Placental protection of the fetal brain during short-term food deprivation
Placental protection of the fetal brain during short-term food deprivation
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DOI：
10.1073/pnas.1106022108
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发表时间：
2011-09-13
影响因子：
11.1
通讯作者：
Keverne, Eric B.
中科院分区：
文献类型：
--
作者：
Broad, Kevin D.;Keverne, Eric B.
胎儿基因组通过胎盘调节母体的生理和行为，胎盘产生的激素作用于母体的下丘脑。与此同时，胎儿本身也会发育出一个下丘脑。在这项研究中，我们发现许多调节胎盘发育的基因也调节发育中的下丘脑，在小鼠胚胎第12天和第13天(E12-13天)，这些基因的共同表达特别高。这种同步表达在一定程度上受到母系印记基因父系表达基因3(Peg3)的调节，该基因也在E12-13天的下丘脑和胎盘发育中共表达。我们进一步表明，用24小时的食物剥夺挑战下丘脑和胎盘的这种基因组连接会导致共表达基因的中断，主要是通过影响胎盘基因的表达。食物剥夺也会导致胎盘中Peg3基因表达的显著减少，其后果类似于许多由Peg3突变引起的胎盘基因变化。这种基因组失调不会发生在下丘脑，那里PEG3的表达随着食物的缺乏而增加。因此，食物匮乏带来的基因表达变化与胎儿基因组以牺牲胎盘为代价维持下丘脑发育是一致的。这种对胎盘基因失调的偏向改变与自噬和核糖体周转有关，而自噬和核糖体周转在短期内维持着发育中的下丘脑的营养供应。因此，在急性饥饿时期，胎儿通过短期牺牲胎盘来保护大脑发育，从而掌握自己的命运。
The fetal genome regulates maternal physiology and behavior via its placenta, which produces hormones that act on the maternal hypothalamus. At the same time, the fetus itself develops a hypothalamus. In this study we show that many of the genes that regulate placental development also regulate the developing hypothalamus, and in mouse the coexpression of these genes is particularly high on embryonic days 12 and 13 (days E12-13). Such synchronized expression is regulated, in part, by the maternally imprinted gene, paternally expressed gene 3 (Peg3), which also is developmentally coexpressed in the hypothalamus and placenta at days E12-13. We further show that challenging this genomic linkage of hypothalamus and placenta with 24-h food deprivation results in disruption to coexpressed genes, primarily by affecting placental gene expression. Food deprivation also produces a significant decrease in Peg3 gene expression in the placenta, with consequences similar to many of the placental gene changes induced by Peg3 mutation. Such genomic dysregulation does not occur in the hypothalamus, where Peg3 expression increases with food deprivation. Thus, changes in gene expression brought about by food deprivation are consistent with the fetal genome's maintaining hypothalamic development at a cost to its placenta. This biased change to gene dysregulation in the placenta is linked to autophagy and ribosomal turnover, which sustain, in the short term, nutrient supply for the developing hypothalamus. Thus, the fetus controls its own destiny in times of acute starvation by short-term sacrifice of the placenta to preserve brain development.