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Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease

Watkins, Adam J., Ursell, Elizabeth, Panton, Rose, Papenbrock, Thomas, Hollis, Lisa, Cunningham, Colm, Wilkins, Adrian, Perry, V.Hugh, Sheth, Bhavwanti, Kwong, Wing Yee, Eckert, Judith Joana, Wild, Arthur E., Hanson, Mark A., Osmond, Clive and Fleming, Tom P. (2008) Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease Biology of Reproduction, 78, (2), pp. 299-306. (doi:10.1095/biolreprod.107.064220). (PMID:17989357).

Record type: Article


Poor maternal nutrition during pregnancy can alter postnatal phenotype and increase susceptibility to adult cardiovascular and metabolic diseases. However, underlying mechanisms are largely unknown. Here, we show that maternal low protein diet (LPD), fed exclusively during mouse preimplantation development, leads to offspring with increased weight from birth, sustained hypertension, and abnormal anxiety-related behavior, especially in females. These adverse outcomes were interrelated with increased perinatal weight being predictive of later adult overweight and hypertension.

Embryo transfer experiments revealed that the increase in perinatal weight was induced within blastocysts responding to preimplantation LPD, independent of subsequent maternal environment during later pregnancy. We further identified the embryo-derived visceral yolk sac endoderm (VYSE) as one mediator of this response. VYSE contributes to fetal growth through endocytosis of maternal proteins, mainly via the multiligand megalin (LRP2) receptor and supply of liberated amino acids.

Thus, LPD maintained throughout gestation stimulated VYSE nutrient transport capacity and megalin expression in late pregnancy, with enhanced megalin expression evident even when LPD was limited to the preimplantation period. Our results demonstrate that in a nutrient-restricted environment, the preimplantation embryo activates physiological mechanisms of developmental plasticity to stablize conceptus growth and enhance postnatal fitness. However, activation of such responses may also lead to adult excess growth and cardiovascular and behavioral diseases.

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e-pub ahead of print date: 7 November 2007
Published date: 1 February 2008
Keywords: behavior, blastocyst, blood pressure, conceptus, developmental biology, embryo, environment, growth, low protein diet, megalin, preimplantation embryo, yolk sac
Organisations: Dev Origins of Health & Disease, Biomedicine


Local EPrints ID: 148583
PURE UUID: 9a949881-1e66-430d-aaa1-2a36bd53f043
ORCID for Clive Osmond: ORCID iD

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Date deposited: 14 May 2010 12:47
Last modified: 18 Jul 2017 19:31

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Author: Adam J. Watkins
Author: Elizabeth Ursell
Author: Rose Panton
Author: Thomas Papenbrock
Author: Lisa Hollis
Author: Colm Cunningham
Author: Adrian Wilkins
Author: V.Hugh Perry
Author: Bhavwanti Sheth
Author: Wing Yee Kwong
Author: Arthur E. Wild
Author: Mark A. Hanson
Author: Clive Osmond ORCID iD
Author: Tom P. Fleming

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