Placental gene transfer: transgene screening in mice for trophic effects on the placenta

Objective: We hypothesized that gene transfer of select growth factors to the placenta may enhance placental and fetal growth. Thus, we examined the effect of 8 growth factor transgenes on murine placenta. Study Design: Adenoviral-mediated site-specific intraplacental gene transfer of 8 different growth factor transgenes at embryonic day (e) 14 was performed. Transgenes included angiopoietin-1, angiopoietin-2 (Ang-2), basic fibroblast growth factor, hepatocyte growth factor, insulin-like growth factor-1 (IGF-1), placenta growth hormone, platelet-derived growth factor-B (PDGF-B), and vascular endothelial growth factor121. Fetuses and placentas were harvested at e17 and assessed for survival, gene transfer efficiency, placenta area, and fetal and placental weights. Results: Efficient gene transfer to the placenta was detected with minimal dissemination to the fetus. Overexpression of IGF-1, PDGF-B, and Ang-2 resulted in an increase in placenta cross-sectional area. Only Ang-2 gene transfer resulted in increased fetal weight, and only Ang-2 and basic fibroblast growth factor resulted in a change in placental weight. Conclusion: Site-specific placental gene transfer results in efficient gene transfer with minimal dissemination to the fetus. Adenoviral-mediated IGF-1, adenoviral-mediated PDGF-B, and adenoviral-mediated Ang-2 significantly increase placenta growth. © 2009 Mosby, Inc. All rights reserved.