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bioRxiv · 10.1101/2025.04.14.648714

Disrupted stemness and redox homeostasis in mesenchymal stem cells of neonates from mothers with obesity: implications for increased adiposity

Bellalta, S.·Pinheiro Machado, E.·Prins, J.·Plosch, T.·Casanello, P.·Faas, M.
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Abstract

Maternal obesity is a risk factor for increased fetal adiposity. The underlying mechanisms remain unclear, however, emerging evidence suggests that mesenchymal stem cells (MSCs), which are the precursors of adipocytes, from neonates of mothers with obesity exhibit enhanced adipogenic differentiation potential. We hypothesise that the MSCs of neonates from mothers with obesity have different stemness potential and redox state compared to the MSCs from mothers with normal weight. MSCs were isolated from neonates of women with obesity (BMI>30 kg/m{superscript 2}, OB-MSCs) and women with normal weight (BMI <25 kg/m{superscript 2}, NW-MSCs). OB-MSCs showed reduced stemness potential, as seen by a lower OCT3/4 expression and lower clonogenic capacity, than NW-MSCs (p<0.05). In addition, OB-MSCs showed higher levels of mitochondrial superoxide (O2*-), together with lower antioxidant SOD2 gene expression, compared to NW-MSCs (p<0.05). Conversely, OB-MSCs had higher levels of glutathione (GSH) compared to NW-MSCs (p<0.05). Upon exposure to H2O2 (250 M), OB-MSCs displayed attenuated antioxidant response, with lower SOD1, SOD2 and GPX1 gene expression as compared to NW-MSCs (p<0.05). Upon exposure to higher oxidative stress (H2O2, 400 M), total ROS levels were lower in OB-MSCs than in NW-MSCs. In contrast, when challenged for mitochondrial ROS, OB-MSCs showed higher levels of mitochondrial superoxide production as compared to NW-MSCs (p<0.05). Our results indicate that OB-MSCs have lower stemness potential, elevated mitochondrial O2*- and a different basal and oxidative stress-induced redox profile compared to NW-MSCs. These changes in OB-MSCs could predispose them to an increase adipogeneic commitment. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/648714v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1638346org.highwire.dtl.DTLVardef@3f9caaorg.highwire.dtl.DTLVardef@46925eorg.highwire.dtl.DTLVardef@1336dfa_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Bellalta, S., Pinheiro Machado, E., Prins, J., Plosch, T., Casanello, P., Faas, M.. 2025-04-19. Disrupted stemness and redox homeostasis in mesenchymal stem cells of neonates from mothers with obesity: implications for increased adiposity. https://doi.org/10.1101/2025.04.14.648714

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