Fetal manipulation of maternal metabolism is a critical function of Igf2 imprinting
Fetal manipulation of maternal metabolism is a critical function of Igf2 imprinting
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胎儿对母体代谢的操纵是 Igf2 印记的关键功能
DOI：
10.1101/2023.04.19.537510
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Lopez-Tello J
中科院分区：
文献类型：
--
作者：
Lopez-Tello J
哺乳动物中的母子互动主要是合作，但也有冲突。在进化过程中，胎儿已经进化到操纵母亲的生理机能，以增加通过胎盘的营养转移，但这些机制的特点很差。ImprintedIgf2（胰岛素样生长因子2）基因在具有内分泌功能的小鼠胎盘细胞中高度表达。在这里，我们表明，在小鼠中，这些细胞中Igf2的缺失导致受损的胎盘内分泌信号的母亲，但显着不会导致胎盘形态，生长或大小的变化。从机制上讲，我们发现Igf 2通过激素（包括催乳素）的缺陷产生，对于怀孕期间建立胰岛素抵抗状态以及将营养物质适当分配给发育中的胎儿至关重要。因此，胎儿生长受限和低血糖，由于受损的胎盘葡萄糖从母亲转移到胎儿。此外，胎盘内分泌细胞的Igf2缺失对后代肥胖和成年后的葡萄糖稳态具有长期影响。我们的研究为内在的胎儿操纵系统提供了长期寻求的令人信服的实验证据，该系统在胎盘中运作，以改变母体代谢和胎儿的资源分配，并对后代在以后的生活中的代谢健康产生影响。
Maternal-offspring interactions in mammals are mainly characterised by cooperation, but also conflict. Over evolutionary time, the fetus has evolved to manipulate the mother’s physiology to increase nutrient transfer through the placenta, but these mechanisms are poorly characterized. The imprintedIgf2(insulin-like growth factor 2) gene is highly expressed in mouse placental cells with endocrine functions. Here, we show that in the mouse, deletion ofIgf2in these cells leads to impaired placental endocrine signalling to the mother, but remarkably does not result in changes in placental morphology, growth or size. Mechanistically, we find thatIgf2via defective production of hormones, including prolactins, is essential for the establishment of the insulin-resistance state during pregnancy, and the appropriate partitioning of nutrients to the developing fetus. Consequently, fetuses are growth restricted and hypoglycemic, due to impaired placental glucose transfer from the mother to the fetus. Furthermore,Igf2loss from placental endocrine cells has long-lasting effects on offspring adiposity and glucose homeostasis in adult life. Our study provides long-sought compelling experimental evidence for an intrinsic fetal manipulation system, which operates in the placenta to modify maternal metabolism and resource allocation to the fetus, with consequences for offspring metabolic health in later life.
影响因子：
16
作者：
Kim, DH;Sarbassov, DD;Sabatini, DM
通讯作者：
Sabatini, DM
影响因子：
7.7
作者：
Musial B;Fernandez-Twinn DS;Vaughan OR;Ozanne SE;Voshol P;Sferruzzi-Perri AN;Fowden AL
通讯作者：
Fowden AL
影响因子：
7.7
作者：
Petry CJ;Evans ML;Wingate DL;Ong KK;Reik W;Constância M;Dunger DB
通讯作者：
Dunger DB