Maternal obesity, defined as a pregestational body mass index (BMI) of ≥30 kg/m², alters the intrauterine environment, thereby influencing fetal development. This thesis examines the impact of maternal obesity on mesenchymal stem cells (MSCs) derived from the Wharton’s jelly of neonatal umbilical cords, with a focus on early adipogenic programming. The central hypothesis of this thesis of Sofía Paz Bellalta Bremer posits that maternal obesity induces oxidative stress in MSCs, leading to dysregulation of the SIRT2-FOXO1-PPARγ signaling pathway, which in turn promotes enhanced adipogenesis.
The findings demonstrate that MSCs from neonates of obese mothers (OB-MSCs) exhibit reduced self-renewal capacity, lower pluripotency, and impaired clonogenic potential compared to MSCs from normal-weight mothers (NW-MSCs). OB-MSCs also display disrupted insulin signaling, increased oxidative stress, and compromised antioxidant defense mechanisms, including reduced superoxide dismutase activity. However, OB-MSCs exhibit compensatory adaptive mechanisms, such as elevated glutathione response under oxidative stress conditions.
Furthermore, the study identifies differential adipogenic potential in OB-MSCs, characterized by early activation of PPARγ and dysregulation of the FOXO1 pathway, facilitating a greater commitment toward adipocyte differentiation. Secretome analysis reveals a diminished basal redox state in OB-MSCs, accompanied by increased secretion of pro-inflammatory adipokines and lipogenic factors during adipogenesis.
In conclusion, maternal obesity induces oxidative stress and enhances the adipogenic potential of fetal MSCs, potentially contributing to an increased risk of adiposity in offspring. These findings provide critical insights into the early programming of adipose tissue and the role of maternal obesity in predisposing neonates to future metabolic dysfunction.
