Prepregnancy obesity and sFlt1-induced preeclampsia in mice: developmental programming model of metabolic syndrome.

Abstract

We sought to establish a model of fetal programming of metabolic syndrome by exposure to soluble fms-like tyrosine kinase-1 (sFlt1)-induced preeclampsia (PE) and preexisting maternal obesity (MO). CD-1 female mice were placed on either standard or high-fat diet for 3 months. On day 8 of pregnancy, mice were injected with either adenovirus-carrying sFlt1 or adenovirus-carrying murine immunoglobulin G2α Fc fragment. Offspring were studied at 6 months of age. Exposure to MO with/without PE resulted in significant increase in progeny's weight and adiposity. Blood pressure in males was significantly increased due to MO with PE. Metabolic blood analytes were affected in males and females exposed to only PE or MO with/without PE; inflammatory-in females exposed to MO with/without PE and males born to MO with PE; atherosclerotic-in females exposed to MO. Exposure to maternal prepregnancy obesity and sFlt1-induced preeclampsia alter the offspring's blood pressure, metabolic, inflammatory, and atherosclerotic profiles later in life.