4 research outputs found
Transcriptional and Physiological Responses Induced by Binary Mixtures of Drospirenone and Progesterone in Zebrafish (<i>Danio rerio</i>)
Drospirenone (DRS) is a synthetic
progestin increasingly used in
oral contraceptives with similar effects to progesterone (P4). Wild
fish are exposed to DRS and P4 through wastewater. However, the effects
of DRS on fish, both as an individual compound and in mixtures, have
not been extensively studied. Therefore, in this study, global gene
expression profiles of ovary and brain of female zebrafish (<i>Danio rerio</i>) were characterized after exposure to 55, 553,
and 5442 ng/L DRS for 14 days. The effects were then compared to the
observed responses after exposure to mixtures of DRS and P4 (DRS+P4:
27 + 0.8, 277 + 8 and 3118 + 123 ng/L). Transcriptomics findings were
related to the changes in vitellogenin protein concentrations in the
blood, morphology, and histology of gonads. Multivariate analysis
indicated tissue-, dose-, and treatment-dependent expression profiles.
Genes involved in steroid hormone receptor activity and circadian
rhythm were enriched in DRS and mixture groups, among other pathways.
In mixtures, the magnitude of response was dose- and transcript-dependent,
both at the molecular and physiological levels. Effects of DRS and
P4 were additive for most of the investigated parameters and occurred
at environmentally relevant concentrations. They may translate to
adverse reproductive effects in fish
Disruption of DNA Methylation via <i>S</i>‑Adenosylhomocysteine Is a Key Process in High Incidence Liver Carcinogenesis in Fish
Interactions
between epigenome and the environment in biology and
in disease are of fundamental importance. The incidence of hepatocellular
adenomas in flatfish exceeds 20% in some environments forming a unique
opportunity to study environmental tumorigenesis of general relevance
to cancer in humans. We report the novel finding of marked DNA methylation
and metabolite concentration changes in histopathologically normal
tissue distal to tumors in fish liver. A multi-“omics”
discovery approach led to targeted and quantitative gene transcription
analyses and metabolite analyses of hepatocellular adenomas and histologically
normal liver tissue in the same fish. We discovered a remarkable and
consistent global DNA hypomethylation, modification of DNA methylation
and gene transcription, and disruption of one-carbon metabolism in
distal tissue compared to livers of non-tumor-bearing fish. The mechanism
of this disruption is linked not to depletion of <i>S</i>-adenosylmethionine, as is often a feature of mammalian tumors, but
to a decrease in choline and elevated <i>S</i>-adenosylhomocysteine,
a potent inhibitor of DNA methyltransferase. This novel feature of
normal-appearing tissue of tumor-bearing fish helps to understand
the unprecedentedly high incidence of tumors in fish sampled from
the field and adds weight to the controversial epigenetic progenitor
model of tumorigenesis. With further studies, the modifications may
offer opportunities as biomarkers of exposure to environmental factors
influencing disease
Disruption of DNA Methylation via <i>S</i>‑Adenosylhomocysteine Is a Key Process in High Incidence Liver Carcinogenesis in Fish
Interactions
between epigenome and the environment in biology and
in disease are of fundamental importance. The incidence of hepatocellular
adenomas in flatfish exceeds 20% in some environments forming a unique
opportunity to study environmental tumorigenesis of general relevance
to cancer in humans. We report the novel finding of marked DNA methylation
and metabolite concentration changes in histopathologically normal
tissue distal to tumors in fish liver. A multi-“omics”
discovery approach led to targeted and quantitative gene transcription
analyses and metabolite analyses of hepatocellular adenomas and histologically
normal liver tissue in the same fish. We discovered a remarkable and
consistent global DNA hypomethylation, modification of DNA methylation
and gene transcription, and disruption of one-carbon metabolism in
distal tissue compared to livers of non-tumor-bearing fish. The mechanism
of this disruption is linked not to depletion of <i>S</i>-adenosylmethionine, as is often a feature of mammalian tumors, but
to a decrease in choline and elevated <i>S</i>-adenosylhomocysteine,
a potent inhibitor of DNA methyltransferase. This novel feature of
normal-appearing tissue of tumor-bearing fish helps to understand
the unprecedentedly high incidence of tumors in fish sampled from
the field and adds weight to the controversial epigenetic progenitor
model of tumorigenesis. With further studies, the modifications may
offer opportunities as biomarkers of exposure to environmental factors
influencing disease
The hologenome of <i>Daphnia magna</i> reveals possible DNA methylation and microbiome-mediated evolution of the host genome
Properties that make organisms ideal laboratory models in developmental and medical research are often the ones that also make them less representative of wild relatives. The waterflea Daphnia magna is an exception, by both sharing many properties with established laboratory models and being a keystone species, a sentinel species for assessing water quality, an indicator of environmental change and an established ecotoxicology model. Yet, Daphnia’s full potential has not been fully exploited because of the challenges associated with assembling and annotating its gene-rich genome. Here, we present the first hologenome of Daphnia magna, consisting of a chromosomal-level assembly of the D. magna genome and the draft assembly of its metagenome. By sequencing and mapping transcriptomes from exposures to environmental conditions and from developmental morphological landmarks, we expand the previously annotates gene set for this species. We also provide evidence for the potential role of gene-body DNA-methylation as a mutagen mediating genome evolution. For the first time, our study shows that the gut microbes provide resistance to commonly used antibiotics and virulence factors, potentially mediating Daphnia's environmental-driven rapid evolution. Key findings in this study improve our understanding of the contribution of DNA methylation and gut microbiota to genome evolution in response to rapidly changing environments.</p