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The University of Southampton
Biological Sciences

Research project: Linking perturbed maternal environment during periconceptional development, due to diabetes, obesity or assisted reproductive technologies, and altered health during ageing

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Mechanisms by which assisted conception treatments may affect embryo development and health into adulthood.

Mouse preimplantation embryo
Mouse preimplantation embryo

Scientific evidence clearly indicates that ageing and health in adult life are programmed by genetic and epigenetic mechanisms early in life. The working hypothesis of the current proposal is that (1) the critical "window" of this programming is periconception oocyte and embryonic development and that (2) molecular pathways involved in embryo metabolic and stress adaptation (Insulin/IGF, mTOR) restrict health and longevity. Developmental plasticity of mammalian embryos in response to the environment, including nutrient availability, demonstrates the capacity for newly emerging embryonic and extra-embryonic cell lineages to initiate compensatory responses which may attune nutrient delivery to the needs of the developing fetus. Developmental programming effects at the time of preimplantation embryo formation across species, including the human, make it imperative to investigate in detail mechanisms that protect against increased disease risk. EpiHealth will focus on these early events in several relevant models (diabetes, obesity and assisted reproductive technologies (ART)), using human samples, stem cell lines, animal models and data mining/bioinformatics tools to decipher the most important pathways and to offer options for early intervention to avoid adverse health effects, in excellent accordance with the call. Moreover, the EpiHealth ambition is to interpret the early stages of adverse developmental programming directly with the characteristics identified in a unique longevity database, the long-lived individuals database, to identify the key metabolic and genetic signatures linking developmental plasticity with the ageing process. Knowing the pathways critical in maintaining health in aged individuals informs us for the first time about are the critical pathways and epigenetic states to protect at the onset of development. Better knowledge of the developmental programming of societal mass diseases (diabetes and obesity pandemics) will allow the linking of human development with the ageing process, based on further understanding of its basic biology, and can realistically be expected to become the most important route towards disease prevention and suppression and to facilitate healthy ageing.

Funding: EU FP7 ‘EpiHealth'
Funding duration: Nov 2012 - Nov 2016

Related research groups

Biomedical Sciences

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