Antioxidant responses and deregulation of epigenetic writers and erasers link oxidative stress and DNA methylation in bovine blastocysts

Early mammalian embryos derived from in vitro fertilization are exposed to conditions distinct from the native oviduct‐uterine environment, including atmospheric oxygen that promotes cellular oxidative stress and alters gene expression. High oxygen partial pressure during embryo development is assoc...

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Bibliographic Details
Published in:Molecular reproduction and development 2017-12, Vol.84 (12), p.1296-1305
Main Authors: Bomfim, Monalisa M., Andrade, Gabriella M., del Collado, Maite, Sangalli, Juliano R., Fontes, Patrícia K., Nogueira, Marcelo F.G., Meirelles, Flávio V., da Silveira, Juliano C., Perecin, Felipe
Format: Article
Language:English
Subjects:
Animals
Antioxidants
Antioxidants - metabolism
Apoptosis
Blastocyst - cytology
Blastocyst - metabolism
Blastocysts
Cattle
Cell culture
cellular stress
Deoxyribonucleic acid
Deregulation
DNA
DNA Methylation
embryo development
Embryogenesis
Embryos
Epigenesis, Genetic
epigenetic
Epigenetics
Gene expression
Gene Expression Regulation, Developmental
HDAC2 protein
Histone deacetylase
In vitro fertilization
microRNA
Oviduct
Oxidative Stress
Pregnancy
Pressure
Reactive oxygen species
Superoxide dismutase
Uterus
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Summary:Early mammalian embryos derived from in vitro fertilization are exposed to conditions distinct from the native oviduct‐uterine environment, including atmospheric oxygen that promotes cellular oxidative stress and alters gene expression. High oxygen partial pressure during embryo development is associated with low pregnancy rates and increased embryonic apoptosis. We investigated how bovine embryos responded to high (20%) or low (5%) oxygen partial pressure during in vitro culture, evaluating levels of reactive oxygen species (ROS) as well as changes in the expression of oxidative stress‐ and epigenetic‐related transcripts and miRNAs in blastocysts. Additionally, we determined the global DNA methylation levels in the resulting embryos. Our data indicated that bovine blastocysts produced in vitro under high oxygen partial pressure possessed elevated ROS abundance and exhibited increased expression of CAT, GLRX2, KEAP1, NFR2, PRDX1, PRDX3, SOD1, TXN, and TXNRD1, versus reduced levels of the oxidative stress‐related bta‐miR‐210. These stressed embryos also presented altered expression of the epigenetic‐associated transcripts DNMT3A, H2AFZ, H3F3B, HDAC2, MORF4L2, REST, and PAF1. In addition, we demonstrated that embryos cultured under high oxygen partial pressure have increased global DNA methylation, suggesting that DNA hypermethylation is mediated by the deregulation of epigenetic‐related enzymes due to oxidative stress.
ISSN:1040-452X
1098-2795
DOI:10.1002/mrd.22929