Involvement of insulin-like growth factor 2 in angiogenic factor transcription in Bi-maternal mouse conceptuses

Imprinted genes in which only one of the two parental chromosome copies is expressed have a substantial effect on mammalian ontogenesis. On mouse distal chromosome 7, the paternally expressed gene insulin-like growth factor 2 (Igf2) is separated by approximate 100 kb from the maternally expressed non-coding gene H19. However, there is limited knowledge of the manner in which Igf2 transcription affects the other genes involved in embryonic development. To clarify this, we performed quantitative gene expression analysis for representative angiogenic factors-Vegf, Flt1, Flt4, Flk1, Ang1, Ang2, Tie1, and Tie2-for 3 types of bi-maternal conceptuses containing genomes with non-growing (ng) and fully grown (fg) oocytes. The genetic backgrounds of the ng oocytes were 1) the wild type (ng(wt)), 2) mutant mice carrying a 3-kb deletion of the H19 transcription unit (ng(H19Delta3-KO)/fg) and 3) mutant mice carrying a 13-kb deletion in the H19 transcription unit, including the germline-derived differentially methylated region on chromosome 7 (ng(H19Delta13-KO)/fg). In the ng(wt)/fg and ng(H19Delta3-KO)/fg placentae, Vegf and Flt1 were upregulated compared with the mean value for the wt placenta, whereas in the ng(H19Delta13-KO)/fg placenta, these transcriptional levels were restored. In the fetus, however, only 2 genes among the 8 genes analyzed were significantly changed in the bi-maternal fetuses, indicating that the effects of the Igf2 mRNA level on angiogenic factor transcription in the fetus differed from those in the placenta. Our results indicated that the Igf2 mRNA level affects transcription of angiogenic factors in both bi-maternal placentae and fetuses.