Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo's potential, affecting adult health
Tom P. Fleming A F , Adam J. Watkins A E , Congshan Sun A C , Miguel A. Velazquez A D , Neil R. Smyth A and Judith J. Eckert B
+ Author Affiliations
- Author Affiliations
A Centre for Biological Sciences, University of Southampton, Southampton SO16 6YD, UK.
B Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
C Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
D School of Agriculture, Food and Rural Development, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK.
E Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
F Corresponding author. Email: tpf@soton.ac.uk
Reproduction, Fertility and Development 27(4) 684-692 https://doi.org/10.1071/RD14455
Submitted: 20 November 2014 Accepted: 3 February 2015 Published: 3 March 2015
Abstract
Periconceptional environment may influence embryo development, ultimately affecting adult health. Here, we review the rodent model of maternal low-protein diet specifically during the preimplantation period (Emb-LPD) with normal nutrition during subsequent gestation and postnatally. This model, studied mainly in the mouse, leads to cardiovascular, metabolic and behavioural disease in adult offspring, with females more susceptible. We evaluate the sequence of events from diet administration that may lead to adult disease. Emb-LPD changes maternal serum and/or uterine fluid metabolite composition, notably with reduced insulin and branched-chain amino acids. This is sensed by blastocysts through reduced mammalian target of rapamycin complex 1 signalling. Embryos respond by permanently changing the pattern of development of their extra-embryonic lineages, trophectoderm and primitive endoderm, to enhance maternal nutrient retrieval during subsequent gestation. These compensatory changes include stimulation in proliferation, endocytosis and cellular motility, and epigenetic mechanisms underlying them are being identified. Collectively, these responses act to protect fetal growth and likely contribute to offspring competitive fitness. However, the resulting growth adversely affects long-term health because perinatal weight positively correlates with adult disease risk. We argue that periconception environmental responses reflect developmental plasticity and ‘decisions’ made by embryos to optimise their own development, but with lasting consequences.
Additional keywords: blastocyst, cardiometabolic disease, endocytosis, mammalian target of rapamycin complex signalling, primitive endoderm, trophectoderm.
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