母体循环中的miRNAs通过改变胎盘转录组和胎儿血管动力学来促进负面妊娠结果
Marisa R Pinson1, Alexander M Tseng1, Tenley E Lehman1
1Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, TX, United States of America.
PloS one
|November 6, 2023
概括
母体循环中的microRNAs (miRNAs) 可以预测妊娠并发症. 向怀孕的小鼠注射特定的升高的miRNAs通过损害胎盘血流和改变基因表达来减少胎儿生长.
科学领域:
- 生殖生物学 生殖生物学
- 发育生物学是发展生物学.
- 分子生物学分子生物学
背景情况:
- 孕妇血液中循环的microRNAs (miRNAs) 是妊娠并发症和不良分娩结果的潜在生物标志物.
- 孕期增加的母体循环miRNAs (HEamiRNAs) 与婴儿生长缺陷和胎盘发育有关.
- 产前酒精暴露是已知的子宫内生长限制 (IUGR) 的风险因素.
研究的目的:
- 调查HEamiRNAs在调解IUGR中的因果作用.
- 确定HEamiRNA给药对胎盘功能和胎儿发育的影响.
- 在胎盘中识别受HEamiRNAs影响的分子通路.
主要方法:
- 在孕期第10天向孕期小鼠静脉注射组合的小鼠保存的HEamiRNAs.
- 评估带血流量,胎儿体重和头骨生长指数.
- 胎儿胎盘的RNA测序 (RNAseq) 用于分析转录基因变化.
- 权重基因共同表达网络分析以确定关键信号通路.
主要成果:
- 单次使用HEamiRNAs显著减弱了带血流,导致IUGR (胎儿体重降低和头骨生长).
- RNAseq揭示了胎儿胎盘中持久的转录基因变化,包括Notch通路 (Dll4,Rfng,Hey1) 的上调.
- 权重基因共同表达网络分析确定了化学激素信号作为胎儿生长和头部大小的预测因素.
结论:
- 在妊娠期间服用的HEamiRNAs可以通过损害胎盘血管生成和带血流直接引起IUGR.
- 这些miRNA诱导了胎盘基因表达的显著和持久的变化,影响了对发育至关重要的途径.
- 这些发现突出了HEamiRNAs作为预防或治疗IUGR的潜在治疗点.
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