Disruption of the feto-maternal transfer zone via maternal obesity

• Applicant: Dr. Sarah Appel
• Subject Area: Gynaecology and Obstetrics
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 289593189

Obesity in women at reproductive age is increasing, and so is the number of pregnancies complicated by maternal obesity. Several studies revealed a connection between maternal obesity and the risk to develop a placental dysfunction, which in turn negatively affects fetal development. In this project we aim to study the hypothesis that maternal obesity induces a systemic inflammatory reaction which is mainly mediated by IL-6 and TNF-alpha, and which reduces the feto-maternal transfer capacity of the placenta and hence, fetal supply. Our data indicate that the obesity-induced inflammation alters endothelial cell homeostasis and destabilizes the intercellular connections between placental cells located within the feto-maternal transfer zone. In this grant we will determine the underlying molecular mechanisms of cytokine mediated placental damage and in our mouse model of maternal obesity we will analyse whether a nutritional intervention during pregnancy or a direct block of IL-6 and TNF-alpha may prevent vascular alterations and intercellular destabilisation in the feto-maternal transfer zone to improve fetal development. Our study will allow us to determine molecular targets for effective preventive and therapeutic strategies against placental dysfunction as a consequence of maternal obesity.

• DFG Programme: Research Grants