Assessment of the impact of oxidative stress and inflammation on placental angiogenesis in women with gestational diabetes mellitus (GDM)

Gestational diabetes mellitus (GDM) is defined by maternal hyperglycemia, yet growing evidence indicates that it is a systemic disorder involving oxidative stress, inflammation, endothelial dysfunction and altered placental angiogenesis. The placenta plays a central role in translating maternal metabolic disturbances into fetal and vascular consequences. This narrative review aimed to synthesize current experimental and clinical evidence on the role of oxidative stress and inflammation in the regulation of placental angiogenesis in GDM. The reviewed studies consistently demonstrate that pregnancies complicated by GDM are characterized by increased oxidative stress and inflammatory activity at both systemic and placental levels. These disturbances are associated with endothelial dysfunction and dysregulation of angiogenic signaling, leading to abnormal placental vascular remodeling. Genetic susceptibility primarily influences maternal glucose metabolism, while placental oxidative and angiogenic alterations appear to develop downstream of metabolic stress and are further modulated by epigenetic mechanisms. Collectively, these processes contribute to the characteristic placental phenotype of GDM and may underlie fetal programming and long-term cardiometabolic risk in the offspring. Importantly, evidence from randomized trials and meta-analyses indicates that antioxidant-oriented interventions can partially improve redox balance, inflammatory status, and metabolic indices in women with GDM. Current evidence suggests that oxidative stress may represent a central link between maternal hyperglycemia and placental vascular dysfunction in GDM. Beyond glycemic control, targeting redox imbalance and inflammatory pathways may represent a potential complementary strategy to improve placental function and pregnancy outcomes. Integration of oxidative, inflammatory, and angiogenic biomarkers into future longitudinal studies may facilitate biological stratification of GDM and support the development of more personalized therapeutic approaches.