Woldeamanuel Gashaw Garedew, Tlaye Kenean Getaneh, Wang Xueqin, Nguyen-Hoang Long, Zhou Qiongjie, Wang Yinan, Leung Bo Wah, Wang Yao, Poon Liona C, Wang Chi Chiu
Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.
Department of Biomedical Sciences, School of Medicine, Wolkite University, Wolkite, Ethiopia.
BMC Med. 2025 Jun 9;23(1):346. doi: 10.1186/s12916-025-04132-9.
Platelets play critical roles in the pathogenesis of preeclampsia, including thrombosis, endothelial dysfunction and inflammation. However, preeclampsia-associated changes in platelet gene expression and activation at the maternal-foetal interface remain unknown. Moreover, aspirin nonresponsiveness in high-risk pregnancies underscores the need for low-cost biomarkers to identify nonresponders. Nevertheless, the changes of platelet indices in women who develop preeclampsia despite aspirin prophylaxis have not yet been evaluated. In this study, we aimed to investigate the changes in platelet indices associated with aspirin nonresponsiveness, activation state and transcriptional landscape in preeclampsia.
Platelet indices were compared between aspirin-responsive and nonresponsive women. Logistic regression analysis was performed to determine the associations between platelet indices and aspirin nonresponsiveness. Opal immunofluorescence staining was performed to evaluate the expression of platelet-specific (CD42b) and activation (CD62P) markers in placental villous and decidual tissues. RNA sequencing (RNA-seq) was performed to investigate the transcriptomic profile of platelets.
A decrease in platelet count (PC) during the second trimester as well as an increase in mean platelet volume (MPV) and a lower PC/MPV ratio in the third trimester were significantly associated with the subsequent development of aspirin nonresponsiveness. We observed significantly greater expression of CD62P in the placental villous and CD42b in the decidua of the preeclamptic group than in those of the nonpreeclamptic group. Colocalization analysis of CD42b and CD62P revealed that the preeclamptic placenta and decidua presented significant platelet activation. RNA-seq analysis revealed a total of 20, 618 and 1819 transcripts in the peripheral blood, placental villous and decidua of preeclamptic women, respectively. Functional analysis revealed that the PI3K-Akt and Wnt signalling pathways were significantly enriched in the placental villous and decidua of preeclamptic patients, respectively. RT‒qPCR analysis confirmed the upregulation of FKBP5, LAMA5, FZD5 and FGG mRNA expression in preeclampsia.
Our findings suggest that PC in the second trimester and PC, MPV and PC/MPV ratio in the third trimester may be useful for assessing aspirin nonresponsiveness in women at high risk of preeclampsia. Furthermore, our findings demonstrate that preeclampsia is associated with increased platelet activation and significant enrichment of signalling pathways involved in platelet activation.
血小板在子痫前期的发病机制中发挥关键作用，包括血栓形成、内皮功能障碍和炎症反应。然而，子痫前期相关的血小板基因表达变化以及母胎界面处血小板的激活情况仍不清楚。此外，高危妊娠中阿司匹林无反应性凸显了需要低成本生物标志物来识别无反应者。尽管如此，尽管进行了阿司匹林预防仍发生子痫前期的女性血小板指标变化尚未得到评估。在本研究中，我们旨在调查子痫前期中与阿司匹林无反应性、激活状态和转录图谱相关的血小板指标变化。
比较阿司匹林反应者和无反应者的血小板指标。进行逻辑回归分析以确定血小板指标与阿司匹林无反应性之间的关联。采用欧泊免疫荧光染色评估胎盘绒毛和蜕膜组织中血小板特异性（CD42b）和激活（CD62P）标志物的表达。进行RNA测序（RNA-seq）以研究血小板的转录组图谱。
孕中期血小板计数（PC）降低以及孕晚期平均血小板体积（MPV）增加和PC/MPV比值降低与随后的阿司匹林无反应性显著相关。我们观察到子痫前期组胎盘绒毛中CD62P的表达以及蜕膜中CD42b的表达显著高于非子痫前期组。CD42b和CD62P的共定位分析显示子痫前期胎盘和蜕膜存在显著的血小板激活。RNA-seq分析分别在子痫前期女性的外周血、胎盘绒毛和蜕膜中发现了总共20、618和1819个转录本。功能分析显示PI3K-Akt和Wnt信号通路分别在子痫前期患者的胎盘绒毛和蜕膜中显著富集。RT-qPCR分析证实子痫前期中FKBP5、LAMA5、FZD5和FGG mRNA表达上调。
我们的研究结果表明，孕中期的PC以及孕晚期的PC、MPV和PC/MPV比值可能有助于评估子痫前期高危女性的阿司匹林无反应性。此外，我们的研究结果表明子痫前期与血小板激活增加以及参与血小板激活的信号通路显著富集有关。
