Unknown,Transcriptomics,Genomics,Proteomics

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Effects of GDM involves alterations in gene specific DNA methylation

ABSTRACT: Gestational diabetes mellitus(GDM) will bring health issues for offspring. The offspring of diabetic mothers often reveal high birth weight and are prone to have obesity, hypertension and dyslipidemia. It was implied that the phenotype of offspring might be influenced by intrauterine environment and planned in utero already in addition to the genetic influences.M-bM-^@M-^XProgrammingM-bM-^@M-^Y refers to the process whereby a stimulus at a critical window of development has long-term effects. A large body of studies investigated the adverse intrauterine environment was correlated with poor fetal growth and increased risk of Type 2 diabetes in the adulthood. Epigenetic mechanism has been proposed to involve in the link between environmental and nutritional factors and gene expression regulation. DNA methylation is one of the major epigenetic modifications. We hypothesized that DNA methylation changes could participate in the gene expression related to glucose intolerance in the offspring. Furthermore, DNA methylation might also determine the transgenerational disease transmission. comparison of intrauterine hyperglycemia exposed rats vs. control rats for genome-wide DNA methylation changes

ORGANISM(S): Rattus norvegicus

SUBMITTER: Huixia Yang

PROVIDER: E-GEOD-65779 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Parental exposure to environmental stress can result in an increased diseases risk in the offspring. Although literature on maternal contribution to hereditary diseases are growing, the paternal contribution is frequently underrecognized. Since human studies reported that 80% of transmitted mutations arise in the paternal germline, it is crucial to understand the mechanism underlying the paternally inherited genome instability. Ionizing radiation (IR) is a major source of mutagenesis through inducing DNA double-strand breaks (DSBs). Here, we used sex-separated C. elegans mutants to investigate the paternal contribution to IR-induced transgenerational effects. Specifically, we found that paternal exposure to IR leads to a transgenerational embryonic lethality, and this effect is only observed when the radiation exposure occurred close to the time of fertilization. In the offspring of the irradiated males (F1 generation), we detected various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement, and aneuploidy. These phenotypes are attributed to the usage of two error-prone repair machinery, the polymerase-theta mediated end joining (TMEJ) and the non-homologous End Joining (NHEJ). Surprisingly, depletion of a human histone H1.0 ortholog, HIS-24, can significantly rescue this transgenerational embryonic lethality. Moreover, this rescue effect is associated with the downregulation of heterochromatin marker histone 3 lysine 9 di-methylation (H3K9me2), and the knocking-down of heterochromatin protein, HPL-1, could mimic the rescue effect of HIS-24 depletion. We also noticed that removal of the histone H1 and heterochromatin marker could activate the error-free repair machinery, Homologous Recombination repair (HR), thus improving the viability of the offspring carrying paternally inherited DNA damage. Altogether, our work sheds light on the importance of paternal radiation exposure on the health of offspring. In addition, our work establishes a previously unknown mechanism underlying the transgenerational genome instability and provides a potential therapeutic target for preventing the hereditary diseases caused by paternal radiation exposure.

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Effects of GDM involves alterations in gene specific DNA methylation

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