Epigenetic regulation of epithelial to mesenchymal transition: a trophoblast perspective.

Epigenetic changes alter the expression of genes at both pre- and post-transcriptional levels without changing their DNA sequence. Accumulating evidence suggests that such changes can modify cellular behavior and characteristics required during development and in response to various extracellular stimuli. Trophoblast cells develop from the outermost trophectoderm layer of the blastocyst and undergo many phenotypic changes as the placenta develops. One such phenotypic change is differentiation of the epithelial natured cytotrophoblasts into the mesenchymal natured extravillous trophoblasts. The extravillous trophoblasts are primarily responsible for invading into the maternal decidua and thus establishing connection with the maternal spiral arteries. Any dysregulation of this process can have adverse effects on the pregnancy outcome. Hence, tight regulation of this epithelial-mesenchymal transition (EMT) is critical for successful pregnancy. This review summarizes the recent research on the epigenetic regulation of the EMT occurring in the trophoblast cells during placental development. The functional significance of chemical modifications of DNA and histone, which regulate transcription, as well as non-coding RNAs, which control gene expression post-transcriptionally, is discussed in relation to trophoblast biology.