Centre for Biological Sciences

Research project: Maternal mechanisms induced by diet regulating embryo developmental plasticity affecting life-long health

Project type: Other

These studies focus on the maternal mechanisms inducing potentially detrimental developmental programming in the embryo. They will provide a powerful resource for developing dietary/pharmacological strategies to combat adverse gestational induction of disease.

Currently Active: Yes

Project Overview

Mouse blastocyst

Mouse blastocyst

Mouse blastocyst

The incidences of adult cardiovascular and metabolic diseases are increasing worldwide at epidemic rates. Studies show that conditions of prenatal life, for instance the quality of maternal nutrition, relate strongly to the risk of such diseases. Tom Fleming’s work, using rodent models, has demonstrated that the earliest stage of embryo development, pre-implantation, is highly sensitive to maternal nutrient levels. Poor maternal protein nutrition can change the embryo’s development so as to increase its survival chances. This is called 'developmental plasticity', but it can ultimately lead to an increased risk of cardiovascular and metabolic disease in later adult life. New data on IVF children who may also have experienced relatively poor nutrient conditions as embryos in culture, show increased risk of elevated blood pressure and metabolic disorders. More recently, Tom Fleming’s research has focused on the mechanisms of embryo response to poor maternal diet and how these change the subsequent developmental programme. Discovering what induces developmental plasticity in embryos, would allow the devising of preventative strategies against adverse health outcomes.
Tom Fleming’s work indicates that the mother utilises the composition of amino acids and possibly insulin within the uterine lumen to communicate to the embryo that nutrient levels are poor which then provokes developmental plasticity. Using an embryo in vitro culture model developed to mimic conditions within the uterine lumen he will attempt to modulate this communication pathway and determine precisely the molecular configuration of amino acids and insulin that provoke embryo responses.
A second part of Professor Flemings study concerns the mechanism mediated by the mother in response to poor maternal diet. Preliminary data has shown that the uterine wall is induced to generate an increased supply of blood vessels in response to poor diet around the time of implantation. This discovery raises a new concept that the mother can enhance nutrient delivery in response to poor diet in early gestation. This maternal response will be characterised fully and assessed whether it is a direct response to dietary signals within the mother or induced through a signal mediated by the embryo. We will also assess, in quantitative terms, the contribution made by enhanced uterine vascularisation on embryo and fetal survival and growth relative to other aspects of embryo developmental plasticity.
These studies focus on the maternal mechanisms inducing potentially detrimental developmental programming in the embryo. They will provide a powerful resource for developing dietary/pharmacological strategies to combat adverse gestational induction of disease.

Funding: BBSRC
Funding duration: May 2011 - May 2014

 

Related research groups

Publications

Publications associated with this project from The University of Southampton's electronic library (e-prints):


Key Publications

Fleming, T.P., Velazquez, M.A., Eckert, J.J., Lucas, E.S. and Watkins, A.J. (2012) Nutrition of females during the peri-conceptional period and effects on foetal programming and health of offspring. [in special issue: Reproductive Health Management of Sheep and Goats] Animal Reproduction Science, 130, (3-4), 193-197. (doi:10.1016/j.anireprosci.2012.01.015). (PMID:22341375).
Lucas, E.S., Watkins, A.J., Cox, A.L., Marfy-Smith, S.J., Smyth, N. and Fleming, T.P. (2011) Tissue-specific selection of reference genes is required for expression studies in the mouse model of maternal protein undernutrition. Theriogenology, 76, (3), 558-569. (doi:10.1016/j.theriogenology.2011.03.008). (PMID:21550104).
Sun, C., Velazquez, M.A., Marfy-Smith, S., Sheth, B., Cox, A., Johnston, D.A., Smyth, N. and Fleming, T.P. (2014) Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition. Development, 141, (5), 1140-1150. (doi:10.1242/dev.103952). (PMID:24504338).
Sellayah, Dyan, Dib, Lea, Anthony, Frederick W., Watkins, Adam J., Fleming, Tom P., Hanson, Mark A. and Cagampang, Felino R. (2014) Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring. European Journal of Nutrition, 1-9. (doi:10.1007/s00394-014-0657-4). (PMID:24481689).
Eckert, Judith J., Porter, Richard, Watkins, Adam J., Burt, Elizabeth, Brooks, Suzanne E. , Leese, Henry J., Humpherson, Peter G. and Cameron, Iain T. (2012) Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health. PLoS ONE, 7, (12), e52791. (doi:10.1371/journal.pone.0052791). (PMID:23300778).
Fleming, Tom P., Lucas, Emma S., Watkins, Adam J. and Eckert, Judith J. (2011) Adaptive responses of the embryo to maternal diet and consequences for post-implantation development. Reproduction, Fertility and Development, 24, (1), 35-44. (doi:10.1071/RD11905). (PMID:22394716).
Watkins, Adam J., Lucas, Emma S., Wilkins, Adrian, Cagampang, Felino R.A. and Fleming, Tom P. (2011) Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age. PLoS ONE, 6, (12), e28745. (doi:10.1371/journal.pone.0028745). (PMID:22194901).
Barker, D.J., Barker, M., Fleming, T. and Lampl, M. (2013) Developmental biology: support mothers to secure future public health. Nature, 504, 209-211. (doi:10.1038/504209a). (PMID:24350368).

Staff

Members of staff associated with this project: