# Integration of epigenetics into ecotoxicology: insights and fundamental research needs

**Authors:** Albano Pinto, Jana Asselman, Patrícia Pereira, Joana Luísa Pereira

PMC · DOI: 10.1111/brv.70105 · 2025-11-16

## TL;DR

This paper explores how epigenetics can improve understanding of environmental contaminant effects on organisms and highlights gaps in current knowledge.

## Contribution

The paper systematically reviews epigenetic modifications in ecotoxicological models and emphasizes the need for epigenetic-based biomarkers.

## Key findings

- Environmental contaminants can alter epigenetic marks like DNA methylation and histone modifications.
- There is a lack of fundamental knowledge about epigenetic regulation in ecotoxicological model species.
- Epigenetic-based biomarkers could enhance ecological risk assessment.

## Abstract

Epigenetics refers to heritable changes in genome function that occur without direct alterations to the DNA sequence. A multitude of environmental contaminants can influence the epigenetic marks of a genome. Changes of epigenetic marks including DNA methylation, histone modifications, and non‐coding RNAs can induce alterations at the gene transcription level, potentially leading to physiological long‐term changes that can be inherited transgenerationally. (Eco)Toxicoepigenetics is thus an emerging field of research focusing on linking environmental exposure with epigenome alterations, with a high postulated relevance for improved ecological risk assessment at the regulatory level. Despite its huge potential, fundamental knowledge is scarce and scattered concerning epigenetic regulation in relevant ecotoxicological model species and mechanisms of interaction between environmental contaminants and the epigenome. This is a paramount challenge for the efficient implementation of (eco)toxicoepigenetics that is not often recognised in the literature. Herein, we provide updated knowledge regarding the main epigenetic modifications that occur on ecotoxicologically relevant models and summarize the differences in epigenetic patterns between vertebrate and invertebrate species that are routinely used as test organisms in ecotoxicology. We also systematically revise what is known on the mechanisms through which environmental contaminants can modulate the epigenome, using three legacy contaminants of the aquatic compartment for which appreciable information exists concerning ecotoxicologically relevant species. Future directions for (eco)toxicoepigenetics research are discussed in the context of the existing knowledge, with particular emphasis on the much‐needed characterization of the epigenomes of ecotoxicological models and the need to understand better the mechanisms underlying the modulation of epigenetic marks and related machinery by environmental contaminants. This review will hopefully stimulate future research contributing to the continuous incorporation of epigenetic studies in ecotoxicology and the development and implementation of effective epigenetic‐based ecotoxicological biomarkers for environmental stress assessment.

