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

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.