title: The model beetle Tribolium castaneum can be used as an early warning system for transgenerational epigenetic side effects caused by pharmaceuticals.
abstract: Pharmaceuticals are not currently tested for transgenerational and epigenetic side effects. The use of vertebrates as preclinical research models is limited by their long generation times, low numbers of progeny and ethical concerns. In contrast, invertebrates such as insects breed rapidly, produce many offspring and are more ethically acceptable, allowing them to be used for high-throughput screening. Here, we established Tribolium castaneum as a model to screen for the effect of drugs on complex fitness parameters and the expression of epigenetic regulatory genes. We tested diets supplemented with the psychoactive drug valproic acid (VPA), which is a histone deacetylase inhibitor, or the antioxidant curcumin, which is a histone acetyltransferase inhibitor. We found that VPA delayed development, reduced longevity, and increased female body weight compared to a control diet. Fertility and fecundity declined and the expression of epigenetic regulatory genes was induced in the untreated F1 generation. In contrast, curcumin did not affect development or body weight, but it increased longevity, caused a significant reduction in fertility, and induced the expression of epigenetic regulatory genes mostly in the treated F0 generation. VPA and curcumin administered to vertebrate models have similar effects to those we observed in T. castaneum, confirming that this beetle is potentially useful as an alternative model to screen for the epigenetic effect of drugs. T. castaneum also provides a valuable early warning system for transgenerational epigenetic risk factors that are difficult to detect in mammals.
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Department of Bioresources, Winchester Str. 2, 35394 Giessen, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Bingsohn
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Department of Bioresources, Winchester Str. 2, 35394 Giessen, Germany.
authors.forename: Eileen
authors.initials: E
authors.lastname: Knorr
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Department of Bioresources, Winchester Str. 2, 35394 Giessen, Germany; Institute for Insect Biotechnology, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. Electronic address: Andreas.Vilcinskas@agrar.uni-giessen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vilcinskas
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003474:Curcumin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D040941:Heredity; D059014:High-Throughput Nucleotide Sequencing; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000633:toxicity*; D007814:Larva / Q000187:drug effects / Q000235:genetics; D008136:Longevity / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009152:Mutagenicity Tests; D010641:Phenotype; D012098:Reproduction / Q000187:drug effects; D013997:Time Factors; D014231:Tribolium / Q000187:drug effects* / Q000235:genetics; D014635:Valproic Acid / Q000633:toxicity*
chemical_list: D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D051548:Histone Acetyltransferases; D003474:Curcumin
keywords: Curcumin; Drug development; Epigenetics; Insect models; Preclinical research; Tribolium castaneum; Valproic acid