Impact of PFOS Exposure on Murine Fetal Hematopoietic Stem Cells, Associated with Intrauterine Metabolic Perturbation

Abstract

This study hypothesized that perfluorooctanesulfonate (PFOS) exposure disrupts maternal-fetal metabolism, affecting fetal liver hematopoietic stem cell (FL-HSC) development. Pregnant mice received PFOS (0.3 and 3 μg/g bw) and were sacrificed on gestation day 14.5. Metabolomic analysis of maternal plasma revealed disruptions in steroid hormone, purine, carbohydrate, and amino acid metabolism, which aligned with the enriched pathways in amniotic fluid (AF). FL analysis indicated increased purine metabolism and disrupted glucose and amino acid metabolism. FL exhibited higher levels of polyunsaturated fatty acids, glycolytic and TCA metabolites, and pro-inflammatory cytokine IL-23, crucial for hematopoiesis regulation. Transcriptomic analysis of FL-HSCs revealed disturbances in the PPAR signaling pathway, pyruvate metabolism, oxidative phosphorylation, and amino acid metabolism, correlating with FL metabolic changes. Metabolomic analysis indicated significant rises in glycerophospholipid and vitamin B6 metabolism related to HSC expansion and differentiation. Flow cytometric analysis confirmed increased HSC populations and progenitor activation for megakaryocyte, erythrocyte, and lymphocyte lineages. The CFU assay showed a significant increase in BFU-E and CFU-G, but a decrease in CFU-GM in FL-HSCs from the H-PFOS group, indicating altered differentiation potential. These findings provide for the first time insights into the effects of PFOS on maternal-fetal metabolism and fetal hematopoiesis, highlighting implications for pollution-affected immune functions.