Microplastics (MPs) are widespread contaminants in aquatic ecosystems and pose significant threats to both organisms and the environment. Their small size, high surface area, and capacity to adsorb toxic chemicals allow MPs to infiltrate food webs, affecting organisms across trophic levels. This review explores the intricate mechanisms by which MPs induce reproductive and endocrine toxicity, focusing on their physical and chemical properties, bioaccumulation dynamics, and associated molecular pathways. MPs interfere with hormonal homeostasis, oxidative stress responses, and apoptotic pathways, leading to disruptions in the hypothalamic-pituitary-gonadal axis, impaired steroidogenesis, and gonadal dysfunction. These effects manifest as reduced fertility, altered gametogenesis, and multigenerational reproductive impairments across diverse aquatic taxa. Furthermore, MPs serve as carriers for endocrine-disrupting chemicals, compounding their adverse effects on organisms and aquatic biodiversity. Through a synthesis of recent research, this review identifies key signaling pathways, including MAPK, PI3K-AKT, mTOR, NF-κB, PPAR and NLRP3 inflammasome, that may play a role in MP-induced reproductive toxicity. The findings underscore the urgent need for advanced mitigation strategies, regulatory frameworks, and further research to combat the ecological consequences of MP pollution. Prioritizing targeted interventions is essential to safeguard aquatic biodiversity and ensure ecosystem resilience against the pervasive threat of MPs.

• Klíčová slova
• Endocrine system, Microplastics, Oxidative stress, Reproduction,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Perfluorooctanoic acid (PFOA), a member of per- and polyfluoroalkyl substances (PFASs), has been widely used in manufacturing for decades. Currently, PFOA is strictly regulated, but due to its high stability and persistence, it is detected in both environmental as well as in human matrices. To elucidate mechanisms of PFOA toxicity in humans, we determined the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMC) responding to PFOA exposure in a sex-stratified analysis. This work employed samples from 145 female and 143 male participants of the CELSPAC: YA study to characterize PFOA-associated transcripts in a broader context using computational analysis. PFOA-associated gene expression differed significantly between men and women, as only 2 % of mapped genes were expressed in both sexes. Disease-specific enrichment analysis revealed cancer and immune-related disease terms as those most enriched in male and female populations. Patterns of enriched terms within the gene set enrichment analysis indicated three main targets of PFOA toxicity: i) lipid metabolism for women; ii) cell cycle regulation for men; and iii) immune system response for both sexes. In summary, our genome-wide transcriptomics analysis described sex-specific differences in PFOA-associated gene expression and provided evidence about biological pathways underlying PFOA toxicity in humans.

• Klíčová slova
• Enrichment analysis, Perfluorooctanoic acid, Peripheral blood mononuclear cells, Sex differences, Transcriptome,
• MeSH
• dospělí MeSH
• exprese genu účinky léků   MeSH
• fluorokarbony * toxicita   MeSH
• kapryláty * toxicita   MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• leukocyty mononukleární účinky léků   metabolismus   MeSH
• lidé MeSH
• mladý dospělý MeSH
• transkriptom účinky léků   MeSH
• vystavení vlivu životního prostředí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• fluorokarbony * MeSH
• kapryláty * MeSH
• látky znečišťující životní prostředí MeSH
• perfluorooctanoic acid MeSH Prohlížeč

While the immunomodulation effects of per- and polyfluoroalkyl substances (PFASs) are described on the level of clinical signs in epidemiological studies (e.g., suppressed antibody response after vaccination), the underlying mechanism has still not been fully elucidated. To reveal mechanisms of PFAS exposure on immunity, we investigated the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMCs) responding to PFAS exposure (specifically, exposure to PFPA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS). Blood samples and the chemical load in the blood were analyzed under the cross-sectional CELSPAC: Young Adults study. The overall aim of the study was to identify sensitive gene sets and cellular pathways conserved for multiple PFAS chemicals. Transcriptome networks related to adaptive immunity were perturbed by multiple PFAS exposure (i.e., blood levels of at least four PFASs). Specifically, processes tightly connected with late B cell development, such as B cell receptor signaling, germinal center reactions, and plasma cell development, were shown to be affected. Our comprehensive transcriptome analysis identified the disruption of B cell development, specifically the impact on the maturation of antibody-secreting cells, as a potential mechanism underlying PFAS immunotoxicity.

