Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells

• Published in: Communications biology 2020-05, Vol.3 (1), p.208-208, Article 208
• Main Authors: Seong, Ki-Hyeon, Ly, Nhung Hong, Katou, Yuki, Yokota, Naoko, Nakato, Ryuichiro, Murakami, Shinnosuke, Hirayama, Akiyoshi, Fukuda, Shinji, Kang, Siu, Soga, Tomoyoshi, Shirahige, Katsuhiko, Ishii, Shunsuke
• Format: Article
• Language: English
• Subjects: 13; 13/51; 14/19; 38/22; 38/77; 38/90; 38/91; 42; 45; 631/208/176; 631/208/729; 631/378; 631/443/319; 64; 64/24; Activating transcription factor 2; Amino acids; Biology; Biomedical and Life Sciences; Drosophila melanogaster; Environmental factors; Environmental stress; Epigenetics; Gene expression; Germ cells; Glycolysis; Heredity; Heterochromatin; Insects; Interleukin 6; Life Sciences; Metabolism; Metabolites; Offspring; Somatic cells; Tricarboxylic acid cycle
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-0935-z

Paternal environmental factors can epigenetically influence gene expressions in offspring. We demonstrate that restraint stress, an experimental model for strong psychological stress, to fathers affects the epigenome, transcriptome, and metabolome of offspring in a MEKK1-dATF2 pathway-dependent manner in Drosophila melanogaster . Genes involved in amino acid metabolism are upregulated by paternal restraint stress, while genes involved in glycolysis and the tricarboxylic acid (TCA) cycle are downregulated. The effects of paternal restraint stress are also confirmed by metabolome analysis. dATF-2 is highly expressed in testicular germ cells, and restraint stress also induces p38 activation in the testes. Restraint stress induces Unpaired 3 (Upd3), a Drosophila homolog of Interleukin 6 (IL-6). Moreover, paternal overexpression of upd3 in somatic cells disrupts heterochromatin in offspring but not in offspring from dATF-2 mutant fathers. These results indicate that paternal restraint stress affects metabolism in offspring via inheritance of dATF-2-dependent epigenetic changes. Ki-Hyeon Seong et al. report that paternal environmental stress affects the metabolism of their offspring in Drosophila melanogaster . They exposed male flies to stress by preventing them from moving for 10 hours at a time and then measured gene expression and metabolite levels in their offspring, who showed increased expression of amino acid and one-carbon metabolism-related genes and downregulation of glycolysis and the TCA cycle.