title: In ovo leptin administration inhibits chorioallantoic membrane angiogenesis in female chicken embryos through the STAT3-mediated vascular endothelial growth factor (VEGF) pathway.
abstract: Previous studies indicate that leptin regulates placental angiogenesis and fetal growth in mammals and that in ovo leptin administration affects embryonic development and hatch weight in the chicken. To test the hypothesis that leptin affects embryonic growth through modifying chorioallantoic membrane (CAM) angiogenesis, we injected 0.5 μg of recombinant murine leptin into the albumen of fertilized eggs before incubation. On embryonic day 12 (E12), the number and the total area of blood vessels on CAM were measured, and expression of genes involved in angiogenesis was quantitated to show the possible mechanisms. Leptin in ovo administration decreased (P < 0.05) both the total area of blood vessels and the number of small-sized capillaries on CAM of E12 female chicken embryos, which coincided with significantly decreased (P < 0.05) embryo weight on E12 and BW at hatching. Vascular endothelial growth factor (VEGF) and inducible and endothelial nitric oxide synthases (iNOS and eNOS) were all downregulated (P < 0.05) in CAM both at the mRNA and protein/activity levels with reduced (P < 0.05) nitric oxide (NO) concentration in chorioallantoic fluid of female embryos. Furthermore, signal transducer and activator of transcription-3 (STAT3) was found to be diminished (P < 0.05) both at the mRNA and protein levels and associated with decreased (P < 0.05) binding of STAT3 to VEGF promotor in the CAM of leptin-treated E12 female embryos. These data suggest that in ovo leptin administration affects CAM angiogenesis and embryo growth in female chicken embryos, probably through STAT3-mediated VEGF/NO pathways.
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: L
authors.initials: L
authors.lastname: Su
authors.forename: K
authors.initials: K
authors.lastname: Rao
authors.forename: F
authors.initials: F
authors.lastname: Guo
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: A A
authors.initials: AA
authors.lastname: Ahmed
authors.forename: Y
authors.initials: Y
authors.lastname: Ni
authors.forename: R
authors.initials: R
authors.lastname: Grossmann
authors.forename: R
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000187:drug effects*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase