Abstract
Gestational diabetes mellitus (GDM) significantly disrupts placental structure and function, leading to complications such as intrauterine growth restriction (IUGR) and preeclampsia. This study aimed to investigate the effects of GDM on placental histology, angiogenesis, and oxidative stress, as well as evaluate metformin's protective role in mitigating these changes. A total of 60 pregnant Sprague-Dawley rats were divided into four groups: control, metformin-treated, GDM, and GDM with metformin. GDM was induced using streptozotocin (STZ) at 40mg/kg, and metformin was administered at 200mg/kg from gestational day (GD) 4 to GD17. Blood glucose and insulin levels were assessed, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated. Placentae were weighed and subjected to histological, immunohistochemical, and molecular analyses, focusing on key angiogenesis markers (VEGF, VEGFR, CD31, KLF2) and oxidative stress indicators (MDA, eNOS). GDM increased placental weight, angiogenesis (elevated VEGF, VEGFR, CD31), and oxidative stress (elevated MDA, eNOS). Histopathological changes included villous edema, membrane rupture, and hemosiderin deposition. Metformin treatment reduced placental weight; normalized VEGF, KLF2, and PlGF expression; and improved placental architecture. Additionally, oxidative stress was significantly reduced in metformin-treated GDM rats. In conclusion, GDM induces placental abnormalities, promoting excessive angiogenesis and oxidative stress, potentially leading to IUGR and other complications. Metformin showed protective effects by reducing placental overgrowth and restoring vascular and oxidative balance. These findings suggest that metformin may play a therapeutic role in improving placental health in GDM pregnancies, warranting further investigation into its long-term effects on fetal development and maternal health.
Published Version
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