IMPACT OF IN UTERO HYDROQUINONE EXPOSURE ON MATERNAL HEMATOPOIETIC STEM / PROGENITOR CELLS: ROLES OF CELL LINEAGES AND OXIDATIVE STRESS

Abstract

In utero benzene exposure increases fetal hematotoxicity risk; however, its effects on oxidative stress and lineage-specific alterations within the maternal hematopoietic stem/progenitor cell niche comprises of myeloid, lymphoid and erythroid lineages remain poorly defined and are addressed in this study. Briefly, pregnant mice (n=18) were divided into 3 groups, comprised of control and Hydroquinone (HQ)-treated groups. HQ, a benzene metabolite, was administered at 25 (HQ-25) and 50 (HQ-50) mg/kg body on gestational day (GD) 12, 14 and 16, followed by maternal bone marrow (BM) harvest on GD18. Then, colony-forming unit (CFU) assays were carried out to measure the clonogenicity status of myeloid, erythroid and pre-B lymphoid progenitors. Colonies-derived CFUs were counted and harvested for oxidative stress profile. HQ caused a significant reduction in colony counts for pre-B lymphoid progenitor at all HQ-exposed groups and erythroid progenitor at 50 mg/kg dosage (p<0.05).  However, the colony counts for myeloid progenitors are not significantly affected. Meanwhile, HQ significantly decreased (p<0.05) the glutathione (GSH) level only in myeloid progenitors, while no effect was observed in superoxide dismutase (SOD) level for other cell lineages. Oxidative stress markers were also influenced by cell lineages. HQ exposure significantly increased (p<0.05) the lipid peroxidation in erythroid progenitor cells and showed no remarkable effect on protein oxidation for all cell lineages. Conclusively, HQ exposure has the ability to induce oxidative damage in the maternal HSPCs niche, and the effect is dependent on hematopoietic cell lineages.