title: Cell arrest and cell death in mammalian preimplantation development: lessons from the bovine model.
abstract: BACKGROUND
  The causes, modes, biological role and prospective significance of cell death in preimplantation development in humans and other mammals are still poorly understood. Early bovine embryos represent a very attractive experimental model for the investigation of this fundamental and important issue.
  
  
  RESULTS
  To obtain reference data on the temporal and spatial occurrence of cell death in early bovine embryogenesis, three-dimensionally preserved embryos of different ages and stages of development up to hatched blastocysts were examined in toto by confocal laser scanning microscopy. In parallel, transcript abundance profiles for selected apoptosis-related genes were analyzed by real-time reverse transcriptase-polymerase chain reaction. Our study documents that in vitro as well as in vivo, the first four cleavage cycles are prone to a high failure rate including different types of permanent cell cycle arrest and subsequent non-apoptotic blastomere death. In vitro produced and in vivo derived blastocysts showed a significant incidence of cell death in the inner cell mass (ICM), but only in part with morphological features of apoptosis. Importantly, transcripts for CASP3, CASP9, CASP8 and FAS/FASLG were not detectable or found at very low abundances.
  
  
  CONCLUSIONS
  In vitro and in vivo, errors and failures of the first and the next three cleavage divisions frequently cause immediate embryo death or lead to aberrant subsequent development, and are the main source of developmental heterogeneity. A substantial occurrence of cell death in the ICM even in fast developing blastocysts strongly suggests a regular developmentally controlled elimination of cells, while the nature and mechanisms of ICM cell death are unclear. Morphological findings as well as transcript levels measured for important apoptosis-related genes are in conflict with the view that classical caspase-mediated apoptosis is the major cause of cell death in early bovine development.
authors.affiliation: Institute of Anatomy, Histology and Embryology, Department of Veterinary Sciences, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Leidenfrost
authors.forename: Marc
authors.initials: M
authors.lastname: Boelhauve
authors.forename: Myriam
authors.initials: M
authors.lastname: Reichenbach
authors.forename: Tuna
authors.initials: T
authors.lastname: Güngör
authors.forename: Horst-Dieter
authors.initials: HD
authors.lastname: Reichenbach
authors.forename: Fred
authors.initials: F
authors.lastname: Sinowatz
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Felix A
authors.initials: FA
authors.lastname: Habermann
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002452:Cell Count; D002453:Cell Cycle; D016923:Cell Death; D047108:Embryonic Development / Q000235:genetics; D005307:Fertilization in Vitro; D018628:Gene Dosage / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008322:Mammals / Q000196:embryology*; D018613:Microscopy, Confocal; D023421:Models, Animal; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger