OBJECTIVE: To investigate the role of the blastocyst in implantation failure. This study examined trophectoderm (TE) gene expression relative to pregnancy outcome. DESIGN: Retrospective experimental study. SETTING: Nonprofit research foundation. ANIMAL(S): Six-week-old BDF1 female mice. INTERVENTION(S): Hatching blastocysts underwent trophectoderm biopsy before single blastocyst transfer (one per uterine horn). MAIN OUTCOME MEASURES: Blinded gene expression analysis was performed on biopsied TE cells by quantitative real-time polymerase chain reaction (Q RT-PCR). Healthy placenta and absorption sites were biopsied on day 16 of fetal development for comprehensive transcriptome analysis with validation by Q RT-PCR. RESULT(S): Compared with blastocysts that resulted in healthy fetal development, blastocysts that failed to implant (negative) showed decreased B3gnt5 and Eomes gene expression, while blastocysts that resulted in spontaneous pregnancy loss (absorption) displayed decreased Wnt3a and Eomes gene expression. Comprehensive transcriptome analysis of biopsied absorption sites and healthy placenta revealed distinct gene expression signatures, with 5,918 significantly altered transcripts (greater than twofold). The predominantly altered pathways associated with spontaneous pregnancy loss were the complement and coagulation cascades. CONCLUSION(S): This study revealed for the first time that individual blastocyst gene expression profiles correlate with outcome, including successful implantation and pregnancy loss.
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