Prenatal PM2.5 exposure affects embryonic hematopoietic development through SOX2-regulated gene expression.

Fine particulate matter (PM2.5) is one of the most concerning air pollutants, with emerging evidence indicating that it can negatively impact embryonic development and lead to adverse birth outcomes. Hematopoiesis is a critical process essential for the survival and normal development of the embryo, consisting of three temporally overlapping stages and involving multiple hematopoietic loci, including the yolk sac and fetal liver. Therefore, we hypothesized that abnormal embryonic hematopoietic development can significantly influence developmental outcomes. In this study, we established a prenatal PM2.5 exposure model and observed decreased embryo weights and elevated platelet counts at embryonic day 18.5 (E18.5). Additionally, we employed flow cytometry and colony-forming unit assays, which revealed a significant decrease in the proliferative differentiation potential of erythro-myeloid progenitors in the E10.5 yolk sac, as well as a reduction in both the number and function of hematopoietic stem progenitor cells in the E14.5 fetal liver. Through bioinformatic analysis, we identified that these alterations are associated with several typical biological processes and genes regarding cell proliferation, cell differentiation, response to hypoxia, and regulation of hematopoiesis. Importantly, via quantitative real-time PCR, chromatin immunoprecipitation, and immunofluorescence, we further elucidated that prenatal exposure to PM2.5 affects embryonic hematopoiesis by regulating the expression of SOX2, an important transcription factor involved in embryonic development, along with its related genes. Collectively, these findings provide experimental evidence supporting the necessity for controlling regional PM2.5 exposure to promote child well-being in polluted areas.