skip to content

Department of Physiology, Development and Neuroscience


Epigenetic changes accrued in the genome throughout one’s lifetime can contribute to an increased risk for disease. These changes may occur through exposure to environmental stressors (e.g., toxins, nutrient deficiency, etc.) that alter epigenetic factors, such as patterns of DNA methylation, ultimately causing gene misexpression. Exposure to these environmental factors in utero may alter epigenetic programming, such that the nine months before you are born may have a profound impact on your health later in life. Mounting evidence also indicates that maternal, paternal or even grandparental exposure may contribute to congenital malformations and/or metabolic and cardiovascular diseases in children and grandchildren. This non-conventional inheritance occurs via epigenetic rather than genetic inheritance, and implicates the germline. Very little is understood regarding transgenerational mechanisms of inheritance. Our aim is to explore how developmental abnormalities and disease risk is epigenetically transmitted between generations. Further understanding this mechanism will drastically impact human health.

Transgenerational epigenetic effects of folate metabolism

My group currently explores the mechanisms behind the transgenerational epigenetic effects of folate metabolism during fetal and placental development. Folate is a vitamin important for the one-carbon metabolism and methylation of cell components (e.g., DNA). To study this, we use a genetic mouse model with a mutation in a key gene involved in folate metabolism (Mtrrgt) that disrupts folate metabolism and results in similar metabolic effects as human folate deficiency. We recently showed using highly controlled genetic pedigrees that when either maternal grandparent carried the Mtrrgt mutant allele, it was sufficient to cause developmental abnormalities and epigenetic instability in their grandprogeny at midgestation (Padmanabhan et al, 2013 Cell). This occurred even when the mother and the grandprogeny are genetically wildtype for the Mtrr mutation. Some of the abnormalities (e.g., neural tube, heart and placental defects) persisted after embryo transfer experiments and for up to 5 generations, implicating epigenetic inheritance as a mechanism.

Our research goal is to use the Mtrr mouse model to understand the mechanism behind the transgenerational effects of folate metabolism on development by breaking it down into the specific properties of each generation (i.e., grandparental, maternal and placental/embryonic effects) using epigenetic, molecular and embryo manipulation techniques. Ultimately, this will help us explain the role of folate metabolism during development, which has eluded researchers for decades. As well, it will give us clues as to how transgenerational inheritance of disease and phenotypes is achieved.


Current lab members

Dr Claire Senner (Next Generation Fellow, Centre for Trophoblast Research)

Charlotte Handford (PhD student [co-supervised by Magdalena Zernicka-Goetz], CTR studentship)

Amy Wilkinson (PDN Part II student)

George Nishimura (PDN Part II student)


Main collaborators

Prof Anne Ferguson-Smith (Dept Genetics, University of Cambridge)

Prof Graham Burton and Dr Hong Wa Yung (Dept PDN, University of Cambridge)

Dr Andrew Murray (Dept PDN, University of Cambridge)

Dr Russell Hamilton (CTR, University of Cambridge)

Prof Magdalena Zernicka-Goetz (Dept PDN, University of Cambridge; CALTECH, USA)

Dr Eric Miska and Dr Katharina Gapp (Gurdon Institute, Cambridge)


Editorial Board Member

Associate editor, Reproduction

Editorial review board member, Environmental Epigenetics



Key publications: 

Blake GET, Zhao X, Yung HW, Burton GJ, Ferguson-Smith AC, Hamiliton RS, Watson ED (2020) Defective folate metabolism causes germline epigenetic instability and distinguishes HIRA as a phenotype inheritance biomarker. bioRxiv preprint

Sowton A, Padmanabhan N, Tunster SJ, McNally B, Murgia A, Yusuf A, Griffin JL, Murray AJ, Watson ED, (2020) Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice. Molecular Genetics and Metabolism Reports 23: 100580 

Tunster SJ, Watson ED, Fowden AL, Burton GJ. Placenta glycogen stores and fetal growth: evidence from genetic mouse models. (2020) Reproduction 159(6): R213-R235

Menelaou K, Prater M, Tunster SJ, Blake GET, Geary Joo C, Cross JC, Hamilton RS, Watson ED, (2020), Blastocyst transfer in mice alters the placenta transcriptome and growth, Reproduction 156(2): 115-132

Blake GET, Hall J, Petkovic GE, Watson ED, (2019), Analysis of spermatogenesis and fertility in adult mice with a hypomorphic mutation in the Mtrr gene, Reproduction, Fertility and Development 31(11): 1730-1740 

Padmanabhan N, Menelaou K, Gao J, Anderson A, Blake GET, Li T, Daw BN, Watson ED, (2018), Abnormal folate metabolism causes age-, sex-, and parent-of-origin specific haematological defects in mice, The Journal of Physiology, 596(18): 4341-60

Padmanabhan N, Rakoczy J, Kondratowicz M, Menelaou K, Blake GET, Watson ED, (2017), Multigenerational analysis of sex-specific phenotypic differences at midgestation caused by abnormal folate metabolismEnvironmental Epigenetics, 3(4): 1-17

Rakoczy J, Padmanabhan N, Krzak AM, Kieckbusch J, Cindrova-Davies T, Watson ED, (2017), Dynamic expression of TET1, TET2, and TET3 dioxygenases in mouse and human placentas throughout gestationPlacenta, 59: 46-56

Blake GET, Watson ED, (2016), Unravelling the complex mechanisms of transgenerational epigenetic inheritance, Current Opinion in Chemical Biology, 33: 101-7

Watson ED, Rakoczy J, (2016), Fat eggs shape offspring health, Nature Genetics, 48: 478-9

Watson ED, (2016), Transferring fragments of paternal metabolism to the offspring, Cell Metabolism, 23(3): 401-2

Padmanabhan N, Jia D, Geary-Joo C, Wu X, Ferguson-Smith AC, Fung E, Bieda M, Snyder FF, Gravel RA, Cross JC, Watson ED, (2013), Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development, Cell, 155(1): 81-93

Teaching and Supervisions


Part IB Human Reproduction

Part IB Veterinary Reproductive Biology

Part IB NST Physiology

PDN Part II, P2 module


Lecturer in Reproductive Biology
Lister Research Prize Fellow
Dr Erica D Watson

Contact Details

+44 (0) 1223 333858, Lab: +44 (0) 1223 746744
Email address: 

Plain English

We are trying to figure out how our environment affects the development of our grandchildren. For example, we know that a poor diet can alter how our genes are expressed and increase our risk for disease. Epigenetics is a layer of instructions that tells a cell how to control gene expression. This involves changes in chemicals called methyl groups that attach to DNA or RNA and flip their 'on/off' switch. We are interested in understanding how folic acid deficiency in particular alters epigenetics of cells to cause defects in maternal physiology and fetal and placental development. We are trying to understand what epigenetic changes are made in these cells and whether these changes can be passed from one generation to the next."


Above: Mouse embryo and placenta at embryonic (E) day 10.5.