title: Association of abnormal morphology and altered gene expression in human preimplantation embryos.
abstract: OBJECTIVE
  We set out to characterize the expression of nine genes in human preimplantation embryos and determine whether abnormal morphology is associated with altered gene activity.
  
  
  METHODS
  Reverse transcription and real-time polymerase chain reaction were used to quantify the expression of multiple genes in each embryo. The genes studied have various important cellular roles (e.g., cell cycle regulation, DNA repair, and apoptosis).
  
  
  METHODS
  Research laboratory working closely with a clinical IVF practice.
  
  
  METHODS
  Over 50 embryos were donated by infertile patients (various etiologies). Among these, all major stages of preimplantation development and a variety of common morphologic abnormalities were represented.
  
  
  METHODS
  None.
  
  
  METHODS
  Quantification of mRNA transcripts.
  
  
  RESULTS
  We detected an association between certain forms of abnormal morphology and disturbances of gene activity. Cellular fragmentation was associated with altered expression of several genes, including TP53, suggesting that fragmenting blastomeres are suffering stress of a type monitored by p53, possibly as a consequence of suboptimal culture conditions.
  
  
  CONCLUSIONS
  Appropriate gene expression is vital for the regulation of metabolic pathways and key developmental events. Our data indicates a possible causal relationship between changes in gene expression and the formation of clinically relevant abnormal embryo morphologies. We hypothesize that embryos with expression profiles characteristic of good morphology and appropriate for their developmental stage have the greatest potential for implantation. If confirmed, this could lead to a new generation of preimplantation genetic diagnosis (PGD) tests for assessing embryo viability and predicting implantation potential.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University Medical School, New Haven, Connecticut 06520, USA. dagan.wells@yale.edu
authors.forename: Dagan
authors.initials: D
authors.lastname: Wells
authors.forename: Mercedes G
authors.initials: MG
authors.lastname: Bermúdez
authors.forename: Nury
authors.initials: N
authors.lastname: Steuerwald
authors.forename: Henry E
authors.initials: HE
authors.lastname: Malter
authors.forename: Alan R
authors.initials: AR
authors.lastname: Thornhill
authors.forename: Jacques
authors.initials: J
authors.lastname: Cohen
mesh_terms: D001755:Blastocyst / Q000502:physiology*; D016000:Cluster Analysis; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D016133:Polymerase Chain Reaction / Q000379:methods