Morales-Roselló José, Martínez-Hernández Ana Isabel, Scheel Julia, Loscalzo Gabriela, García-López Eva María, Murdoch Colin
Department of Obstetrics and Gynecology, University and Polytechnical Hospital La Fe, Valencia, Spain.
Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain.
Biomed Hub. 2025 Jul 17;10(1):134-151. doi: 10.1159/000546518. eCollection 2025 Jan-Dec.
Micro-RNAs (miRNAs) participate in different biological processes, including fetal hypoxia. In this work, we aimed to evaluate the existence of a miRNA differential expression profile in maternal blood of pregnancies affected with late-onset fetal growth restriction (LO-FGR).
In a prospective study, a group of 35 fetuses were evaluated with Doppler ultrasound after 36 weeks. These included 15 fetuses with LO-FGR defined as fetal birth weight <10th centile plus a cerebroplacental ratio (CPR) <0.6765 MoM and 20 normal fetuses (normal BW plus a normal CPR). Afterward, for every pregnancy, maternal blood plasma was collected at birth, miRNAs were extracted, and full miRNA sequencing was performed using 20 of the indicated samples (12 with LO-FGR and 8 normal), determining the existence of differentially expressed miRNAs. Finally, this differential expression was validated in a wider population of 35 fetuses by means of quantitative reverse transcription polymerase chain reaction.
Full mRNA sequencing showed that FGR mothers expressed differential expression of several miRNA. The highest differences were seen for miR-486-5p/3p, miR-516a/b-5p, miR-19a/b-3p, miR-296-5p, miR-10b-5p, miR-205-5p, and Let-7g-5p. However, PCR validation only confirmed significant differences in miR-486-5p/3p.
Mothers delivering FGR fetuses express a miRNA profile, which includes differential expression of miR-486-5p/3p. This information might improve our understanding of the pathophysiological processes involved in late-onset FGR. Future validation and feasibility studies will be required to propose maternal blood miRNAs as a valid tool in the diagnosis and management of FGR.
微小RNA(miRNA)参与包括胎儿缺氧在内的不同生物学过程。在本研究中,我们旨在评估晚发性胎儿生长受限(LO-FGR)妊娠孕妇血液中miRNA差异表达谱的存在情况。
在一项前瞻性研究中,对36周后35例胎儿进行多普勒超声检查。其中包括15例LO-FGR胎儿,定义为胎儿出生体重低于第10百分位数且脑胎盘比率(CPR)<0.6765倍中位数(MoM),以及20例正常胎儿(正常出生体重加正常CPR)。之后,对于每例妊娠,在出生时采集孕妇血浆,提取miRNA,并对20个指定样本(12例LO-FGR和8例正常)进行全miRNA测序,以确定差异表达miRNA的存在情况。最后,通过定量逆转录聚合酶链反应在另外35例胎儿的更大样本中验证这种差异表达。
全mRNA测序显示,FGR孕妇表达多种miRNA的差异表达。miR-486-5p/3p、miR-516a/b-5p、miR-19a/b-3p、miR-296-5p、miR-10b-5p、miR-205-5p和Let-7g-5p的差异最为明显。然而,PCR验证仅证实了miR-486-5p/3p存在显著差异。
分娩FGR胎儿的孕妇表达一种miRNA谱,其中包括miR-486-5p/3p的差异表达。这些信息可能有助于我们更好地理解晚发性FGR所涉及的病理生理过程。未来需要进行进一步的验证和可行性研究,以提出将孕妇血液中的miRNA作为FGR诊断和管理的有效工具。