Manganese porphyrin [MnTE-2-PyP]5+ improves maternal and offspring glycemic homeostasis, placental morphology, and redox balance in diabetic pregnant rats

Gestational Diabetes Mellitus (GDM) is a prevalent metabolic disorder during pregnancy, associated with oxidative stress and inflammation at systemic and placental levels. Manganese porphyrins (MnPs) modulate redox balance and inflammation, but their therapeutic potential in diabetic pregnants remains unexplored. This study investigated the effects of water-soluble MnP [MnTE-2-PyP]⁵⁺ (BMX-010, AEOL10113) on maternal and offspring glycemic parameters and placental alterations in a diabetic pregnant rat model induced by streptozotocin. MnP treatment was initiated on gestational day 10. Diabetic rats exhibited hyperglycemia, insulin resistance, impaired gestational and fetal mass gain, elevated plasma ALT and ALP, and decreased CK levels. MnP improved gestational mass gain, glucose tolerance, and insulin sensitivity in both mother and offspring, in addition to reducing maternal ALT and ALP levels and enhancing offspring mass gain. Histological analysis revealed that diabetes increased glycogen cell and cyst areas in the placental junctional zone and reduced fetal mesenchyme/trophoblast area in the labyrinth zone; MnP partially mitigated these alterations. At the maternal-fetal interface, diabetes elevated 8-OHdG, TBARS, ROS, HIF1α, IL-6, TNF-α, and SOD1, while downregulating Sod1, GPx1/2, Vegf, Plgf, Igf1, IL-10, and SOD enzymatic activity. MnP treatment decreased HIF1α and TBARS, increased SOD activity and catalase expression, and restored IL-10 expression at transcript and protein levels. These results indicate that MnP [MnTE-2-PyP]⁵⁺ improves maternal and offspring glycemic control, placental morphology, and redox homeostasis in diabetic pregnant rats, supporting its potential as a therapeutic strategy against diabetes-induced placental dysfunction.