Work

Maternal body composition and the placental-fetal unit under maternal high-fat feeding partially improve by metformin treatment or lifestyle interventions during pregnancy in a mouse model

Year: 2025

Type: article

Abstract: Studies showed that metabolic imbalances during pregnancy in obesity impair the maternal-fetal axis, resulting in fetal growth disturbances with higher risk later in life. Since research has linked many of maternal and fetal sequelae to placental dysfunction, we tested if treatment with an anti-diabetic drug (metformin) or lifestyle interventions improve maternal body weight, placental status or fetal growth. Mice were either fed a control or high-fat diet. After mating, high-fat diet mice were split into 4 subgroups, 1 received no intervention while the other 3 received either metformin treatment, a nutritional intervention (NI) or an exercise intervention (RUN). At gestational day 15.5, mice were sacrificed. All interventions improved body weight of high-fat diet dams, but only NI and RUN maintained fetal growth compared to HFD. Investigation of the placenta showed that (i) NI reduced lipid accumulation in the labyrinth zone (LZ) but neither NI nor RUN attenuated calcification and oxidative stress. Endothelial gammaH2AX staining was decreased in the LZ by both NI and RUN. (ii) Metformin did not attenuate lipid accumulation in the LZ, placental calcification and oxidative stress, however, protein levels of the endothelial cell marker CD31 were restored in whole placenta lysates. No changes were detected for fetal vessel capillary surface or length of the LZ under any intervention group. Although all tested interventions had beneficial effects on the mother and the placental-fetal unit, NI seems to be most promising. Our findings highlight that preventive strategies for women with obesity should aim for pre-counseling advisory service. In particular, NI and RUN protected from endothelial stress response and metformin was vasculo-protective, offering strategies to preserve the physiological placental-fetal unit and materno-fetal nutrient supply. thumb down: negative impact of HFD-induced maternal obesity on the parameter analysed.thump up: improvement by intervention on the parameter analysed compared to HFD alone.(thumb up) calcification: indicates an improvement that was not statistically significant (p-value < 0.05) but showed a trend (p-value < 0.01).(thump up) fetal body weight: indicates an improvement that was not statistically significant (p-value < 0.05) in both analyses (individual fetal weights and mean fetal litter weights).Metformin intervention: metformin treatment during pregnancy via drinking water.Nutritional intervention: switching to a healthy diet during pregnancy.Exercise intervention: performing exercise in a running wheel during pregnancy.Created in BioRender. • diet-induced maternal obesity impairs placental integrity and fetal growth • metformin and lifestyle interventions (switching to a healthy diet or performing exercise) during pregnancy improve maternal body weight • switching to a healthy diet during pregnancy ameliorates placental damage • lifestyle interventions improve fetal body weight

Source: Placenta

DOI: 10.1016/j.placenta.2025.09.016