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.
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DOI：
10.1371/journal.pone.0052791
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fleming TP
中科院分区：
文献类型：
--
作者：
Eckert JJ;Porter R;Watkins AJ;Burt E;Brooks S;Leese HJ;Humpherson PG;Cameron IT;Fleming TP
以前，我们已经表明，母体低蛋白饮食，喂养专门在植入前时期的小鼠发展（Emb-LPD），是足以诱导囊胚阶段的补偿性生长表型在妊娠后期和产后，与成年发病的心血管疾病和行为功能障碍的风险增加。在这里，我们研究了母体Emb-LPD编程和胚胎早期补偿反应的诱导机制。Emb-LPD在胚泡形成时（E3.5）诱导母体血清代谢物的变化，显著降低胰岛素和增加葡萄糖，以及降低游离氨基酸（AA）水平，包括支链AA亮氨酸、异亮氨酸和缬氨酸。Emb-LPD还导致囊胚期子宫液中支链AA减少。这些母体变化与胚泡AA含量的改变和胚泡内mTORC 1信号传导的减少相一致，这在效应子S6核糖体蛋白磷酸化的减少及其与总S6蛋白的比率中是明显的，但在效应子4 E-BP 1磷酸化和总库中没有变化。这些变化伴随着囊胚滋养外胚层和总细胞的增殖增加，以及随后囊胚生长物中滋养层细胞的扩散增加。我们认为，诱导代谢编程后，Emb-LPD是通过mTORC 1信号传导，作为一个传感器植入前胚胎检测母体营养水平，通过支链氨基酸和/或胰岛素的可用性。此外，这一诱导步骤与胚胎外滋养外胚层行为的变化有关，这些变化是早期的补偿反应，导致后来的营养恢复。
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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影响因子：
16
作者：
Düvel K;Yecies JL;Menon S;Raman P;Lipovsky AI;Souza AL;Triantafellow E;Ma Q;Gorski R;Cleaver S;Vander Heiden MG;MacKeigan JP;Finan PM;Clish CB;Murphy LO;Manning BD
通讯作者：
Manning BD
DOI：
10.1073/pnas.0308560101
发表时间：
2004-04-20
影响因子：
11.1
作者：
Fernández-Gonzalez, R;Moreira, P;Gutiérrez-Adán, A
通讯作者：
Gutiérrez-Adán, A
影响因子：
3.8
作者：
Groebner, Anna E.;Rubio-Aliaga, Isabel;Ulbrich, Susanne E.
通讯作者：
Ulbrich, Susanne E.
影响因子：
3.8
作者：
Basatemur, E.;Sutcliffe, A.
通讯作者：
Sutcliffe, A.
影响因子：
5.5
作者：
Coan, P. M.;Vaughan, O. R.;Fowden, A. L.
通讯作者：
Fowden, A. L.