Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo's potential, affecting adult health

Tom P. Fleming*, Adam J. Watkins, Congshan Sun, Miguel A. Velazquez, Neil R. Smyth, Judith J. Eckert

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)684-692
Number of pages9
JournalReproduction, fertility and development
Volume27
Issue number4
DOIs
Publication statusPublished - 3 Mar 2015

Bibliographical note

Funding: Biotechnology and Biological Sciences Research Council (BB/I001840/1, BB/F007450/1), The Medical Research Council (G9800781), the NICHD National Cooperative Program (U01 HD044635) and the EU-FP7 EpiHealth and EpiHealthNet programs.

Keywords

  • blastocyst
  • cardiometabolic disease
  • endocytosis
  • mammalian target of rapamycin complex signalling
  • primitive endoderm
  • trophectoderm

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