Placental alkaline phosphatase (PLAP): Is it exclusively placental?

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.