Male-transmitted transgenerational effects of the herbicide linuron on DNA methylation profiles in Xenopus tropicalis brain and testis

The Science of The Total Environment, Год журнала: 2024, Номер 923, С. 170949 - 170949

Опубликована: Фев. 15, 2024

The herbicide linuron can cause endocrine disrupting effects in Xenopus tropicalis frogs, including offspring that were never exposed to the contaminant. mechanisms by which these are transmitted across generations need be further investigated. Here, we examined transgenerational alterations of brain and testis DNA methylation profiles paternally inherited from grandfathers developmentally an environmentally relevant concentration linuron. Reduced representation bisulfite sequencing (RRBS) revealed numerous differentially methylated regions (DMRs) (3060 DMRs) (2551 adult male F2 generation. Key genes involved somatotropic (igfbp4) thyrotropic signaling (dio1 tg) correlated with phenotypical body size, weight, hind limb length plasma glucose levels, indicating changes could potential mediators Testis DMRs found essential for spermatogenesis, meiosis germ cell development (piwil1, spo11 tdrd9) their levels number cells nests per seminiferous tubule, endpoint disrupted spermatogenesis. also identified several central machinery regulates epigenetic landscape (dnmt3a mbd2) histone acetylation (hdac8, ep300, elp3, kat5 kat14), may at least partly drive linuron-induced effects. results this genome-wide profiling contribute better understanding inheritance amphibians.

Язык: Английский

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Risk policy tools for high-risk industrial sites in Normandy (France) and Piedmont (Italy): more hazards-focused than vulnerabilities-focused

Journal of Risk Research, Год журнала: 2025, Номер unknown, С. 1 - 27

Опубликована: Апрель 21, 2025

Язык: Английский

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Advancing translational exposomics: bridging genome, exposome and personalized medicine

Human Genomics, Год журнала: 2025, Номер 19(1)

Опубликована: Апрель 30, 2025

Understanding the interplay between genetic predisposition and environmental lifestyle exposures is essential for advancing precision medicine public health. The exposome, defined as sum of all an individual encounters throughout their lifetime, complements genomic data by elucidating how external internal exposure factors influence health outcomes. This treatise highlights emerging discipline translational exposomics that integrates genomics, offering a comprehensive approach to decipher complex relationships exposures, variability, disease phenotypes. We highlight cutting-edge methodologies, including multi-omics technologies, exposome-wide association studies (EWAS), physiology-based biokinetic modeling, advanced bioinformatics approaches. These tools enable precise characterization both facilitating identification biomarkers, exposure-response relationships, prediction mechanisms. also consider importance addressing socio-economic, demographic, gender disparities in research. emphasize exposome can contextualize variation enhance causal inference, especially vulnerable populations diseases. By showcasing concrete examples proposing integrative platforms exposomics, this work underscores critical need bridge genomics prevention, risk stratification, decision-making. offers new paradigm understanding beyond genetics alone.

Язык: Английский

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Altered gut microbiota community structure and correlated immune system changes in dibutyl phthalate exposed mice

Ecotoxicology and Environmental Safety, Год журнала: 2023, Номер 262, С. 115321 - 115321

Опубликована: Авг. 5, 2023

Di-n-butyl phthalate (DBP) is a ubiquitous environmental contaminant linked with various adverse health effects, including immune system dysfunction. Gut microbial dysbiosis can contribute to wide range of pathogenesis, particularly disease. Here, we investigated the impact DBP on gut microbiome and examined correlations changes after five weeks oral exposure (10 or 100 mg/kg/day) in adult male mice. The fecal composition was characterized using 16S rRNA sequencing. DBP-treated mice displayed significantly distinct community composition, indicated by Bray-Curtis distance. Numerous amplicon sequence variants (ASVs) at genus level were altered. Compared vehicle control group, 10 mg/kg/day group had 63 more abundant 65 less ASVs, while 60 ASVs increased 76 decreased group. Both treatment groups showed higher abundances assigned Desulfovibrio (Proteobacteria phylum) Enterorhabdus genera, belonging Parabacteroides, Lachnospiraceae UCG-006 Lachnoclostridium common compared Interestingly, an ASV Rumniniclostridium 6, which mice, demonstrated negative correlation number non-classical monocytes observed blood animals. In addition, from UCG-001, animals, positive monocyte increase. This study shows that greatly modifies bacterial indicates potential contribution DBP-induced impairment, illustrating importance investigating how interactions between exposome components affect health.

