Circulating microRNAs as novel regulators of placental and fetal growth in pregnancies complicated by maternal diabetes

患有糖尿病的母亲所生的婴儿通常比正常人大。这可能会导致婴儿和母亲在出生时出现问题，或者新生儿生病，对老鼠和患有糖尿病的母亲所生的孩子的研究也表明，怀孕期间接触糖尿病的婴儿长大后患肥胖、糖尿病或心脏病的风险更高。目前还不知道是什么原因导致的，但我们知道糖尿病患者的胎盘更大。在怀孕期间，血液中存在的mirna分子，但我们发现其中一些，包括miR-375，在患有糖尿病的孕妇中增加。我们之前的研究表明，在正常妊娠中，mirna有助于胎盘生长，因此我们认为糖尿病女性中miR-375的高水平可能导致胎盘生长过大。其他研究表明，miR-375对于成人胰岛素的产生和维持正常血糖水平很重要。我们认为母亲体内高水平的miR-375可能也会影响婴儿体内的胰岛素水平，这就是为什么他们更容易患糖尿病。我们将使用不同的技术来研究这种miRNA如何调节胎盘和婴儿的生长。然后，我们将通过测量血压和评估婴儿成年后是否有可能患上糖尿病，来观察母亲血液中这种高水平的miRNA是否会影响婴儿的健康。我们的研究将尽可能使用人类胎盘，然而，为了观察mirna对婴儿生长的影响，并确定这是否会影响他们以后的健康，我们需要给母亲提供mirna，然后测试效果。目前还不可能在人类身上做到这一点，所以我们将把mirna注入怀孕的老鼠体内，然后观察出生体重。我们还会观察他们的血压，并测试后代在以后的生活中是否会患上糖尿病。当我们完成这些实验后，我们将知道母亲血液中的mirna是否会导致胎盘和婴儿长大，以及/或者它们是否会导致婴儿长大后患上糖尿病。如果正如我们所怀疑的那样，这些mirna参与其中，我们应该能够设计出减少血液中这些mirna的治疗方法。这将最终减少糖尿病的短期和长期影响，并减少婴儿在成年后患肥胖症、心血管疾病或糖尿病的机会。

Babies born to mothers with diabetes are often bigger than normal. This can be a cause problems for the baby and mother at the time of birth and/or illness in the newborn Studies in mice and in children born to mothers with diabetes have also shown that babies exposed to diabetes in pregnancy have an increased risk of being obese or having diabetes or heart disease when they are older. Currently it isn't known what causes this, but we do know that the placentas from people with diabetes are bigger. During pregnancy molecules known as miRNAs that are present in blood but we have found that some of these including one known as miR-375, are increased in pregnant women with diabetes. We have previously shown that in normal pregnancy, miRNAs help the placenta to grow, so we think that high levels of miR-375 in women with diabetes, might be causing the placenta to grow too big. Other studies have shown that miR-375 is important for the production of insulin and maintaining normal blood sugar levels in adults. We think that these high levels of miR-375 in the mum might also be affecting insulin levels in the babies which is why they are more likely to develop diabetes. We will use different techniques to investigate how this miRNA regulates growth of the placenta and of the baby. We will then look to see if high levels of this miRNA in the mother's blood affect the health of the baby by measuring blood pressure and assessing whether they are likely to develop diabetes in adulthood. Our studies will use human placentas where possible, however to look at the effect of miRNAs on growth of the baby and to determine if this affects their health in later life, we will need to give miRNAs to the mother and then test the effect. It is currently not possible to do this in humans so we will give miRNAs to pregnant mice and then look at birth weight. We will also look at blood pressure and test whether the offspring develop diabetes in later life. When we have done these experiments we will know whether miRNAs in mum's blood are causing the placenta and baby to grow bigger and/or if they are responsible for the babies developing diabetes when they are older. If as we suspect, these miRNAs are involved, we should be able to design treatments to reduce these miRNAs in the blood. This will ultimately decrease the short and long term effects of diabetes and reduce the chance of babies developing obesity, cardiovascular disease or diabetes in adulthood.