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

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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.