Язык: Английский

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Scientometric review: Concentration and toxicity assessment in environmental non-targeted LC/HRMS analysis

Trends in Environmental Analytical Chemistry, Год журнала: 2023, Номер 40, С. e00217 - e00217

Опубликована: Окт. 13, 2023

Non-targeted screening with LC/HRMS is a go-to approach to discover relevant contaminants in environmental water samples that contain an abundance of chemicals. The rapidly increasing popularity non-targeted has initiated development diverse set methods for assessing the concentration and toxicity detected This review aims benchmark trends NTS literature particular focus on (1) used quantification tentatively identified chemicals lack analytical standards, (2) chemicals, (3) combining former into risk evaluation. Here we provide scientometric these strategies based Web Science referenced papers published between 2019 2022. General show assessments are widely employed NTS, reaching 66% 45% over four years, respectively. Simultaneously, only 13% covered here combine results factor or similar. With this aim highlight advantages gaps approaches assessment guidelines more homogeneous data interrogation extrapolation.

Язык: Английский

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Breast cancer risk and prevention in 2024: An overview from the Breast Cancer UK ‐ Breast Cancer Prevention Conference

Cancer Medicine, Год журнала: 2024, Номер 13(18)

Опубликована: Сен. 1, 2024

Abstract The Breast Cancer UK—Breast Prevention Conference addressed risk from environmental pollutants and health behaviour‐related breast‐cancer risk. Epidemiological studies examining individual chemicals breast cancer have produced inconclusive results including endocrine disrupting (EDCs) Bisphenol A, per‐ polyfluorinated alkyl substances as well aluminium. However, laboratory shown that multiple EDCs, can work together to exhibit effects, even when combined at levels alone are ineffective. TEXB‐α/β assay measures total estrogenic load, provided evidence of a link between multiple‐chemical exposures cancer. prospective using needed establish causative link. There is also need assess real‐life exposure environmental‐chemical mixtures during pregnancy, their potential involvement in programming adverse foetal outcomes later life. Higher rates occurred alongside increases potentially‐modifiable factors such obesity. Increasing body‐mass index associated with increased developing postmenopausal cancer, but decreased premenopausal In contrast, lower Asian compared Western populations been linked soya/isoflavone consumption. Risk by breastfeeding, which addition the decrease observed for each birth young first‐birth. those higher self‐reported physical activity. Current suggests survivors should avoid weight gain, be physically active, eat healthy diet overall health. A broad scientific perspective on requires focus both Research into chemical needs epidemiological order test effects Behaviour‐related research implementation deeper understanding mechanisms prevention.

Язык: Английский

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Automated Image-Based Fluorescence Screening of Mitochondrial Membrane Potential in Daphnia magna: An Advanced Ecotoxicological Testing Tool

Environmental Science & Technology, Год журнала: 2024, Номер 58(36), С. 15926 - 15937

Опубликована: Авг. 27, 2024

This study demonstrated the strengths of in vivo molecular staining coupled with automated imaging analysis

Язык: Английский

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Perfluorooctanesulfonic acid (PFOS) induced cancer related DNA methylation alterations in human breast cells: A whole genome methylome study

The Science of The Total Environment, Год журнала: 2024, Номер 949, С. 174864 - 174864