• Klíčová slova
• B cell, Perfluoroalkyl substances, adult cohort, gene expression, immunotoxicity, peripheral blood mononuclear cells, plasma cell, transcriptomics,
• MeSH
• fluorokarbony * toxicita   MeSH
• kyseliny alkansulfonové * MeSH
• látky znečišťující životní prostředí * MeSH
• leukocyty mononukleární MeSH
• lidé MeSH
• mladý dospělý MeSH
• průřezové studie MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• fluorokarbony * MeSH
• kyseliny alkansulfonové * MeSH
• látky znečišťující životní prostředí * MeSH

The physiology of males and females can be vastly different, complicating interpretation of toxicological and physiological data. The objectives of this study were to elucidate the sex differences in the microbiome-gastrointestinal (GI) transcriptome of adult zebrafish. We compared microbial composition and diversity in both males and females fed the same diet and housed in the same environment. There were no sex-specific differences in weight gain nor gastrointestinal morphology based on histopathology. There was no difference in gut microbial diversity, richness (Shannon and Chao1 index) nor predicted functional composition of the microbiome between males and females. Prior to post-hoc correction, male zebrafish showed higher abundance for the bacterial families Erythrobacteraceae and Lamiaceae, both belonging to the phyla Actinobacteria and Proteobacteria. At the genus level, Lamia and Altererythrobacter were more dominant in males and an unidentified genus in Bacteroidetes was more abundant in females. There were 16 unique differentially expressed transcripts in the gastrointestinal tissue between male and female zebrafish (FDR corrected, p < 0.05). Relative to males, the mRNA expression for trim35-9, slc25a48, chchd3b, csad, and hsd17b3 were lower in female GI while cyp2k6, adra2c, and bckdk were higher in the female GI. Immune and lipid-related gene network expression differed between the sexes (i.e., cholesterol export and metabolism) as well as networks related to gastric motility, gastrointestinal system absorption and digestion. Such data provide clues as to putative differences in gastrointestinal physiology between male and female zebrafish. This study identifies host-transcriptome differences that can be considered when interpreting the microgenderome of zebrafish in studies investigating GI physiology and toxicology of fishes.

• Klíčová slova
• Experimental design, Gastrointestinal system, Gene networks, Microgenderome, Sex differences,
• MeSH
• Bacteria MeSH
• dánio pruhované genetika   MeSH
• gastrointestinální trakt mikrobiologie   MeSH
• mikrobiota * MeSH
• proteiny regulující apoptózu MeSH
• střevní mikroflóra * genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteiny regulující apoptózu MeSH

• Klíčová slova
• chemicals, evolution, fish, microbiome, microbiomics, physiology,
• MeSH
• mikrobiota * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• úvodníky MeSH

Transcriptome data were collected in rat dopamine cells exposed to fipronil for 24 h using microarray analysis. Fipronil is a phenylpyrazole pesticide that acts to inhibit gamma-aminobutyric acid (GABA), blocking inhibitory synaptic transmission in the central nervous system. Transcriptome data were subjected to pathway analysis and subnetwork enrichment analysis. We report that 25 µM fipronil altered transcriptional networks in dopamine-synthesizing cells that are associated with Alzheimer's Disease, Huntington Disease, and Schizophrenia. Data analysis revealed that nerve fibre degeneration, nervous system malformations, neurofibrillary tangles, and neuroinflammation were all disease processes related to the transcriptome profile observed in the rat neuronal cells. Other disease networks altered by fipronil exposure at the transcript level were associated with the mitochondria, including mitochondrial DNA depletion syndrome and mitochondrial encephalomyopathies. These data, along with those presented in Souders et al. (2021), are significant because they increase understanding into the molecular mechanisms underlying human disease following exposures to neuroactive pesticides. These data can be reused to inform adverse outcome pathways for neurotoxic pesticides.

