Abstract
Specialized cell types of trophoblast cells form the placenta in which each cell type has particular properties of proliferation and invasion. The placenta sustains the growth of the fetus throughout pregnancy and any aberrant trophoblast differentiation or invasion potentially affects the future health of the child and adult. Recently, the field of epigenetics has been applied to understand differentiation of trophoblast lineages and embryonic stem cells (ESC), from fertilization of the oocyte onward. Each trophoblast cell-type has a distinctive epigenetic profile and we will concentrate on the epigenetic mechanism of DNA methyltransferases and TETs that regulate DNA methylation. Environmental factors affecting the mother potentially regulate the DNA methyltransferases in trophoblasts, and so do steroid hormones, cell cycle regulators, such as p53, and cytokines, especially interlukin-1β. There are interesting questions of why trophoblast genomes are globally hypomethylated yet specific genes can be suppressed by hypermethylation (in general, tumor suppressor genes, such as E-cadherin) and how invasive cell-types are liable to have condensed chromatin, as in metastatic cancer cells. Future work will attempt to understand the interactive nature of all epigenetic mechanisms together and their effect on the complex biological system of trophoblast differentiation and invasion in normal as well as pathological conditions.
Highlights
DNMTs and TETs in the regulation of trophoblast invasivenessMember of the DNMT3 family is DNMT3L, which is essential for placental development through establishing maternal gene imprinting (Chédin et al, 2002; Hata et al, 2002; Arima et al, 2006)
EPIGENETIC MECHANISMS ARE INVOLVED IN DEVELOPING A HEALTHY PLACENTA The epigenetic mechanism of DNA methylation partially regulates trophoblast differentiation and invasion into the endometrium of the uterus in order to establish and maintain a healthy placenta for the growing fetus
Over the last decade the study of epigenetics has been applied to many complex biological systems, such as trophoblast differentiation, in order to reach an understanding of the mechanisms and the pathways (Cox et al, 2009, 2011; Choi, 2010; Hemberger, 2010; Senner and Hemberger, 2010; Turner et al, 2012; Arnold et al, 2013)
Summary
Member of the DNMT3 family is DNMT3L, which is essential for placental development through establishing maternal gene imprinting (Chédin et al, 2002; Hata et al, 2002; Arima et al, 2006). TETs are involved in an active DNA demethylation pathway, by converting 5mC to 5-hydroxymethylcytosine (5hmC) (Seisenberger et al, 2013) These epigenetic mechanisms critically regulate the differentiation of cells essential for the development of the placenta and embryo (Table 1) (Ohgane et al, 2002; Rugg-Gunn, 2012). Histone modifications are thought to establish the lineages of inner cell mass and trophectoderm (Nakanishi et al, 2012) and DNA methylation profiles “lock in” and maintain the lineages to create a barrier between them, i.e., to block ESC from becoming trophoblast lineage (Ng et al, 2008; Senner, 2011; Oda et al, 2013). In a microarray study of TET1 knockout mice, 221 genes, mainly developmental, were
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
