Epigenetics and the placenta.
BACKGROUND
The placenta is of utmost importance for intrauterine fetal development and growth. Deregulation of placentation can lead to adverse outcomes for both mother and fetus, e.g. gestational trophoblastic disease (GTD), pre-eclampsia and fetal growth retardation. A significant factor in placental development and function is epigenetic regulation.


METHODS
This review summarizes the current knowledge in the field of epigenetics in relation to placental development and function. Relevant studies were identified by searching PubMed, Medline and reference sections of all relevant studies and reviews.


RESULTS
Epigenetic regulation of the placenta evolves during preimplantation development and further gestation. Epigenetic marks, like DNA methylation, histone modifications and non-coding RNAs, affect gene expression patterns. These expression patterns, including the important parent-of-origin-dependent gene expression resulting from genomic imprinting, play a pivotal role in proper fetal and placental development. Disturbed placental epigenetics has been demonstrated in cases of intrauterine growth retardation and small for gestational age, and also appears to be involved in the pathogenesis of pre-eclampsia and GTD. Several environmental effects have been investigated so far, e.g. ethanol, oxygen tension as well as the effect of several aspects of assisted reproduction technologies on placental epigenetics.


CONCLUSIONS
Studies in both animals and humans have made it increasingly clear that proper epigenetic regulation of both imprinted and non-imprinted genes is important in placental development. Its disturbance, which can be caused by various environmental factors, can lead to abnormal placental development and function with possible consequences for maternal morbidity, fetal development and disease susceptibility in later life.
Department of Obstetrics and Gynaecology, Research Institute Growth & Development (GROW), Center for Reproductive Medicine, Maastricht University Medical Centre, MUMC+, PO Box 5800, 6202 AZ Maastricht, The Netherlands. e.nelissen@mumc.nl
Ewka C M
EC
Nelissen
Aafke P A
AP
van Montfoort
John C M
JC
Dumoulin
Johannes L H
JL
Evers
D019175:DNA Methylation; D004777:Environment; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006657:Histones / Q000378:metabolism; D006801:Humans; D018811:Maternal Exposure; D010920:Placenta / Q000473:pathology; D010922:Placenta Diseases / Q000235:genetics*; D010929:Placentation; D011247:Pregnancy; D022661:RNA, Untranslated / Q000502:physiology
D006657:Histones; D022661:RNA, Untranslated