A systems biology analysis of reproductive toxicity effects induced by multigenerational exposure to ionizing radiation in C. elegans

Ecotoxicology and Environmental Safety

Dag Anders Brede¹  Erica Maremonti¹  Catherine Lecomte-Pradines²  Rémi Guédon²  Olivier Armant²  Simon Galas³ 

[1] Centre for Environmental Radioactivity (CERAD), Faculty of Environmental Sciences and Natural Resource Management (MINA), Norwegian University of Life Sciences (NMBU), 1432 Ås, Norway;Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-ENV, SRTE, Laboratoire d'ECOtoxicologie des radionucléides (LECO), Cadarache, France;Institut des biomolecules Max Mousseron (IBMM), University of Montpellier, Centre National de Recherche Scientifique (CNRS), ENSCM, Montpellier, France;

关键词: Ionizing gamma radiation;    Multigenerational effects;    Caenorhabditis elegans;    Reproductive toxicity;    Spermatogenesis;    Germ cells;   

DOI  :  

来源: DOAJ

【 摘 要 】

Understanding the effects of chronic exposure to pollutants over generations is of primary importance for the protection of humans and the environment; however, to date, knowledge on the molecular mechanisms underlying multigenerational adverse effects is scarce. We employed a systems biology approach to analyze effects of chronic exposure to gamma radiation at molecular, tissue and individual levels in the nematode Caenorhabditis elegans. Our data show a decrease of 23% in the number of offspring on the first generation F0 and more than 40% in subsequent generations F1, F2 and F3. To unveil the impact on the germline, an in-depth analysis of reproductive processes involved in gametes formation was performed for all four generations. We measured a decrease in the number of mitotic germ cells accompanied by increased cell-cycle arrest in the distal part of the gonad. Further impact on the germline was manifested by decreased sperm quantity and quality. In order to obtain insight in the molecular mechanisms leading to decreased fecundity, gene expression was investigated via whole genome RNA sequencing. The transcriptomic analysis revealed modulation of transcription factors, as well as genes involved in stress response, unfolded protein response, lipid metabolism and reproduction. Furthermore, a drastic increase in the number of differentially expressed genes involved in defense response was measured in the last two generations, suggesting a cumulative stress effect of ionizing radiation exposure. Transcription factor binding site enrichment analysis and the use of transgenic strain identified daf-16/FOXO as a master regulator of genes differentially expressed in response to radiation. The presented data provide new knowledge with respect to the molecular mechanisms involved in reproductive toxic effects and accumulated stress resulting from multigenerational exposure to ionizing radiation.

【 授权许可】

Unknown