title: Apoptotic effects of high estradiol concentrations on endometrial glandular cells.
abstract: BACKGROUND
  High serum estradiol (E2) concentrations result in adverse reproductive outcome in in vitro fertilization cycles, and the detrimental effects are probably due to impaired endometrial receptivity.
  
  
  OBJECTIVE
  Endometrial glandular cells (EGCs) are the cells that embryos first interact with during implantation. Our objective is to examine the in vitro EGC alterations after high E2 treatment.
  
  
  METHODS
  This was a prospective study.
  
  
  METHODS
  The study was conducted at a tertiary university hospital.
  
  
  METHODS
  Six women in the follicular phase participated in the study.
  
  
  METHODS
  EGCs were purified from human endometrium and cultured with different concentrations (0, 10(-9), 10(-8), 10(-7), 10(-5), 10(-4) M) of E2.
  
  
  METHODS
  EGC apoptosis and its underlying mechanism were measured.
  
  
  RESULTS
  In vitro BeWo spheroid-EGC implantation assay demonstrated that the stimulation with 10(-5) and 10(-4) M E2 for 2 days decreased embryo implantation potentials. Presence of apoptotic bodies and DNA fragmentation and an increased percentage of sub-G1 phase were found in EGCs treated with high E2 concentrations. The high E2-treated EGCs could be rescued from apoptosis after the addition of estrogen receptor antagonist ICI 182 780. Western blot revealed increased inhibitory-κB (IκB)-α expression and decreased nuclear factor-κB (NF-κB) expression in high E2-treated EGCs, and NF-κB binding site-driven luciferase activity was decreased as well. When EGCs were pretreated with IκB-α small interfering RNA, high E2-induced B cell lymphoma 2 (Bcl-2) down-regulation did not occur and EGCs apoptosis was reduced. Bcl-2 overexpression also rescued high E2-induced EGCs from apoptosis.
  
  
  CONCLUSIONS
  High E2 concentrations induced EGCs apoptosis through enhancing IκB-α expression, which in turn suppressed NF-κB expression. The decreased nuclear NF-κB subsequently inhibited Bcl-2 expression and accordingly enhanced EGC apoptosis.
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Shee-Uan
authors.initials: SU
authors.lastname: Chen
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chou
authors.forename: Mei-Jou
authors.initials: MJ
authors.lastname: Chen
authors.forename: Tzu-Hsin
authors.initials: TH
authors.lastname: Chen
authors.forename: Yu-Shih
authors.initials: YS
authors.lastname: Yang
authors.forename: Jehn-Hsiahn
authors.initials: JH
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005498:Follicular Phase / Q000187:drug effects; D000077267:Fulvestrant; D006801:Humans; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000077267:Fulvestrant; D004958:Estradiol