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Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health

Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health
Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health
Previously, we have shown that a maternal low protein diet, fed exclusively during the preimplantation period of mouse development (Emb-LPD), is sufficient to induce by the blastocyst stage a compensatory growth phenotype in late gestation and postnatally, correlating with increased risk of adult onset cardiovascular disease and behavioural dysfunction. Here, we examine mechanisms of induction of maternal Emb-LPD programming and early compensatory responses by the embryo. Emb-LPD induced changes in maternal serum metabolites at the time of blastocyst formation (E3.5), notably reduced insulin and increased glucose, together with reduced levels of free amino acids (AAs) including branched chain AAs leucine, isoleucine and valine. Emb-LPD also caused reduction in the branched chain AAs within uterine fluid at the blastocyst stage. These maternal changes coincided with an altered content of blastocyst AAs and reduced mTORC1 signalling within blastocysts evident in reduced phosphorylation of effector S6 ribosomal protein and its ratio to total S6 protein but no change in effector 4E-BP1 phosphorylated and total pools. These changes were accompanied by increased proliferation of blastocyst trophectoderm and total cells and subsequent increased spreading of trophoblast cells in blastocyst outgrowths. We propose that induction of metabolic programming following Emb-LPD is achieved through mTORC1signalling which acts as a sensor for preimplantation embryos to detect maternal nutrient levels via branched chain AAs and/or insulin availability. Moreover, this induction step associates with changes in extra-embryonic trophectoderm behaviour occurring as early compensatory responses leading to later nutrient recovery
mouse blastocyst, trophectoderm, amino acids, maternal low protein diet, developmental programming, mTORC1
1932-6203
e52791
Eckert, Judith J.
729bfa49-7053-458d-8e84-3e70e4d98e57
Porter, Richard
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Watkins, Adam J.
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Burt, Elizabeth
55bfe055-dbe8-4819-a521-1cb526ea773a
Brooks, Suzanne E.
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Leese, Henry J.
0aee3eba-6732-4568-8f3f-93b3222c0b88
Humpherson, Peter G.
a73c0b15-ce4b-4c88-82be-f278111ecda0
Cameron, Iain T.
f7595539-efa6-4687-b161-e1e93ff710f2
Eckert, Judith J.
729bfa49-7053-458d-8e84-3e70e4d98e57
Porter, Richard
0b2cddd4-bca2-4548-b1be-e5f4b3cd43f5
Watkins, Adam J.
2d535c61-2df0-4410-a1b4-3aa1be5a43bb
Burt, Elizabeth
55bfe055-dbe8-4819-a521-1cb526ea773a
Brooks, Suzanne E.
4b0ecd34-a592-46b3-a21f-f83bdda46c7b
Leese, Henry J.
0aee3eba-6732-4568-8f3f-93b3222c0b88
Humpherson, Peter G.
a73c0b15-ce4b-4c88-82be-f278111ecda0
Cameron, Iain T.
f7595539-efa6-4687-b161-e1e93ff710f2

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)

Record type: Article

Abstract

Previously, we have shown that a maternal low protein diet, fed exclusively during the preimplantation period of mouse development (Emb-LPD), is sufficient to induce by the blastocyst stage a compensatory growth phenotype in late gestation and postnatally, correlating with increased risk of adult onset cardiovascular disease and behavioural dysfunction. Here, we examine mechanisms of induction of maternal Emb-LPD programming and early compensatory responses by the embryo. Emb-LPD induced changes in maternal serum metabolites at the time of blastocyst formation (E3.5), notably reduced insulin and increased glucose, together with reduced levels of free amino acids (AAs) including branched chain AAs leucine, isoleucine and valine. Emb-LPD also caused reduction in the branched chain AAs within uterine fluid at the blastocyst stage. These maternal changes coincided with an altered content of blastocyst AAs and reduced mTORC1 signalling within blastocysts evident in reduced phosphorylation of effector S6 ribosomal protein and its ratio to total S6 protein but no change in effector 4E-BP1 phosphorylated and total pools. These changes were accompanied by increased proliferation of blastocyst trophectoderm and total cells and subsequent increased spreading of trophoblast cells in blastocyst outgrowths. We propose that induction of metabolic programming following Emb-LPD is achieved through mTORC1signalling which acts as a sensor for preimplantation embryos to detect maternal nutrient levels via branched chain AAs and/or insulin availability. Moreover, this induction step associates with changes in extra-embryonic trophectoderm behaviour occurring as early compensatory responses leading to later nutrient recovery

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More information

Published date: 2012
Keywords: mouse blastocyst, trophectoderm, amino acids, maternal low protein diet, developmental programming, mTORC1
Organisations: Faculty of Medicine, Centre for Biological Sciences

Identifiers

Local EPrints ID: 346257
URI: http://eprints.soton.ac.uk/id/eprint/346257
ISSN: 1932-6203
PURE UUID: cecf423a-aa71-4c28-a622-614fa026c975
ORCID for Iain T. Cameron: ORCID iD orcid.org/0000-0002-4875-267X

Catalogue record

Date deposited: 14 Dec 2012 12:31
Last modified: 17 Dec 2019 01:55

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