子痫前期与胎盘中铁下垂生物标志物的表达改变有关,而与母体血管无关。

IF 2.5 3区 医学 Q2 OBSTETRICS & GYNECOLOGY
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI:10.1007/s43032-025-01935-2
Shu-Wing Ng, Allen C Ng, Michelle C Ng, Shu-Kay Ng, Felice Arcuri, Elizabeth M Genega, Jaclyn C Watkins, Drucilla J Roberts, Michael D House, Perrie F O'Tierney-Ginn, Daniel P Jacobsen, Anne C Staff, Errol R Norwitz
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引用次数: 0

摘要

铁凋亡是一种铁依赖性程序性细胞死亡机制,与子痫前期(PE)的发病机制有关。在这里,我们研究了主要的铁下垂生物标志物在胎盘和基底蜕膜组织中的表达。免疫组织化学(IHC)染色显示,在健康的cd31阳性胎盘内皮中,铁凋亡抑制因子、铁凋亡抑制蛋白1 (FSP1)和终产物丙二醛(MDA)高表达。三种标记物的染色在PE胎盘中均显著降低(P = 0.028)。体外研究表明,与滋养细胞、子宫内膜上皮细胞和间质成纤维细胞类型相比,永生化子宫内膜内皮细胞系及其胎儿对应物——人脐静脉内皮细胞,本质上对erastin诱导的铁系细胞死亡具有高度抗性。FSP1在子宫内膜内皮细胞中特异性表达。FSP1和另一种铁下垂抑制蛋白GPX4在细胞发生铁下垂细胞死亡时均被降解。有趣的是,在母体基底蜕膜组织中,这些相同标记物的染色没有显示内皮特异性染色,并且在健康组织和PE组织之间的染色没有显着差异。由于先前的研究表明子宫内膜细胞可以激活铁下垂产生促血管生成细胞因子,我们假设健康的胎盘内皮细胞激活铁下垂,如高MDA,促进血管发育而不发生细胞死亡,而PE胎盘显示铁下垂减少和血管发育不全。相比之下,健康组织和基底蜕膜肺组织都被认为处于铁下垂的静止阶段。进一步的研究是必要的,以调查铁下垂是如何调节在健康和PE妊娠。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preeclampsia is Associated with Altered Expression of Ferroptosis Biomarkers in Placental but not Maternal Vasculature.

Ferroptosis, an iron-dependent mechanism of programmed cell death, has been implicated in the pathogenesis of preeclampsia (PE). Here, we investigate the expression of key ferroptosis biomarkers in placental and decidua basalis tissues. Immunohistochemical (IHC) staining showed high expression of the ferroptosis suppressor, ferroptosis-suppressor protein 1 (FSP1), and the end product malondialdehyde (MDA), in healthy CD31-positive placental endothelium. The staining of all three markers was significantly reduced in PE placentas (P = 0.028). In vitro studies showed that an immortalized endometrial endothelial cell line, and its fetal counterpart, human umbilical vein endothelial cells, are intrinsically highly resistant to erastin-induced ferroptotic cell death compared with trophoblast, endometrial epithelial, and stromal fibroblast cell types. FSP1 was specifically expressed in the endometrial endothelial cells. Both FSP1 and another ferroptosis suppressor protein, GPX4, were degraded when the cells underwent ferroptotic cell death. Interestingly, staining of these same markers in maternal decidua basalis tissues did not show endothelium-specific staining, and no significant difference in staining was noted between healthy and PE tissues. Since previous studies have shown that endometrial cells can activate ferroptosis to produce pro-angiogenic cytokines, we posit that healthy placental endothelial cells activate ferroptosis, as evidenced by high MDA, to promote vasculature development without undergoing cell death, whereas PE placentas show reduced ferroptosis and vasculature underdevelopment. In contrast, both healthy and PE decidua basalis tissues were considered to be in a resting stage with regard to ferroptosis. Further studies are warranted to investigate how ferroptosis is regulated in both healthy and PE pregnancies.

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来源期刊
Reproductive Sciences
Reproductive Sciences 医学-妇产科学
CiteScore
5.50
自引率
3.40%
发文量
322
审稿时长
4-8 weeks
期刊介绍: Reproductive Sciences (RS) is a peer-reviewed, monthly journal publishing original research and reviews in obstetrics and gynecology. RS is multi-disciplinary and includes research in basic reproductive biology and medicine, maternal-fetal medicine, obstetrics, gynecology, reproductive endocrinology, urogynecology, fertility/infertility, embryology, gynecologic/reproductive oncology, developmental biology, stem cell research, molecular/cellular biology and other related fields.
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