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

循环 microRNA 作为妊娠合并糖尿病的胎盘和胎儿生长的新型调节因子

• 批准号: MR/R023166/1
• 负责人: Karen Forbes
• 金额: $ 68.1万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR023166%2F1
• 关键词: Circulating; microRNAs; novel; regulators; placental

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.

患有糖尿病的母亲所生的婴儿往往比正常大。这可能会在出生时给婴儿和母亲造成问题和/或新生儿疾病研究在小鼠和患有糖尿病母亲所生的孩子中也表明，怀孕期间暴露于糖尿病的婴儿在年龄较大时患肥胖症或糖尿病或心脏病的风险增加。目前还不知道这是什么原因，但我们知道糖尿病患者的胎盘更大。在怀孕期间，血液中存在被称为miRNAs的分子，但我们发现，其中一些分子，包括一种被称为miR-375的分子，在患有糖尿病的孕妇中会增加。我们先前已经证明，在正常妊娠中，miRNAs帮助胎盘生长，所以我们认为糖尿病妇女中高水平的miR-375可能导致胎盘变得太大。其他研究表明，miR-375对成人胰岛素的产生和维持正常的血糖水平很重要。我们认为，母亲体内这些高水平的miR-375可能也会影响婴儿的胰岛素水平，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在成年后是否有可能患糖尿病，来观察母亲血液中这种miRNA的高水平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miRNAs对婴儿生长的影响，并确定这是否会影响他们以后的健康，我们需要给母亲注射miRNAs，然后测试其效果。目前还不可能在人类身上做到这一点，所以我们将给怀孕的小鼠注射miRNAs，然后观察出生体重。我们还将观察血压，并测试后代是否会在以后的生活中患上糖尿病。当我们做完这些实验后，我们就会知道妈妈血液中的miRNAs是否导致胎盘和婴儿变大，和/或它们是否导致婴儿长大后患上糖尿病。如果像我们怀疑的那样，这些miRNAs参与其中，我们应该能够设计出减少血液中这些miRNAs的治疗方法。这最终将减少糖尿病的短期和长期影响，并降低婴儿成年后患肥胖症、心血管疾病或糖尿病的机会。

项目成果

miR-1-3p and miR-133-3p are altered in maternal serum EVs and placenta in pregnancies complicated by gestational diabetes with large-for-gestational age babies

妊娠期大于胎龄儿并发妊娠糖尿病时，母体血清 EV 和胎盘中 miR-1-3p 和 miR-133-3p 发生改变

• DOI: 10.1530/endoabs.65.p349
• 发表时间: 2019
• 期刊: Endocrine Abstracts
• 作者: Kennedy M

MIR-1-3P and MIR-133A-3P are altered in pregnancies complicated by GDM and LGA, and levels are associated with placental vascular maturity

MIR-1-3P 和 MIR-133A-3P 在妊娠合并 GDM 和 LGA 时发生改变，其水平与胎盘血管成熟度相关

• DOI: 10.1016/j.placenta.2022.03.118
• 发表时间: 2022
• 期刊: Placenta
• 影响因子: 3.8
• 作者: Kennedy M

Glucose Treatment Targets in Pregnancy - A Review of Evidence and Guidelines.

妊娠期血糖治疗目标 - 证据和指南回顾。

• DOI: 10.2174/1573399818666220422083935
• 发表时间: 2023
• 期刊: Current diabetes reviews
• 影响因子: 3.3
• 作者: Byford AR

Temporal fluctuations in maternal glucose levels alter placental transcriptome in pregnancies complicated by gestational diabetes

妊娠糖尿病合并妊娠时，母体血糖水平的时间波动会改变胎盘转录组

• DOI: 10.1016/j.placenta.2021.07.209
• 发表时间: 2021
• 期刊: Placenta
• 影响因子: 3.8
• 作者: Byford A

Interaction between Glucose, Extracellular Vesicles and Placenta Function in Gestational Diabetes

妊娠糖尿病中葡萄糖、细胞外囊泡和胎盘功能之间的相互作用

• DOI: 10.1016/j.jri.2023.104001
• 发表时间: 2023
• 期刊: Journal of Reproductive Immunology
• 影响因子: 3.4
• 作者: Forbes K