Universität zu Köln

Kretschmer, Tobias ORCID: 0000-0002-4202-0806, Turnwald, Eva-Maria, Thiele, Antje, Kallage, Ciara, Neweling, Lena, Kammerer, Merlin, Janoschek, Ruth ORCID: 0000-0002-1332-9353, Zentis, Peter ORCID: 0000-0002-6999-132X, Handwerk, Marion, Wohlfarth, Maria, Kalis, Simone, Nüsken, Eva ORCID: 0000-0002-0674-804X, Nüsken, Kai-Dietrich ORCID: 0000-0001-5749-7183, Bae-Gartz, Inga ORCID: 0000-0002-4061-503X, Köninger, Angela, Gellhaus, Alexandra, Gründemann, Dirk ORCID: 0000-0003-0914-0299, Hucklenbruch-Rother, Eva ORCID: 0000-0002-8876-3533, Dötsch, Jörg ORCID: 0000-0003-1529-7647, Alejandre Alcazar, Miguel A. ORCID: 0000-0002-3176-0411 and Appel, Sarah ORCID: 0000-0003-0315-6513 (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. Elsevier. ISSN 0143-4004

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Abstract

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 (met- formin) 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 sub- groups, 1 received no intervention while the other 3 received either metformin treatment, a nutritional inter- vention (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
Creators:	Creators Email ORCID ORCID Put Code Kretschmer, Tobias UNSPECIFIED https://orcid.org/0000-0002-4202-0806 UNSPECIFIED Turnwald, Eva-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Kallage, Ciara UNSPECIFIED UNSPECIFIED UNSPECIFIED Neweling, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Kammerer, Merlin UNSPECIFIED UNSPECIFIED UNSPECIFIED Janoschek, Ruth UNSPECIFIED https://orcid.org/0000-0002-1332-9353 UNSPECIFIED Zentis, Peter UNSPECIFIED https://orcid.org/0000-0002-6999-132X UNSPECIFIED Handwerk, Marion UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlfarth, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalis, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Nüsken, Eva UNSPECIFIED https://orcid.org/0000-0002-0674-804X UNSPECIFIED Nüsken, Kai-Dietrich UNSPECIFIED https://orcid.org/0000-0001-5749-7183 UNSPECIFIED Bae-Gartz, Inga UNSPECIFIED https://orcid.org/0000-0002-4061-503X UNSPECIFIED Köninger, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Gellhaus, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Gründemann, Dirk UNSPECIFIED https://orcid.org/0000-0003-0914-0299 UNSPECIFIED Hucklenbruch-Rother, Eva UNSPECIFIED https://orcid.org/0000-0002-8876-3533 UNSPECIFIED Dötsch, Jörg UNSPECIFIED https://orcid.org/0000-0003-1529-7647 UNSPECIFIED Alejandre Alcazar, Miguel A. UNSPECIFIED https://orcid.org/0000-0002-3176-0411 UNSPECIFIED Appel, Sarah UNSPECIFIED https://orcid.org/0000-0003-0315-6513 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-810858
Identification Number:	10.1016/j.placenta.2025.09.016
Journal or Publication Title:	Placenta
Volume:	171
Page Range:	pp. 91-101
Number of Pages:	11
Date:	November 2025
Publisher:	Elsevier
ISSN:	0143-4004
Language:	English
Faculty:	Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin Faculty of Medicine > Pharmakologie > Instítut für Pharmakologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Maternal obesity ; Placenta ; Calcification ; Oxidative stress ; Endothelial DNA damage ; Placental fetal vasculature English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81085