Kretschmer, Tobias ORCID: 0000-0002-4202-0806, Turnwald, Eva-Maria, Janoschek, Ruth, Wohlfarth, Maria, Handwerk, Marion, Doetsch, Joerg, Hucklenbruch-Rother, Eva and Appel, Sarah ORCID: 0000-0003-0315-6513 (2022). Treatment of high fat diet-induced obese pregnant mice with IL-6 receptor antibody does not ameliorate placental function and fetal growth restriction. Am. J. Reprod. Immunol., 88 (1). HOBOKEN: WILEY. ISSN 1600-0897

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Abstract

Problem : Pregnancy complications and adverse birth outcomes are in part fueled by the rise in obesity and its associated co-morbidities in western societies. Fetal healthy development and placental function are disturbed by an obese, inflammatory environment associated with cytokines, such as interleukin-6, causing inadequate supply of nutrients to the fetus and perinatal programming with severe health consequences. Method of Study : Mice received high fat diet (HFD) before and during gestation to induce obesity. We performed an IL-6 receptor antibody (MR16-1) treatment in pregnant obese mice at embryonic days E0.5, E7.5 and E14.5 to investigate whether this could ameliorate HFD-induced and obesity-associated placental dysfunction, evaluated by stereology and western blot, and improve offspring outcome at E15.5 in obese dams. Results : We observed fewer fetuses below the 10th percentile and placental vascularization was less aggravated following MR16-1 treatment of obese dams, showing slight improvements in labyrinth zone (Lz) vascularization. However, placental dysfunction and fetal growth restriction were still apparent in MR16-1 dams compared to lean control dams. Molecular analysis showed significantly elevated IL-6 level in placentas of MR16-1 treated dams. Conclusion : Treatment with MR16-1 blocks IL-6 signaling in the placenta, but has only limited effects on preventing HFD-associated placental dysfunction and offspring outcomes in mice, suggesting further mechanisms in the deterioration of placental vascularization and fetal nutrient supply as a consequence of maternal obesity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kretschmer, TobiasUNSPECIFIEDorcid.org/0000-0002-4202-0806UNSPECIFIED
Turnwald, Eva-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janoschek, RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wohlfarth, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Handwerk, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doetsch, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hucklenbruch-Rother, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Appel, SarahUNSPECIFIEDorcid.org/0000-0003-0315-6513UNSPECIFIED
URN: urn:nbn:de:hbz:38-669704
DOI: 10.1111/aji.13564
Journal or Publication Title: Am. J. Reprod. Immunol.
Volume: 88
Number: 1
Date: 2022
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1600-0897
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INTERLEUKIN-6 RECEPTOR; MATERNAL OBESITY; TOCILIZUMAB; INDUCTION; EXPRESSION; BLOCKADE; CELLS; WOMEN; GP130Multiple languages
Immunology; Reproductive BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/66970

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