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Transcription and DNA methylation signatures of paternal care in hippocampal dentate gyrus of prairie voles (RRBS)

ABSTRACT: In socially monogamous prairie voles (Microtus ochrogaster), parental behaviors not only occur in mothers and fathers, but also can exist in virgin males. However, some virgin males display aggressive behaviors towards conspecific pups. Although this behavioral dichotomy in response to pup exposure has been well documented in male virgin voles, little is known about the gene expression changes underlie the parental behavioral differences and their regulatory mechanisms. To address this, we profiled the transcriptome and DNA methylome of hippocampal dentate gyrus of four prairie vole groups, attacker virgin males, parental virgin males, fathers, and mothers. We found a concordant pattern of gene transcription in parental virgin males and fathers, when comparing to the attacker group. The methylome analysis also revealed pathways with genes enriched for epigenetic changes involving both receptor-mediated and secondary messenger signaling across both behavioral phenotypes and sexual experiences. Furthermore, we found correlations between gene expression changes and DNA methylation differences between attacker and parental virgin males, which suggests a canonical gene expression regulatory role of DNA methylation in paternal care. Therefore, our study presents an integrated view of transcriptome and epigenome that provides a DNA epigenetic based molecular insight of paternal behavior.

ORGANISM(S): Microtus ochrogaster

PROVIDER: GSE214798 | GEO | 2023/07/12

REPOSITORIES: GEO

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Project description:The global prevalence of type 2 diabetes (T2D) is increasing, and it is contributing to the susceptibility to diabetes and its related epidemic in offspring. Although the impacts of paternal T2D on metabolism of offspring have been well established, the exact molecular and mechanistic basis that mediates these impacts remains largely unclear. Here we show that paternal T2D increases the susceptibility to diabetes in offspring through the gametic epigenetic alterations. Paternal T2D led to glucose intolerance and insulin resistance in offspring. Relative to controls, offspring of T2D fathers exhibited altered gene expression patterns in the pancreatic islets, with downregulation of several genes involved in glucose metabolism and insulin signaling pathway. Epigenomic profiling of offspring pancreatic islets revealed numerous changes in cytosine methylation depending on paternal T2D, including reproducible changes in methylation over several insulin signaling genes. Paternal T2D altered overall methylome patterns in sperm, with a large portion of differentially methylated genes overlapped with that of pancreatic islets in offspring. Our study revealed, for the first time, that T2D can be inherited transgenerationally through the mammalian germline by an epigenetic manner. For all comparisons shown, male F0 founders were weaned from mothers at 3 weeks of age, and sibling males were put into cages with high-fat diet (33% energy as fat) or control diet until 12 weeks of age, at which point mice fed with HFD were injected intraperitoneally with a low dose of STZ and kept on the same diet for 4 weeks. Fasting blood glucose was examined each week post-STZ for 4 weeks, and only glucose level at 7~11 mM was considered as type 2 diabetes. Females were always raised on standard diet. At 16 weeks, male F0 founders were mated with females. After 1 or 2 days, males were removed, and pregnant females were left alone until their litters were 3 weeks of age. Note that we always used virgin females to avoid confounding effects brought about by the females. At 3 weeks of age a portion of the offspring were sacrificed and islets were generated, each from an independent father.Samples from six control and six paternal type 2 diabetes offspring were chosen for microarray analysis.

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Transcription and DNA methylation signatures of paternal care in hippocampal dentate gyrus of prairie voles (RRBS)

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