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

<div><p>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 <em>in vitro</em> 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 (<em>GATA2</em>, <em>GATA3</em> and <em>GCM1)</em> but also genes involved in trophoblast invasion (<em>MUC15)</em>, chromatin remodeling (specifically the DNA methyltransferase <em>DNMT3L)</em> and steroid metabolism (<em>HSD3B1</em>, <em>HSD17B1</em> and <em>FDX1).</em> In day 3 human embryos 1,714 transcripts were specifically up-regulated. Besides stemness genes such as <em>NANOG</em> and <em>DPPA2</em>, this signature included genes belonging to the <em>NLR</em> family (<em>NALP4</em>, <em>5</em>, <em>9</em>, <em>11</em> and <em>13</em>), Ret finger protein-like family (<em>RFPL1, 2</em> and <em>3</em>), Melanoma Antigen family (<em>MAGEA1</em>, <em>2</em>, <em>3</em>, <em>5</em>, <em>6</em> and <em>12</em>) and previously unreported transcripts, such as <em>MBD3L2</em> and <em>ZSCAN4</em>. 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.</p>