Mum's in control – even before you're born
BBSRC-funded researchers have uncovered a way by which epigenetic information contained in the egg influences the development of the placenta during pregnancy. The research, performed in mice, indicates that even before conception a mother’s health may influence the health of her fetus.
Epigenetic information is not encoded within the DNA sequence but is critical for determining which genes are on or off. One of the ways this is achieved is via DNA methylation, a biological process where the DNA is chemically tagged to silence genes. DNA methylation marks are laid down in each egg during their development in the ovaries and, after fertilisation, some of these marks are passed onto the fetus and placenta.
In exploring the purpose of this maternal information in fetal development, focus so far has been on a small number of genes termed ‘imprinted genes’. However, there are nearly one thousand other genomic regions where methylation in the egg cell is passed onto the early embryo. The researchers set out to explore the importance of this type of methylation on the development of the placenta and their findings are presented in Developmental Cell.
“We were surprised to find that DNA methylation from the egg played a much larger role in placental development than methylation that was introduced after fertilisation, whereas in the embryo both are important,” explains Miguel Branco, a group leader from Queen Mary University of London who led the work. “Evolution, it seems, has granted mothers the tools to control the growth of their progeny during pregnancy by instructing on placental development.”
By using mice in which methylation of the egg’s DNA had been blocked, the researchers found that DNA methylation occurring during the development of the egg was essential for correct placental development. In particular, the research identified several genes regulated by methylation in the egg that are involved in cell adhesion and migration – both vital properties for cells of the developing placenta in establishing connections with maternal tissues to support embryo development.
“This was an exciting result for us,” said Myriam Hemberger, a group leader at the Babraham Institute. “The phenomenon of gene imprinting explains some of this but our results show that the importance of DNA methylation in early development extends beyond imprinting. Specifically, maternally-inherited DNA methylation marks are important for normal placentation as they specify cellular properties such as adhesiveness and invasive character, as well as determining the correct balance of cell types needed in the placenta.”
The research opens questions regarding the potential influence of maternal health on the fetus long before conception.
“We know that nutrition, environment and ageing affects the DNA methylation pattern in our cells, including in egg cells,” said Wolf Reik, Head of the Epigenetics programme at the Babraham Institute. “One of the questions prompted by this research is whether DNA methylation changes relating to age could contribute to the deterioration of egg quality, subsequently affecting the success of either the embryo or the supporting placenta.”
This work received support from BBSRC, Wellcome Trust, Medical Research Council, the EC Network of Excellence EpiGeneSys, the EC BLUEPRINT project, the Centre for Trophoblast Research, and Canadian Institutes of Health Research.
Notes to editors
Publication reference: Branco et al. (2016) Maternal DNA methylation regulates early trophoblast development. Developmental Cell
About the Babraham Institute
The Babraham Institute, which receives strategic funding (a total of £27.3M in 2014-15) from the Biotechnology and Biological Sciences Research Council (BBSRC), undertakes international quality life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. The Institute’s research provides greater understanding of the biological events that underlie the normal functions of cells and the implication of failure or abnormalities in these processes. Research focuses on signalling and genome regulation, particularly the interplay between the two and how epigenetic signals can influence important physiological adaptations during the lifespan of an organism. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and healthier ageing. www.babraham.ac.uk
About Queen Mary University of London
Queen Mary University of London (QMUL) is one of the UK’s leading universities, and one of the largest institutions in the University of London, with 20,260 students from more than 150 countries.
A member of the Russell Group, we work across the humanities and social sciences, medicine and dentistry, and science and engineering, with inspirational teaching directly informed by our research – in the most recent national assessment of the quality of research, we were placed ninth in the UK (REF 2014).
We also offer something no other university can: a stunning self-contained residential campus in London’s East End. As well as our home at Mile End, we have campuses at Whitechapel, Charterhouse Square and West Smithfield dedicated to the study of medicine, and a base for legal studies at Lincoln’s Inn Fields.
We have a rich history in London with roots in Europe’s first public hospital, St Barts; England’s first medical school, The London; one of the first colleges to provide higher education to women, Westfield College; and the Victorian philanthropic project, the People’s Palace based at Mile End.
QMUL has an annual turnover of £350M, a research income worth £100M, and generates employment and output worth £700M to the UK economy each year. www.qmul.ac.uk
Tags: animal health The Babraham Institute genetics human health press release placenta