特定的血浆 microRNA 谱可能是胚胎移植后生化妊娠丢失的潜在非侵入性生物标志物。

Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer.

机构信息

Reproductive Center of Gynecology and Obstetrics Department, NanFang Hospital, Southern Medical University, Guangzhou, 510515, China.

Department of Reproductive Medicine Center, Foshan Maternal and Child Health Care Hospital, Southern Medical University, Foshan, 528000, China.

出版信息

BMC Pregnancy Childbirth. 2024 May 8;24(1):351. doi: 10.1186/s12884-024-06488-x.

DOI:10.1186/s12884-024-06488-x

PMID:38720272

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11080217/

Abstract

BACKGROUND

Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL.

METHODS

In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~~14 and ultrasound at day28~~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR.

RESULTS

BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes.

CONCLUSION

Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.

摘要

背景

血浆 microRNAs 可作为预测和诊断疾病的生物标志物。目前尚未建立可靠的非侵入性生化妊娠丢失生物标志物。我们旨在分析着床期前后 microRNA 动态谱，并探讨血浆 microRNAs 是否可作为预测生化妊娠丢失的非侵入性生物标志物。

方法

本研究收集了胚胎移植（ET）日（ET0）、ET 后 11 天（ET11）和 ET 后 14 天（ET14）接受 ET 的患者的血浆样本。根据 ET 后 11~~14 天血清 hCG 水平和 ET 后 28~~35 天超声结果，将患者分为 NP（阴性妊娠）、BPL（生化妊娠丢失）和 CP（临床妊娠）组。采用 miRNA 测序检测不同时间点的 microRNA 谱。我们分析了着床期前后 BPL 的血浆 microRNA 特征，描述了着床期 microRNA 动态变化，构建了 microRNA 共表达网络，并建立了 BPL 的预测模型。最后，通过 Taqman RT-qPCR 验证测序结果。

结果

BPL 患者在着床期多个时间点的血浆 microRNA 谱与 CP 患者明显不同。机器学习模型显示，血浆 microRNAs 可预测 BPL。RT-qPCR 证实 miR-181a-2-3p、miR-9-5p、miR-150-3p、miR-150-5p 和 miR-98-5p、miR-363-3p 在不同生殖结局患者之间存在显著差异表达。