Kretschmer, Tobias and Turnwald, Eva-Maria and Thiele, Antje and Kallage, Ciara and Neweling, Lena and Kammerer, Merlin and Janoschek, Ruth and Zentis, Peter and Handwerk, Marion and Wohlfarth, Maria and Kalis, Simone and Nusken, Eva and Nusken, Kai-Dietrich and Bae-Gartz, Inga and Köninger, Angela and Gellhaus, Alexandra and Grundemann, Dirk and Hucklenbruch-Rother, Eva and Dotsch, Jorg and Alcazar, Miguel A. Alejandre and Appel, Sarah (2025) 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. PLACENTA, 171. pp. 91-101. ISSN 0143-4004, 1532-3102
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Introduction: 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. Methods: 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. Results: 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 gamma-H2AX 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. Discussion: 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OBESOGENIC DIET; OBESITY; EXPRESSION; WOMEN; HEALTH; Maternal obesity; Placenta; Calcification; Oxidative stress; Endothelial DNA damage; Placental fetal vasculature |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Geburtshilfe) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Apr 2026 09:06 |
| Last Modified: | 17 Apr 2026 09:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67710 |
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