title: Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres.
abstract: A map of human embryo development that combines imaging, molecular, genetic and epigenetic data for comparisons to other species and across pathologies would be greatly beneficial for basic science and clinical applications. Here, we compared mRNA and protein expression of key mediators of DNA methylation and histone modifications between mouse and human embryos, embryos from fertile/infertile couples, and following growth factor supplementation. We observed that individual mouse and human embryos are characterized by similarities and distinct differences in DNA methylation and histone modification patterns especially at the single-cell level. In particular, while mouse embryos first exhibited sub-compartmentalization of different histone modifications between blastomeres at the morula stage and cell sub-populations in blastocysts, differential histone modification expression was detected between blastomeres earlier in human embryos at the four- to eight-cell stage. Likewise, differences in epigenetic mediator expression were also observed between embryos from fertile and infertile couples, which were largely equalized in response to growth factor supplementation, suggesting that select growth factors might prevent alterations in epigenetic profiles during prolonged embryo culture. Finally, we determined that reduced expression via morpholino technologies of a single histone-modifying enzyme, Rps6ka4/Msk2, resulted in cleavage-stage arrest as assessed by time-lapse imaging and was associated with aneuploidy generation. Taken together, data document differences in epigenetic patterns between species with implications for fertility and suggest functional roles for individual epigenetic factors during pre-implantation development.
authors.affiliation: Center for Reproductive and Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology and Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Shawn L
authors.initials: SL
authors.lastname: Chavez
authors.affiliation: Center for Reproductive and Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology and Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Sohyun L
authors.initials: SL
authors.lastname: McElroy
authors.affiliation: Reproductive Medicine Center, University of Minnesota, Minneapolis, MN 55414, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bossert
authors.affiliation: Reproductive Medicine Center, University of Minnesota, Minneapolis, MN 55414, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: De Jonge
authors.affiliation: Center for Reproductive and Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology and Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA Iviomics, Valencia, Spain.
authors.forename: Maria Vera
authors.initials: MV
authors.lastname: Rodriguez
authors.affiliation: Center for Reproductive and Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology and Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Denise E
authors.initials: DE
authors.lastname: Leong
authors.affiliation: Department of Obstetrics and Gynecology and.
authors.forename: Barry
authors.initials: B
authors.lastname: Behr
authors.affiliation: Department of Obstetrics and Gynecology and.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Westphal
authors.affiliation: Center for Reproductive and Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology and Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA reneer@stanford.edu.
authors.forename: Renee A
authors.initials: RA
authors.lastname: Reijo Pera
mesh_terms: D000818:Animals; D001757:Blastomeres / Q000378:metabolism*; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008780:Methyltransferases / Q000235:genetics*; D051379:Mice; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
chemical_list: D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D008780:Methyltransferases; D038744:Ribosomal Protein S6 Kinases, 90-kDa