Effect of Metformin on a Preeclampsia-Like Mouse Model Induced by High-Fat Diet

BACKGROUND: Metformin has been reported to decrease insulin resistance and is associated with a lower risk of pregnancy-induced hypertension and preeclampsia. It is widely accepted that the placenta plays a crucial role in the development of preeclampsia. Our aim is to explore the effect of metformin on preeclampsia. STUDY DESIGN: We examined control diet-fed (isocaloric diet) pregnant mice (CTRL group), pregnant mice fed a high-fat diet (HF group), and high-fat-diet-fed pregnant mice treated with metformin (HF-M group). The HF mice were fed a high-fat diet six weeks before pregnancy to establish a preeclampsia-like model; then, the group was randomly divided into a HF group and a HF-M group after pregnancy. Blood pressure, urine protein, pregnancy outcomes, protein expression, and histopathological changes in the placentas of all groups were examined and statistically analysed. RESULTS: We observed that metformin significantly improved high blood pressure, proteinuria, and foetal and placental weights in the HF-M group compared with the HF group. Metformin significantly improved placental labyrinth and foetal vascular development in preeclampsia. In addition, metformin effectively increased matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) levels in the placenta. CONCLUSIONS: Our results suggest that metformin can improve preeclamptic symptoms and pregnancy outcomes.