Aberrant expression of imprinted genes in post-implantation XXXX embryos.

@entity35 @entity2620 @entity2085 @entity440
AIM: Imprinted genes are known regulators of embryo growth. Studies from our laboratory have demonstrated that treatment of adult male @entity35 with @entity440 increased post-implantation loss at around midgestation. Expression of @entity2620 ( @entity2620 ), a paternally expressed imprinted gene was down-regulated in the resorbing embryos obtained at embryonic day 13. Hypomethylation of @entity2620 -H19 imprint control region was observed in the resorbing embryo sires and spermatozoa obtained from @entity440 -treated @entity35 thereby suggesting that errors in imprint acquisition during spermatogenesis can result in @entity2085 . The present study aims at studying the expression of other imprinted genes, besides @entity2620 in the embryos sired by @entity440 -treated males. MAIN METHODS: Gene expression profiles of resorbing versus normal embryos were assessed by microarrays. Real time quantitative RT-PCR for six imprinted genes and four genes involved in cell cycle was done to validate gene expression data. The affected pathways and functions were identified in the resorbing embryos and effect on cell cycle was confirmed by flow cytometry. KEY FINDINGS: Aberrant expression of a number of imprinted genes was observed in the resorbing embryos when compared to the normal embryos at embryonic days 11 and 13. Down-regulation of Notch signaling, Wnt signaling and cell cycle pathway was observed in the resorbing embryos. SIGNIFICANCE: The study suggests that exposure of male germ cells to @entity440 during adulthood results in aberrant expression of imprinted genes and down-regulation of development associated pathways in the F(1) progeny thereby causing @entity2085 .
