Hsu Te-Yao, Tsai Chih-Chang, Cheng Hsin-Hsin, Lan Kuo-Chung, Hung Hsuan-Ning, Huang Wan-Ting, Lai Yun-Ju, Huang Kun-Long, You Huey-Ling, Tsai Ping-Chung, Jan Chia-Ing, Li Sung-Chou
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan.
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan; Department of Obstetrics and Gynecology, Jen-Ai Hospital, Taichung, Taiwan.
Placenta. 2025 Jan;159:1-8. doi: 10.1016/j.placenta.2024.11.012. Epub 2024 Nov 22.
The overall prevalence of placenta accreta spectrum (PAS) is approximately 0.17 %, but it accounts for 7 % of maternal mortality and is associated with intraoperative and postoperative morbidity. The pathogenesis mechanisms of PAS include an imbalance between decidualization and trophoblast invasion. The aim of this study is to identify the pathogenesis roles of miR-34a in PAS.
For this purpose, we collected 15 placenta tissues from pregnant subjects with PAS complications and another 15 placenta tissues from normal pregnancy (NP) cases. Then, we conducted in situ hybridization assay to compare miR-34a expression level, followed by in vitro simulations of NP and PAS with miR-34a and scrambled control (SC) mimic transfection in cells, respectively. Next, we conducted in vitro cellular assays to investigate the pathogenesis mechanisms of miR-34a in PAS.
We first confirmed significantly lower level of miR-34a in the trophoblast villous (TV) from PAS patients. By in vitro assays, lower miR-34a led to significantly higher cell proliferation and enhanced cell migration in TV epithelial cells. In addition, lower miR-34a resulted in elevated angiogenesis ability in vascular endothelial cells. Finally, to identify the pathway involved by miR-34a in PAS, we used microarray (raw data available via NCBI GEO database with accession number GSE279257) and flow cytometry to confirm that lower miR-34a significantly repressed the apoptosis activity in TV epithelial cells.
In this study, we not only confirmed miR-34a as a biomarker of PAS but also clarified the in vitro pathogenesis mechanism of miR-34a in PAS.
胎盘植入谱系疾病（PAS）的总体患病率约为0.17%，但其占孕产妇死亡率的7%，并与术中及术后发病率相关。PAS的发病机制包括蜕膜化与滋养层细胞侵袭之间的失衡。本研究的目的是确定miR-34a在PAS中的发病机制作用。
为此，我们收集了15例患有PAS并发症的孕妇的胎盘组织以及另外15例正常妊娠（NP）病例的胎盘组织。然后，我们进行原位杂交试验以比较miR-34a的表达水平，随后分别在细胞中用miR-34a和乱序对照（SC）模拟物转染对NP和PAS进行体外模拟。接下来，我们进行体外细胞试验以研究miR-34a在PAS中的发病机制。
我们首先证实PAS患者的滋养层绒毛（TV）中miR-34a水平显著降低。通过体外试验，较低的miR-34a导致TV上皮细胞中细胞增殖显著增加且细胞迁移增强。此外，较低的miR-34a使血管内皮细胞的血管生成能力升高。最后，为了确定miR-34a在PAS中涉及的途径，我们使用微阵列（原始数据可通过NCBI GEO数据库获得，登录号为GSE279257）和流式细胞术来证实较低的miR-34a显著抑制TV上皮细胞中的凋亡活性。
在本研究中，我们不仅证实miR-34a是PAS的生物标志物，还阐明了miR-34a在PAS中的体外发病机制。
