Blood Serum From Obese Women Raises ROS Production by Neural Stem Cells

Abstract

Maternal obesity has been associated with adverse pregnancy outcomes and altered fetal development, but the direct influence of circulating maternal factors on early human neural cells remains poorly understood. Neural stem cells (NSCs) provide a controlled system to examine how metabolic and inflammatory changes may affect early neurodevelopment. We differentiated human embryonic stem cells into NSCs and exposed them to 10% serum from non-obese or obese women. Cell viability, oxidative stress, metabolic activity, proliferation, and neural marker expression were evaluated. Metabolomic profiling confirmed distinct serum signatures between donor groups, particularly involving lipid and redox-related metabolites. Exposure to human serum, independent of donor phenotype, reduced viability, decreased Ki-67 and PAX6 expression, increased Caspase-3 and p53 labeling, and altered progenitor markers, indicating activation of stress pathways. Although overall responses to non-obese and obese serum were similar, NSCs exposed to obese serum showed a sustained increase in ROS and a transient elevation in resazurin reduction at later time points. These differences were modest but statistically significant and may reflect altered metabolic and redox handling. Together, the findings show that serum exposure imposes considerable stress on NSCs in vitro and that obesity-related factors may subtly amplify oxidative responses. The study also underscores the limitations of this artificial model and highlights the need for systems that more closely approximate physiological conditions during neurodevelopment.