title: Preconceptional paternal glycidamide exposure affects embryonic gene expression: single embryo gene expression study following in vitro fertilization.
abstract: Recognition of early determinants of disease onset has sparked an interest in paternally transmitted factors and their impact on the developing embryo. Acrylamide (AA), a widely distributed xenobiotic compound, is converted to its active metabolite glycidamide (GA) by the CYP2E1 enzyme. Based on its capacity to induce dominant lethal mutations, we hypothesized that paternal GA exposure would have a negative impact on embryonic genome activation, via GA-DNA and protamine adducts persisting in the fertilizing sperm. Using a combination of in vitro fertilization (IVF) techniques and RT-qPCR single embryo gene expression (SEGE), we studied the expression of key DNA repair genes and genes important for embryo development, at the 1-, 2-, 4- and 8-cell stage of the developing mouse embryo. Compared to controls paternal GA-exposure gave rise to an altered pattern of embryonic gene expression, with an initial reduced expression at early stages followed by increased expression at the 8-cell stage.
authors: Norwegian Institute of Public Health, Division of Environmental Medicine, Department of Chemical Toxicology, Nydalen, Oslo, Norway. asgeir.brevik@fhi.no
authors: Asgeir
authors: A
authors: Brevik
authors: Vendula
authors: V
authors: Rusnakova
authors: Nur
authors: N
authors: Duale
authors: Hege Holte
authors: HH
authors: Slagsvold
authors: Ann-Karin
authors: AK
authors: Olsen
authors: Ritsa
authors: R
authors: Storeng
authors: Mikael
authors: M
authors: Kubista
authors: Gunnar
authors: G
authors: Brunborg
authors: Birgitte
authors: B
authors: Lindeman
mesh_terms: D020106:Acrylamide / Q000378:metabolism; D000818:Animals; D018736:DNA Adducts / Q000032:analysis; D004260:DNA Repair / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism*; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D004852:Epoxy Compounds / Q000633:toxicity*; D005260:Female; D005307:Fertilization in Vitro; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D018812:Paternal Exposure / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013094:Spermatozoa / Q000737:chemistry
chemical_list: D018736:DNA Adducts; D004852:Epoxy Compounds; D009153:Mutagens; D020106:Acrylamide; C071834:glycidamide