Addition of insulin during oocyte maturation impacts the epigenome of Day 8 bovine blastocysts

• Metabolic disorders such as obesity or diabetes are associated with impaired fertility and changes in insulin signaling. Bovine in vitro oocyte maturation is a good model to study the impact of metabolic imbalance on subsequent embryonic development. Effects of elevated insulin during oocyte maturation on the epigenome of Day 8 bovine blastocyst (BC8) were investigated. Oocytes (n=882) were in vitro matured with two different insulin concentrations, INS10 (10μg/ml) and INS0.1 (0.1 μg/ml) or as control, INS0. Pools of BC8 were used for gDNA extraction and epigenome data of DNA-methylation were obtained from an EDMA oligo-array (EmbryoGENE). A bioinformatics pipeline was developed to analyze the differentially methylated regions (DMR) when compared to controls by quantification of methylation measurements based on M values, former described by Shojaei Saadi et al., 2014. The analysis showed that 7632 and 3914 regions were hypo-methylated in the INS0.1 and INS10 groups versus INS0 whereas 6026 and 8504 regions were hyper-methylated in INS0.1 and INS10 groups versus INS0. Further investigation of the localization of DMR in genes showed that the conservation odds (methylation) were in general higher in coding regions and CpG islands compared with noncoding regions. We observed a large overlap of DMRs in the insulin groups (3233 common DMRs). These numerous changes illustrate that insulin added during the preconception period alters the methylation pattern of the early embryo. More investigations about gene groups/pathways corresponding to highly DMR will be performed and compared with the gene expression data obtained from the same samples. These findings confirm the wide range of changes induced by insulin on gene expression of Day 8 embryos [Laskowski et al., http://dx.doi.org/10.1071/RD15315] and contribute to a better understanding of mechanisms by which metabolic disorders can affect embryonic development and subsequent health of the offspring.

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LANTBRUKSVETENSKAPER  -- Bioteknologi med applikationer på växter och djur -- Genetik och förädling inom lantbruksvetenskap (hsv//swe)

AGRICULTURAL SCIENCES  -- Agricultural Biotechnology -- Genetics and Breeding in Agricultural Sciences (hsv//eng)

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