Kumar Awanit, Sharma Sourabh, Costantine Maged M, Rood Kara, Urrabaz-Garza Rheanna, Jacob Jeena, Richardson Lauren S, Kammala Ananth Kumar, Menon Ramkumar
Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, The Ohio State University College of Medicine, 395 W. 12Th Ave, 5Th Floor, Columbus, OH, USA.
Placenta. 2025 Feb;160:118-125. doi: 10.1016/j.placenta.2025.01.001. Epub 2025 Jan 3.
Adverse pregnancies outcomes present a clinical dilemma in Perinatal medicine. This is partly due to lack of accuracy of current biomarkers to predict high-risk pregnancies at an earlier stage. The placental alkaline phosphatase (PLAP) carrying extracellular vesicles (EVs), and their cargo have been reported as a source of biomarkers for placental health and an indication of pre-eclampsia progression.
We postulate that PLAP is not only placental but also expressed in other fetal organs, suggesting that PLAP + ve EVs are not only a functional indicator of placental function alone.
We evaluated PLAP in the placenta, fetal membranes, maternal decidua, myometrial cells, and the EVs derived from them. Various bioanalytical techniques were used to detect PLAP expressions in the cells and EVs. The EVs were characterized by size/quantity, PLAP as a cargo, and canonical EV protein markers.
PLAP expression was determined in the chorion trophoblast cells (CTCs) of the fetal membranes and the placental trophoblasts; however, it was absent in the amnion layer of the fetal membranes and the maternal uterine cells used in this study. Using multiple experimental approaches, we further verified the cellular sources of PLAP and confirmed that the EVs from the chorion and placental trophoblasts contain PLAP.
Our studies suggest that PLAP is not truly placental. Instead, cells of trophoblast lineage in both fetal membranes and the placenta express PLAP in cells and their EVs. Although PLAP + ve EVs for biomarkers are not exclusively placental, they still represent real-time fetal-specific tissues conditions during pregnancy.
不良妊娠结局是围产期医学中的一个临床难题。部分原因是当前生物标志物在早期预测高危妊娠时缺乏准确性。携带细胞外囊泡(EVs)的胎盘碱性磷酸酶(PLAP)及其所载物质已被报道为胎盘健康生物标志物的来源及子痫前期进展的指标。
我们推测PLAP不仅存在于胎盘,还在其他胎儿器官中表达,这表明PLAP阳性的细胞外囊泡不仅仅是胎盘功能的功能性指标。
我们评估了胎盘、胎膜、母体蜕膜、子宫肌层细胞以及从中衍生的细胞外囊泡中的PLAP。使用了各种生物分析技术来检测细胞和细胞外囊泡中PLAP的表达。通过大小/数量、作为所载物质的PLAP以及典型的细胞外囊泡蛋白标志物对细胞外囊泡进行表征。
在胎膜的绒毛滋养层细胞(CTCs)和胎盘滋养层细胞中确定了PLAP的表达;然而,在本研究中使用的胎膜羊膜层和母体子宫细胞中未检测到PLAP。通过多种实验方法,我们进一步验证了PLAP的细胞来源,并确认来自绒毛膜和胎盘滋养层细胞的细胞外囊泡含有PLAP。
我们的研究表明PLAP并非真正只存在于胎盘。相反,胎膜和胎盘中的滋养层谱系细胞在细胞及其细胞外囊泡中均表达PLAP。虽然用于生物标志物的PLAP阳性细胞外囊泡并非仅来源于胎盘,但它们仍代表孕期实时的胎儿特异性组织状况。