Tris(2-chloroethyl) Phosphate Leads to Unbalanced Circulating Erythrocyte in Mice by Activating both Medullary and Extramedullary Erythropoiesis

Tris(2-chloroethyl) phosphate (TCEP), a prevalent organophosphorus flame retardant, has been identified in various environmental matrices and human blood samples, provoking alarm regarding its hematological toxicity, a subject that has not been thoroughly investigated. Red blood cells (RBCs), or erythrocytes, are the predominant cell type in peripheral blood and are crucial for the maintenance of physiological health. This investigation employed oral gavage to examine the effects of TCEP exposure on erythrocyte counts in mice and to clarify the underlying mechanisms. The results demonstrated a marked increase in circulating RBC counts post-TCEP exposure, concomitantly heightening the risk of polycythemia vera (PV). TCEP exposure stimulated erythropoiesis across all stages of medullary development, including the differentiation of hematopoietic stem cells into erythroid progenitors, the progression of erythrocyte development, and the maturation of erythrocyte. Moreover, TCEP potentiated extramedullary erythropoiesis in the spleen and liver. Subsequent bioinformatics analysis implied that TCEP-induced erythropoiesis was attributed to p53 downregulation. Thus, these findings indicate that TCEP disrupts erythrocyte-mediated hematological homeostasis through the enhancement of both medullary and extramedullary erythropoiesis, leading to the alteration of hematological equilibrium.