title: Unfolded protein response prevents blastocyst formation during preimplantation embryo development in vitro.
abstract: OBJECTIVE
  To study the effect of increased endoplasmic reticulum (ER) stress as a major nongenomic mechanism for arrested blastocyst development.
  
  
  METHODS
  Cell and animal study.
  
  
  METHODS
  The Ohio State University and Yale University.
  
  
  METHODS
  Mice.
  
  
  METHODS
  Pregnant mare serum gonadotropin and hCG were administered IP; two cell embryos were collected 48 hours after hCG administration.
  
  
  METHODS
  Blastocyst development rate.
  
  
  RESULTS
  No morphological difference was detected in control versus tunicamycin- (TM) treated embryos until the blastocyst stage. On day 4 of embryonic development, TM treatment reduced blastocyst formation from 79% to 4% and induced nuclear fragmentation. TM treatment caused 2-fold and 2.6-fold increase in binding immunoglobulin protein and spliced-X-box binding protein 1 mRNA expression, respectively. By comparison, the tauroursodeoxycholic acid + TM combination reversed the effect of TM alone on blastocyst formation to near control levels.
  
  
  CONCLUSIONS
  These results indicate that increased ER stress during in vitro embryo development triggers an unfolded protein response (UPR) that negatively affects blastocyst formation and suggests that activation of UPR signaling may account for low rates of blastocyst development.
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, Ohio; Department of Histology and Embryology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Basar
authors.affiliation: Department of Histology and Embryology, Dokuz Eylul Medical Faculty, Izmir, Turkey; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Idil
authors.initials: I
authors.lastname: Bozkurt
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, Ohio; Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Guzeloglu-Kayisli
authors.affiliation: Department of Histology and Embryology, Akdeniz University Medical Faculty, Antalya, Turkey.
authors.forename: Berna
authors.initials: B
authors.lastname: Sozen
authors.affiliation: Department of Histology and Embryology, Dokuz Eylul Medical Faculty, Izmir, Turkey.
authors.forename: Isil
authors.initials: I
authors.lastname: Tekmen
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, Ohio; Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida.
authors.forename: Frederick
authors.initials: F
authors.lastname: Schatz
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Aydin
authors.initials: A
authors.lastname: Arici
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, Ohio; Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, Ohio; Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida. Electronic address: uakayisli@health.usf.edu.
authors.forename: Umit A
authors.initials: UA
authors.lastname: Kayisli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001755:Blastocyst / Q000502:physiology*; D046149:Embryo Culture Techniques; D047108:Embryonic Development / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D051379:Mice; D056811:Unfolded Protein Response
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006064:Gonadotropins, Equine; D006360:Heat-Shock Proteins
keywords: Preimplantation embryo development; apoptosis; developmental arrest; endoplasmic reticulum stress; unfolded protein response