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.


METHODS
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 factor(121). 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.


CONCLUSIONS
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.
Katz
Anna B
AB
Center for Molecular Fetal Therapy, Cincinnati Children's Hospital, Cincinnati, OH, USA.
Keswani
Sundeep G
SG
Habli
Mounira
M
Lim
Foong Y
FY
Zoltick
Philip W
PW
Midrio
Paola
P
Kozin
Elliot D
ED
Herlyn
Meenhard
M
Crombleholme
Timothy M
TM
D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010920:Placenta; D011247:Pregnancy
D036341:Intercellular Signaling Peptides and Proteins