Epigenetic features of the mouse trophoblast

Trophoblast cells are required for the growth and survival of the fetus during pregnancy, and failure to maintain appropriate trophoblast regulation is associated with placental insufficiencies and intrauterine growth restriction. Development of the trophoblast lineage is mediated by interactions between genetic and epigenetic factors. This review will focus on new insights that have been gained from analysis of mouse models into the epigenetic mechanisms that are required for the early establishment of the trophoblast lineage and for the development of specialized cell types of the fetal placenta. In particular, the importance of DNA methylation, 5-hydroxymethylcytosine and histone modifications in orchestrating trophoblast gene expression and functional outcome will be discussed. These insights are beginning to be extended towards human studies and initial results suggest that the causes and consequences of a variety of placental pathologies are related to epigenetic processes. Furthermore, the epigenetic landscape that regulates trophoblast cells seems to be particularly vulnerable to perturbation during development. This has major implications for diet and other environmental factors during pregnancy.The placenta is required for the growth and survival of the fetus during pregnancy. Placental insufficiencies, including pre-eclampsia and intrauterine growth restriction, occur in ∼10% of pregnancies and are associated with serious complications for mother and baby. Better understanding of how the placenta is formed is critical for the development of early diagnoses and therapies for treatment. Studies of animal models have revealed several critical pathways that are required for the proper development and function of the placenta. In particular, epigenetic processes, which determine how genes are switched on and off, are necessary for the early establishment of the placental lineage and also for the development of specialized cell types within the mature placenta. These crucial and recent insights form the basis for this review. Importantly, much of our understanding gleaned from animal models are now beginning to be extended towards human studies. Initial results suggest that the causes and consequences of a variety of placental pathologies are related to epigenetic pathways. As epigenetic processes can be susceptible to alterations by environmental factors, these studies have major implications for diet and other external influences during pregnancy.