Опубликована: Июль 20, 2024

DNA methylation plays a pivotal role in cancer. The ubiquitous contaminant perfluorooctanesulfonic acid (PFOS) has been epidemiologically associated with breast cancer, and can induce proliferation malignant transformation of normal human epithelial cells (MCF-10A), but the information about its effect on is sparse. aim this study was to characterize whole-genome methylome effects PFOS our cell model compare findings previously demonstrated alterations tumor tissues. profile assessed at single CpG resolution MCF-10A treated 1 μM for 72 h by using Enzymatic Methyl sequencing (EM-seq). We found 12,591 differentially methylated CpG-sites 13,360 100 bp tiles exposed cells. These regions (DMRs) overlapped 2406 genes which 494 were long non-coding RNA 1841 protein coding genes. identified 339 affected that have shown display altered cancer tissue several other related development. This includes hypermethylation GACAT3, DELEC1, CASC2, LCIIAR, MUC16, SYNE1 hypomethylation TTN KMT2C. DMRs also estrogen receptor (ESR1, ESR2, ESRRG, ESRRB, GREB1) responsive (GPER1, EEIG1, RERG). gene ontology analysis revealed pathways phenotypes such as adhesion growth. improve understanding PFOS's potential illustrate value uncovering mechanisms chemical effects, identifying biomarker candidates, strengthening epidemiological associations, potentially impacting risk assessment.

Язык: Английский

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Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates

Cell Biology and Toxicology, Год журнала: 2024, Номер 40(1)

Опубликована: Авг. 13, 2024

Abstract Many persistent organic pollutants (POPs) are suspected endocrine disruptors and it is important to investigate their effects at low concentrations relevant human exposure. Here, the OECD test guideline #456 steroidogenesis assay was downscaled a 96-well microplate format screen 24 POPs for on viability, testosterone estradiol synthesis using adrenocortical cell line H295R. The compounds (six polyfluoroalkyl substances, five organochlorine pesticides, ten polychlorinated biphenyls three polybrominated diphenyl ethers) were tested human-relevant levels (1 nM 10 µM). Increased synthesis, above threshold of 1.5-fold solvent control, shown after exposure µM PCB-156 (153%) PCB-180 (196%). Interestingly, base hormone varied depending batch. An alternative data analysis linear mixed-effects model that include multiple independent experiments considers batch-dependent variation therefore applied. This approach revealed small but statistically significant or 17 compounds. demonstrated even 1 PCB-74 (18%), PCB-99 (29%), PCB-118 (16%), PCB-138 (19%), (22%), PBDE-153 (21%). MTT viability perfluoroundecanoic acid (12%), 3 (9%), (6%). shows some can interfere with signaling found in blood, highlighting need further investigation into toxicological mechanisms mixtures Graphical

Язык: Английский

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Personalized mixture toxicity testing: A proof-of-principle in vitro study evaluating the steroidogenic effects of reconstructed contaminant mixtures measured in blood of individual adults

Environment International, Год журнала: 2024, Номер 192, С. 108991 - 108991

Опубликована: Авг. 30, 2024

Chemical risk assessments typically focus on single substances, often overlooking real-world co-exposures to chemical mixtures. Mixture toxicology studies using representative mixtures can reveal potential interactions, but these do not account for the unique profiles that occur in blood of diverse individuals. Here we used H295R steroidogenesis assay screen personalized 24 persistent organic pollutants (POPs) cytotoxicity and endocrine disruption. Each mixture was reconstructed at a human exposure relevant concentration (1×), as well 10- 100-fold higher (10×, 100×) by acoustic liquid handling based measured concentrations Swedish cohort. Among twelve tested, nine decreased cell viability 4-18%, primarily highest concentration. While median maximum whole study population induced no measurable effects any concentration, from an individual with lowest total POPs only affected estradiol synthesis (35% increase 100× concentration). Mixtures levels three different individuals stimulated testosterone 1× (11-15%) 10× (12-16%), This proof-of-principle toxicity illustrates population-based may adequately toxicological risks posed It highlights importance testing range explore interactions non-monotonic effects. Further contaminant could improve assessment advance understanding health, exposome data become increasingly available.

Язык: Английский

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