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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. DESIGN: 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). SETTING: Research laboratory working closely with a clinical IVF practice. PATIENT(S): 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. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantification of mRNA transcripts. RESULT(S): 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. CONCLUSION(S): 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.

Original publication

DOI

10.1016/j.fertnstert.2005.01.143

Type

Journal article

Journal

Fertil Steril

Publication Date

08/2005

Volume

84

Pages

343 - 355

Keywords

Blastocyst, Cluster Analysis, Embryo, Mammalian, Embryonic Development, Gene Expression Regulation, Developmental, Humans, Polymerase Chain Reaction