Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Blvd. 11, 8200 Aarhus, Denmark.
Department of Obstetrics and Gynaecology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 99, 8200 Aarhus, Denmark.
Int J Mol Sci. 2023 Oct 31;24(21):15826. doi: 10.3390/ijms242115826.
Clinically, unique markers in fetal membrane cells may contribute to the search for biomarkers for preterm prelabor rupture of the fetal membranes (pPROM) in maternal blood. pPROM is associated with overwhelming inflammation and premature cellular senescence causing "biological microfractures" of the fetal membranes. We hypothesize that these pathological processes are associated with the shedding of fetal membrane cells into the maternal circulation. The aim of this study was to identify markers expressed exclusively in fetal membrane cells to facilitate their isolation, characterization, and determination of biomarker potential in maternal blood. We have (1), by their transcriptomic profile, identified markers that are upregulated in amnion and chorion tissue compared to maternal white blood cells, and (2), by immunohistochemistry, confirmed the localization of the differentially expressed proteins in fetal membranes, placenta, and the placental bed of the uterus. RNA sequencing revealed 31 transcripts in the amnion and 42 transcripts in the chorion that were upregulated. Among these, 22 proteins were evaluated by immunohistochemistry. All but two transcripts were expressed both on mRNA and protein level in at least one fetal membrane cell type. Among these remaining 20 proteins, 9 proteins were not significantly expressed in the villous and extravillous trophoblasts of the placenta.
临床上,胎儿膜细胞中的独特标志物可能有助于在母血中寻找早产胎膜早破(pPROM)的生物标志物。pPROM 与强烈的炎症和过早的细胞衰老有关,导致胎儿膜的“生物微骨折”。我们假设这些病理过程与胎儿膜细胞脱落到母血循环有关。本研究的目的是鉴定仅在胎儿膜细胞中表达的标志物,以促进其分离、鉴定和确定母血中的生物标志物潜力。我们已经通过它们的转录组谱,鉴定了与母体白细胞相比在羊膜和绒毛膜组织中上调的标志物,并且通过免疫组织化学,确认了差异表达蛋白在胎儿膜、胎盘和子宫胎盘床中的定位。RNA 测序显示羊膜中有 31 个转录本和绒毛膜中有 42 个转录本上调。在这些转录本中,有 22 种蛋白质通过免疫组织化学进行了评估。除了两个转录本外,至少有一种胎儿膜细胞类型在 mRNA 和蛋白质水平上都表达了所有转录本。在剩下的 20 种蛋白质中,有 9 种蛋白质在胎盘的绒毛和绒毛外滋养细胞中没有明显表达。