Lipid Metabolism in Pregnancy: Adipose-Placental Interactions

胎生，或在父母体内发育活着的幼崽，是哺乳动物在早期生命的脆弱时期用来保护后代的一个基本生物学过程。为了支持胎生，哺乳动物进化出了一系列机制，允许将营养从母亲有效地转移到后代。一个关键的适应是胎盘的进化。胎盘是一个短暂的器官，具有多种功能，最终支持怀孕。在胎盘中，母体和胎儿的血液非常接近，允许营养物质和废物的交换。此外，胎盘产生的荷尔蒙向母亲的身体发出信号，并将她从食物中获得的营养引导到胎儿。哺乳动物的怀孕被认为包括两个阶段：怀孕早期，母亲增加食欲，以便将能量储存在脂肪仓库中；怀孕后期，母亲向快速成长的胎儿释放能量和营养。发育中的胎儿对某些营养素的需求特别高。其中一类营养素是必需脂肪酸(EFAs)。EFA在饮食中进入体内，它们在海洋生物中特别丰富，它们不能被哺乳动物合成。这些脂肪酸对大脑和眼睛的发育和发育是必不可少的。母体饮食中缺乏这些营养物质会导致人类失明和神经发育障碍。由于它们是如此重要，EFA在怀孕期间优先被输送到发育中的胎儿。然而，我们目前还不清楚母亲是如何做到这一点的，也不知道EFA是如何穿过胎盘屏障进入胎儿血液循环，从而用来建造大脑和眼睛的。在这个项目中，我们希望解释EFA是如何从母亲的饮食进入胎儿的。我们怀疑，EFA甚至在怀孕前就储存在母亲的脂肪储存中，在怀孕的后半段，它们被选择性地释放并运往肝脏，在那里它们被包装成一种可以被胎盘细胞识别的形式。在胎盘屏障，我们认为EFA是由一种特定的转运蛋白分子识别的，该转运蛋白分子可以将它们移动到细胞内。该项目的最后部分将研究胎盘如何与母亲沟通，使她从脂肪储存中释放脂肪。我们认为，特定的胎盘激素直接向母体脂肪发出信号，使那里的能量和营养物质在最佳时间被释放，以支持胎儿的生长。了解包括EFAs在内的脂肪酸是如何从母亲转移到胎儿的，这一点很重要，原因有几个。首先，这是一个基本的生物学过程，是所有哺乳动物繁殖的基础，从人类怀孕到牲畜饲养。其次，许多妇女营养不良，这一点在怀孕期间变得更加重要，因为母亲可能没有足够的营养储备来支持婴儿的健康发育。许多干预策略都试图增加给怀孕期间营养不良母亲的EFA数量，以试图改善婴儿的健康。然而，这些试验的结果好坏参半。为了充分支持健康妊娠、早期生命和终身健康，我们需要更多地了解胎盘和母亲沟通的过程，以确保足够的营养流动。

Viviparity, or the development of live young within the body of the parent, is a fundamental biological process that is used by mammals to protect their offspring during the vunerable period of early life. In order to support viviparity mammals have evolved a host of mechanisms to allow the efficient transfer of nutrition from mother to offspring. A crucial adaptation was the evolution of the placenta. The placenta is a transient organ with multiple functions that ultimately support pregnancy. In the placenta the maternal and fetal blood come into close proximity, allowing the exchange of nutrients and waste products. In addition, the placenta produces hormones that signal to the mother's body and direct the nutrients that she obtains from food toward the fetus.Pregnancy in mammals is thought to comprise of two phases; early pregnancy when the mother increases her appetite in order to store energy in her fat depots, and late pregnancy when she releases this energy and nutrients toward the rapidly growing fetus. Some nutrients are in particularly high demand by the developing fetus. One class of these nutrients are the essential fatty acids (EFAs). EFAs come into the body in the diet, they are particularly abundant in marine life, and they cannot be synthesised by mammals. These fatty acids are necessary for the development and growth of the brain and eye. Lack of these nutrients in the maternal diet causes blindness and neurodevelopmental disorders in humans. Because they are so important, EFAs are preferentially transported to the developing fetus during pregnancy. However, we currently do not understand how the mother achieves this, nor how EFAs cross the placental barrier to enter the fetal circulation so they can be used to build the brain and eye. In this project we hope to explain how EFAs travel from the maternal diet to the fetus. We suspect that EFAs are stored in maternal fat stores even prior to pregnancy, and that in the second half of pregnancy they are selectively released and travel to the liver where they are packaged into a form that can be recognised by placental cells. At the placental barrier we think that the EFAs are recognised by a specific transporter molecule that can move them inside the cells. The final part of the project will investigate how the placenta communicates with the mother so that she releases fats from her fat stores. We believe that specific placental hormones signal directly to the maternal fat to allow the energy and nutrients there to be liberated at the best time to support fetal growth.It is important to understand how fatty acids, including EFAs, are transferred from mother to fetus for several reasons. Firstly, this is a fundamental biological process that underlies all mammalian reproduction, from human pregnancy to livestock farming. Secondly, many women are poorly nourished and this becomes more important during pregnancy when the mother may have insufficient nutrient stores to support the healthy development of the baby. Many intervention strategies have tried to increase the amount of EFAs given to malnourished mothers in pregnancy to try to improve the health of the baby. However, these trials have met with mixed success. In order to fully support healthy pregnancy, early life and lifelong health, we need to understand much more about the processes by which the placenta and mother communicate to ensure adequate nutrient flow.