ABSTRACT

MicroRNAs (miRNAs) are increasingly seen as important regulators of placental development and opportunistic biomarker targets. Given the difficulty in obtaining samples from early gestation and subsequent paucity of the same, investigation of the role of miRNAs in early gestation human placenta has been limited. To address this, we generated miRNA profiles using 96 placentas from presumed normal pregnancies, across early gestation, in combination with matched profiles from maternal plasma. Placenta samples range from 6 to 23 weeks’ gestation, a time period that includes placenta from the early, relatively low but physiological (6–10 weeks’ gestation) oxygen environment, and later, physiologically normal oxygen environment (11–23 weeks’ gestation).

We identified 637 miRNAs with expression in 86 samples (after removing poor quality samples), showing a clear gestational age gradient from 6 to 23 weeks’ gestation. We identified 374 differentially expressed (DE) miRNAs between placentas from 6–10 weeks’ versus 11–23 weeks’ gestation. We see a clear gestational age group bias in miRNA clusters C19MC, C14MC, miR-17 ~ 92 and paralogs, regions that also include many DE miRNAs. Proportional change in expression of placenta-specific miRNA clusters was reflected in maternal plasma.

The presumed introduction of oxygenated maternal blood into the placenta (between ~10 and 12 weeks’ gestation) changes the miRNA profile of the chorionic villus, particularly in placenta-specific miRNA clusters. Data presented here comprise a clinically important reference set for studying early placenta development and may underpin the generation of minimally invasive methods for monitoring placental health.

摘要

MicroRNAs (miRNAs) 越来越被视为胎盘发育和机会性生物标志物靶标的重要调节剂。鉴于从早期妊娠中获取样本的困难和随后的样本缺乏，对 miRNA 在早期妊娠人胎盘中的作用的研究受到限制。为了解决这个问题，我们使用来自假定正常妊娠的 96 个胎盘生成 miRNA 谱，跨越早期妊娠，并结合来自母体血浆的匹配谱。胎盘样本的范围从妊娠 6 到 23 周，这个时间段包括从早期的胎盘，相对较低但生理的（6-10 孕周）氧环境，以及后来的生理正常氧环境（11-23 孕周） ）。

我们在 86 个样本中鉴定了 637 个 miRNAs 表达（去除劣质样本后），显示从 6 到 23 周妊娠的明显胎龄梯度。我们在妊娠 6-10 周与妊娠 11-23 周的胎盘之间鉴定了 374 个差异表达 (DE) miRNA。我们在 miRNA 簇 C19MC、C14MC、miR-17 ~ 92 和旁系同源物（也包括许多 DE miRNA）的区域中看到了明显的孕龄组偏差。胎盘特异性 miRNA 簇表达的比例变化反映在母体血浆中。

假定将含氧母体血液引入胎盘（妊娠约 10 至 12 周）会改变绒毛膜绒毛的 miRNA 谱，尤其是胎盘特异性 miRNA 簇。这里提供的数据包括用于研究早期胎盘发育的临床重要参考集，并可能支持用于监测胎盘健康的微创方法的产生。