DNA epigenetic marks are linked to embryo aberrations in amphipods

Elena Gorokhova,Natalia Y Tretyakova,Nisha H Motwani,Brita Sundelin,Giulia Martella,Hitesh V Motwani

doi:10.1038/s41598-020-57465-1

Abstract

Linking exposure to environmental stress factors with diseases is crucial for proposing preventive and regulatory actions. Upon exposure to anthropogenic chemicals, covalent modifications on the genome can drive developmental and reproductive disorders in wild populations, with subsequent effects on the population persistence. Hence, screening of chemical modifications on DNA can be used to provide information on the probability of such disorders in populations of concern. Using a high-resolution mass spectrometry methodology, we identified DNA nucleoside adducts in gravid females of the Baltic amphipods Monoporeia affinis, and linked the adduct profiles to the frequency of embryo malformations in the broods. Twenty-three putative nucleoside adducts were detected in the females and their embryos, and eight modifications were structurally identified using high-resolution accurate mass data. To identify which adducts were significantly associated with embryo malformations, partial least squares regression (PLSR) modelling was applied. The PLSR model yielded three adducts as the key predictors: methylation at two different positions of the DNA (5-methyl-2′-deoxycytidine and N6-methyl-2′-deoxyadenosine) representing epigenetic marks, and a structurally unidentified nucleoside adduct. These adducts predicted the elevated frequency of the malformations with a high classification accuracy (84%). To the best of our knowledge, this is the first application of DNA adductomics for identification of contaminant-induced malformations in field-collected animals. The method can be adapted for a broad range of species and evolve as a new omics tool in environmental health assessment.

Highlights

Linking exposure to environmental stress factors with diseases is crucial for proposing preventive and regulatory actions
The evidence is accumulating that environmental chemicals that exhibit reproductive toxicity do so, at least in part, through genotoxic mechanisms and epigenetic alterations www.nature.com/scientificreports in genomic DNA10,30
Using an untargeted adductomics approach with High-resolution mass spectrometry (HRMS), we found that the frequency of embryo aberrations in Baltic Sea amphipods is related to the levels of certain Deoxyribonucleic acid (DNA) modifications in females and their embryos

Summary

Introduction

Linking exposure to environmental stress factors with diseases is crucial for proposing preventive and regulatory actions. The PLSR model yielded three adducts as the key predictors: methylation at two different positions of the DNA (5-methyl-2′-deoxycytidine and N6methyl-2′-deoxyadenosine) representing epigenetic marks, and a structurally unidentified nucleoside adduct These adducts predicted the elevated frequency of the malformations with a high classification accuracy (84%). Covalent DNA adducts can be formed by chemicals that are electrophilic or form reactive metabolites[1,2,3] Another pathway for modification of the DNA is through oxidation by reactive oxygen species (ROS) formed under oxidative stress[4,5]. Physical adsorption causes hydrophobic contaminants to become highly enriched in sediments and porewater as compared to the water column[16] This makes the benthic animals, such as amphipods, polychaetes, and clams, vulnerable to continuous exposure to the sediment-bound compounds. Such organisms are useful as sentinels in environmental monitoring programs

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Results

Conclusion