Project description:To investigate the impact of A20 on testosterone synthesis in the context of age-related inflammation, we employed lentiviral constructs to establish TNFAIP3-overexpressing TM3 cell lines. Subsequently, we conducted gene expression profiling analysis using RNA-seq data obtained from both normal TM3 cells and TNFAIP3-overexpressing TM3 cells.
Project description:Obesogens such as tributyltin (TBT) are xenobiotic compounds that promote obesity, in part by distorting the normal balance of lipid metabolism. The obesogenic effects of TBT can be observed in directly exposed (F1 and F2 generations) and also subsequent generations (F3 and beyond) that were never exposed. To address the effects of TBT exposure on germ cells, we exposed pregnant transgenic OG2 mouse dams (F0), which specifically express EGFP in germline cells, to an environmentally relevant dose of TBT throughout gestation through drinking water. When fed with a high fat diet (HFD), F3 male offspring of TBT-exposed F0 dams (TBT-F3) accumulated much more body fat than did Control-F3 males. TBT-F3 males also lost more body fluid and lean compositions than did Control-F3 males. Expression of genes involved in transcriptional regulation or mesenchymal differ-entiation was upregulated in somatic cells of TBT-F1 (but not TBT-F3) E18.5 fetal testes, and promoter-associated CpG islands were hyper-methylated in TBT-F1 somatic cells. Global mRNA expression of protein-coding genes in F1 or F3 fetal testicular cells was unaffected by F0 exposure to TBT; however, expression of a subset of endogenous retroviruses was significantly affected in F1 and F3. We infer that TBT may directly target testicular somatic cells in F1 testes to irreversibly affect epigenetic suppression of endogenous retroviruses in both germline and somatic cells.