Targeted placental delivery of insulin-like growth factor-II increases fetal weight in P0 mice

s / Placenta 36 (2015) A1eA60 A6 lactogen signalling, and their brains processed for microarray analysis and immunohistochemistry. Results: Maternal behaviour was significantly altered. We identified a deficit in the dam’s ability to retrieve pups and build a nest dependent of the genotype of the pups. Importantly, there were also marked differences in anxiety like behaviour across the cohorts. Microarray analysis demonstrated significant alterations in gene expression in the maternal brain, which preceded the aberrant maternal behaviours whilst BrdU Immunohistochemistry revealed variations in cell proliferation across the cohorts. Conclusion: This work directly demonstrates a link between placental signalling and the induction of maternal behaviour during pregnancy regulated by an imprinted gene. Additionally, it may have translational relevance as Phlda2 has been identified as aberrantly expressed in 25% of pregnancies blighted by fetal growth restriction potentially explaining the association between low birth weight and prenatal depression. NI2.6. TARGETED PLACENTAL DELIVERY OF INSULIN-LIKE GROWTH FACTOR-II INCREASES FETAL WEIGHT IN P0 MICE Anna King , John Aplin , Nicola Tirelli , Lynda Harris . Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester, UK; Manchester Pharmacy School, The University of Manchester, Manchester, UK Objectives: Insulin-like growth factor-II (IGF-II) enhances placental function and improves fetal viability in animal models of fetal growth restriction (FGR); however, as the IGF-1 receptor is expressed ubiquitously, IGF-II cannot be safely administered to humans as a treatment for FGR. We have previously shown that targeted delivery of IGF-II to the placenta of wild type mice, using liposomes decorated with the placental homing peptide iRGD, significantly increased placental weight. Here we examine the outcome of targeted placental delivery of IGF-II in the placental-specific Igf2 knockout (P0) mouse, a well characterised model of FGR. Methods: Liposomes were prepared by the thin film extrusion method from the natural phospholipid distearoyl-phosphatidylcholine (DSPC; 32.5mM), cholesterol (15mM), polyethylene glycol (PEG; 1.875mM) and PEG-maleimide (0.625mM). The iRGD homing peptide (1.25mmol) was covalently attached to 25% of surface lipids and IGF-II (13mM) was encapsulated. Vehicle control (PBS), IGF-II (1mg/kg) or iRGD liposomes containing IGF-II (0.3mg/kg) were administered intravenously to P0 mice on embryonic (E) day 11.5, 13.5, 15.5 and 17.5 (N1⁄48/group). Animals were sacrificed on E18.5 and fetal and placental weights were collected. Results: Targeted administration of IGF-II significantly increased fetal weight (*P