Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta.
Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta.
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DOI：
10.1371/journal.pone.0047986
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Junien C
中科院分区：
文献类型：
--
作者：
Gabory A;Ferry L;Fajardy I;Jouneau L;Gothié JD;Vigé A;Fleur C;Mayeur S;Gallou-Kabani C;Gross MS;Attig L;Vambergue A;Lesage J;Reusens B;Vieau D;Remacle C;Jais JP;Junien C
男性和女性对妊娠期营养过剩的反应为随后成人发病的非传染性疾病的性别差异奠定了基础。胎盘素作为一种广泛认可的编程剂，有助于基础过程。根据我们之前的研究结果，妊娠期间的高脂肪饮食会引发 CpG 和整个基因组内性别特异性的表观遗传改变，以及印记基因簇的失调。我们进一步研究了饮食和性别对小鼠胎盘组织学、转录组和表观遗传特征的影响。在整个胎盘中，基础基因表达和对母体高脂肪饮食的反应均呈性别二态性。许多基因表现出性别二态性表达，但无论饮食如何，只有 11 个基因表现出性别二态性表达。与性染色体基因的关键作用一致，其中 3 个基因是 Y 特异性的，3 个是 X 特异性的。在高脂肪饮食下差异表达的所有基因中，只有 16 个基因在男性和女性中均受到一致影响。这些差异不仅是数量上的，而且是质量上的显着差异。失调基因的生物学功能和网络在两性之间存在显着差异。由于饮食、性别或两者兼有的影响，表观遗传机制的七个基因失调，包括 Y 连锁和 X 连锁组蛋白去甲基化酶旁系同源物 Kdm5c 和 Kdm5d，它们可以标记不同的男性和女性表观基因组。 DNA甲基转移酶辅因子Dnmt3l基因表达受到影响，让人想起我们之前观察到的整体DNA甲基化的变化。总体而言，编程轨迹的这种显着的性别二态性对当前的饮食干预方案进行了相当大的修改。
Males and females responses to gestational overnutrition set the stage for subsequent sex-specific differences in adult onset non communicable diseases. Placenta, as a widely recognized programming agent, contibutes to the underlying processes. According to our previous findings, a high-fat diet during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes. We further investigated the impact of diet and sex on placental histology, transcriptomic and epigenetic signatures in mice. Both basal gene expression and response to maternal high-fat diet were sexually dimorphic in whole placentas. Numerous genes showed sexually dimorphic expression, but only 11 genes regardless of the diet. In line with the key role of genes belonging to the sex chromosomes, 3 of these genes were Y-specific and 3 were X-specific. Amongst all the genes that were differentially expressed under a high-fat diet, only 16 genes were consistently affected in both males and females. The differences were not only quantitative but remarkably qualitative. The biological functions and networks of genes dysregulated differed markedly between the sexes. Seven genes of the epigenetic machinery were dysregulated, due to effects of diet, sex or both, including the Y- and X-linked histone demethylase paralogues Kdm5c and Kdm5d, which could mark differently male and female epigenomes. The DNA methyltransferase cofactor Dnmt3l gene expression was affected, reminiscent of our previous observation of changes in global DNA methylation. Overall, this striking sexual dimorphism of programming trajectories impose a considerable revision of the current dietary interventions protocols.
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影响因子：
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作者：
Coan, P. M.;Vaughan, O. R.;Fowden, A. L.
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.0504468103
发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0913843107
发表时间：
2010-02-23
影响因子：
11.1
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Gutierrez-Adan, A.