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In humans, successful pregnancy depends on a cascade of dynamic events during early embryonic development. Unfortunately, molecular data on these critical events is scarce. To improve our understanding of the molecular mechanisms that govern the specification/development of the trophoblast cell lineage, the transcriptome of human trophectoderm (TE) cells from day 5 blastocysts was compared to that of single day 3 embryos from our  in vitro  fertilization program by using Human Genome U133 Plus 2.0 microarrays. Some of the microarray data were validated by quantitative RT-PCR. The TE molecular signature included 2,196 transcripts, among which were genes already known to be TE-specific ( GATA2 ,  GATA3  and  GCM1)  but also genes involved in trophoblast invasion ( MUC15) , chromatin remodeling (specifically the DNA methyltransferase  DNMT3L)  and steroid metabolism ( HSD3B1 ,  HSD17B1  and  FDX1).  In day 3 human embryos 1,714 transcripts were specifically up-regulated. Besides stemness genes such as  NANOG  and  DPPA2 , this signature included genes belonging to the  NLR  family ( NALP4 ,  5 ,  9 ,  11  and  13 ), Ret finger protein-like family ( RFPL1, 2  and  3 ), Melanoma Antigen family ( MAGEA1 ,  2 ,  3 ,  5 ,  6  and  12 ) and previously unreported transcripts, such as  MBD3L2  and  ZSCAN4 . This study provides a comprehensive outlook of the genes that are expressed during the initial embryo-trophectoderm transition in humans. Further understanding of the biological functions of the key genes involved in steroidogenesis and epigenetic regulation of transcription that are up-regulated in TE cells may clarify their contribution to TE specification and might also provide new biomarkers for the selection of viable and competent blastocysts.

Transcriptome Analysis during Human Trophectoderm Specification Suggests New Roles of Metabolic and Epigenetic Genes