proliferation and associated factors, such as HDAC1, as well as histone modification patterns were evaluated in ERα and β expressing hESCs after exposure to 17β-estradiol (1×10(-10) M to 1×10(-7) M), as well as in an untreated control.
  
  
  RESULTS
  Resultant data revealed that while physiologically relevant E(2) levels (1×10(-9)M E(2)) induced cell cycle progression from G1 to the proliferation phase, supraphysiologic levels akin to those observed after COH (1×10(-7) M E(2)) adversely affected hESCs proliferation via down regulation of HDAC1. Modification of H3K9me2, PhH3S10, H4K5ac, and H2A.Z histone patterns were also dependent on 17β-estradiol concentration.
  
  
  CONCLUSIONS
  While physiologic levels of 17β-estradiol induced cell proliferation, possibly via HDAC1 involvement in histone modification, cell proliferation in hESCs was suppressed at supraphysiologic levels.
authors.affiliation: Center for Reproductive Medicine, First Affiliated Hospital, Sun Yat-sen University, People's Republic of China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Wang
authors.forename: Canquan
authors.initials: C
authors.lastname: Zhou
authors.forename: Weijia
authors.initials: W
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.forename: Guanglun
authors.initials: G
authors.lastname: Zhuang
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009994:Osmolar Concentration; D010062:Ovulation Induction / Q000379:methods; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013480:Superovulation / Q000187:drug effects*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D006657:Histones; D012333:RNA, Messenger; D004958:Estradiol; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1