## Full-text entities

- **Genes:** ALKBH1 (alkB homolog 1, histone H2A dioxygenase) [NCBI Gene 8846] {aka ABH, ABH1, ALKBH, alkB, hABH}, PRDM9 (PR/SET domain 9) [NCBI Gene 56979] {aka KMT8B, MEISETZ, MSBP3, PFM6, ZNF899}, H2BC21 (H2B clustered histone 21) [NCBI Gene 8349] {aka GL105, H2B, H2B-GL105, H2B.1, H2BE, H2BFQ}, DNMT3L (DNA methyltransferase 3 like) [NCBI Gene 29947], DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, H2AC18 (H2A clustered histone 18) [NCBI Gene 8337] {aka H2A, H2A.2, H2A/O, H2A/q, H2AFO, H2a-615}, TET3 (tet methylcytosine dioxygenase 3) [NCBI Gene 200424] {aka BEFAHRS, hCG_40738}, TRDMT1 (tRNA aspartic acid methyltransferase 1) [NCBI Gene 1787] {aka DMNT2, DNMT2, MHSAIIP, PUMET, RNMT1}, KAT8 (lysine acetyltransferase 8) [NCBI Gene 84148] {aka LIGOWS, MOF, MYST1, ZC2HC8, hMOF}, HEMK2 (HemK methyltransferase 2, ETF1 glutamine and histone H4 lysine) [NCBI Gene 29104] {aka C21orf127, KMT9, MTQ2, N6AMT, N6AMT1, PRED28}, Dnmt3a (DNA methyltransferase 3A) [NCBI Gene 13435] {aka MmuIIIA}, H4C2 (H4 clustered histone 2) [NCBI Gene 8366] {aka H4/I, H4FI, HIST1H4B}, CHPT1 (choline phosphotransferase 1) [NCBI Gene 56994] {aka CPT, CPT1}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, TET1 (tet methylcytosine dioxygenase 1) [NCBI Gene 80312] {aka CXXC6, LCX, bA119F7.1}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, DNMT3B (DNA methyltransferase 3 beta) [NCBI Gene 1789] {aka FSHD4, ICF, ICF1, M.HsaIIIB}, TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 54790] {aka IMD75, KIAA1546, MDS}, SUV39H1 (SUV39H1 histone lysine methyltransferase) [NCBI Gene 6839] {aka H3-K9-HMTase 1, KMT1A, MG44, SUV39H}, Dnmt3b (DNA methyltransferase 3B) [NCBI Gene 13436] {aka MmuIIIB}, TDG (thymine DNA glycosylase) [NCBI Gene 6996] {aka hTDG}, CPA1 (carboxypeptidase A1) [NCBI Gene 1357] {aka CPA}, ERAL1 (Era like 12S mitochondrial rRNA chaperone 1) [NCBI Gene 26284] {aka CEGA, ERA, ERA-W, ERAL1A, ERAL1B, H-ERA}
- **Diseases:** neurodevelopmental impairment (MESH:D009422), MECHANISMS (MESH:D041781), NMAD-1 (MESH:C538557), toxicity (MESH:D064420), neurological disease (MESH:D020271), neurological disorders (MESH:D009461), DYNAMIC (MESH:D000092242), neurodegeneration (MESH:D019636), cancer (MESH:D009369)
- **Chemicals:** N6-methyladenine (MESH:C005955), Reduced glutathione (MESH:D005978), Cd (MESH:D002104), Arsenic (MESH:D001151), 5-hmC (MESH:C011865), 6-mA (-), 5-formylcytosine (MESH:C560973), Sodium-arsenite (MESH:C017947), 5-carboxylcytosine (MESH:C560974), homocysteine (MESH:D006710), Cr (MESH:D002857), S-adenosylmethionine (MESH:D012436), 5-mC (MESH:D044503), Cytosine (MESH:D003596), Water (MESH:D014867), adenine (MESH:D000225), methionine (MESH:D008715), carbon (MESH:D002244), arsenic trioxide (MESH:D000077237)
- **Species:** Xenopus laevis (African clawed frog, species) [taxon 8355], Ascidiacea (sea squirts, class) [taxon 7713], Magallana gigas (Pacific oyster, species) [taxon 29159], Drosophila melanogaster (fruit fly, species) [taxon 7227], Romanomermis culicivorax (species) [taxon 13658], Apis mellifera (bee, species) [taxon 7460], Diptera (flies, order) [taxon 7147], Lumbricus terrestris (common earthworm, species) [taxon 6398], Procambarus fallax (deceitful crayfish, species) [taxon 215716], Danio rerio (leopard danio, species) [taxon 7955], Oreochromis niloticus (Nile tilapia, species) [taxon 8128], Homo sapiens (human, species) [taxon 9606], Anguilla anguilla (European eel, species) [taxon 7936], Asteroidea (sea stars, class) [taxon 7588], Paracentrotus lividus (common sea urchin, species) [taxon 7656], Nippostrongylus brasiliensis (species) [taxon 27835], Daphnia magna (species) [taxon 35525], Hydra vulgaris (swiftwater hydra, species) [taxon 6087], C. elegans [taxon 328850], Ciona intestinalis (sea vase, species) [taxon 7719], Daphnia sp. (species) [taxon 35529], Sus scrofa domesticus (domestic pig, subspecies) [taxon 9825], Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239]
- **Mutations:** cytosine-C5, serine/arginine
- **Cell lines:** HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965860/full.md

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Source: https://tomesphere.com/paper/PMC12965860