• Klíčová slova
• Alzheimer's disease, Gene expression, Interactome, Neurodegeneration, Neurotoxicology, Pesticides,
• Publikační typ
• časopisecké články MeSH

Water contaminated with plastic debris and leached plasticizers can be ingested or taken up by aquatic invertebrates and vertebrates alike, exerting adverse effects on multiple tissues including the gastrointestinal tract. As such, gut microbiomes of aquatic animals are susceptible targets for toxicity. Recent studies conducted in teleost fishes report that microplastics and plasticizers (e.g., phthalates, bisphenol A) induce gastrointestinal dysbiosis and alter microbial diversity in the gastrointestinal system. Here we synthesize the current state of the science regarding plastics, plasticizers, and their effects on microbiomes of fish. Literature suggests that microplastics and plasticizers increase the abundance of opportunistic pathogenic microorganisms (e.g. Actinobacillus, Mycoplasma and Stenotrophomonas) in fish and reveal that gamma-proteobacteria are sensitive to microplastics. Recommendations moving forward for the research field include (1) environmentally relevant exposures to improve understanding of the long-term impacts of microplastic and plasticizer contamination on the fish gastrointestinal microbiome; (2) investigation into the potential impacts of understudied polymers such as polypropylene, polyamide and polyester, and (3) studies with elastomers such as rubbers that are components of tire materials, as these chemicals often dominate plastic debris. Focus on both microplastics and the gut microbiota is intensifying in environmental toxicology, and herein lies an opportunity to improve evaluation of global ecological impacts associated with plastic contamination. This is important as the microbiota is intimately tied to an individual's health and fragmentation of microbial community networks and gut dysbiosis can result in disease susceptibility and early mortality events.

• Klíčová slova
• Bisphenol A, Gastrointestinal system, Immunity, Microbiome, Phthalate, Rubber,
• MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• ekotoxikologie * MeSH
• mikroplasty toxicita   MeSH
• monitorování životního prostředí MeSH
• ryby růst a vývoj   mikrobiologie   MeSH
• střevní mikroflóra * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH
• mikroplasty MeSH

The phenylpyrazole fipronil is an insecticide that inhibits γ -amino-butyric acid (GABA) ionotropic receptors in the central nervous system. Experimental evidence suggests that fipronil acts as a neurotoxin and it is implicated in neurodegenerative diseases; however, the mechanisms of neurotoxicity are not fully elucidated. The objective of this study was to quantify mechanisms of fipronil-induced neurotoxicity in dopamine cells. Rat primary immortalized mesencephalic dopaminergic cells (N27) were treated with fipronil (0.25 up to 500 μM depending on the assay). We measured endpoints related to mitochondrial bioenergetics, mitophagy, mitochondrial membrane potential, and ATP production in addition to discerning transcriptome responses to the pesticide. Fipronil reduced cell viability at 500 μM after 24 h exposure and caspase 3/7 activity was significant increased after 6 and 12 h by 250 and 500 μM fipronil. Subsequent endpoints were thus assessed at concentrations that were below cytotoxicity. We measured oxidative respiration of N27 cells following a 24 h exposure to one dose of either 0.25, 2.5, 25, or 50 μM fipronil. Oxygen consumption rates (OCR) were not different between vehicle-control and 0.25 or 2.5 μM fipronil treatments, but there was a ∼40-60 % reduction in basal respiration, as well as reduced oligomycin-induced ATP production at 50 μM. The reduction in OCR is hypothesized to be related to lower mitochondrial mass due to mitophagy. Mitochondrial membrane potential was also sensitive to fipronil, and it was compromised at concentrations of 2.5 μM and above. To further elucidate the mechanisms linked to neurotoxicity, we conducted transcriptomics in dopamine cells following treatment with 25 μM fipronil. Fipronil suppressed transcriptional networks associated with mitochondria (damage, depolarization, permeability, and fission), consistent with its effects on mitochondrial membrane potential. Altered gene networks also included those related to Alzheimer disease, inflammatory disease, nerve fiber degeneration, and neurofibrillary tangles. This study clarifies molecular targets of fipronil-induced neurotoxicity and supports, through multiple lines of evidence, that fipronil acts as a mitochondrial toxicant in dopamine cells. This is relevant to neurodegenerative diseases like Parkinson's disease as exposure to fipronil is associated with the progressive loss of nigrostriatal dopaminergic neurons in rodents.

• Klíčová slova
• Apoptosis, Mitochondrial bioenergetics, Parkinson’s disease, Pathway analysis, Pesticides, Transcriptomics,
• MeSH
• dopaminergní neurony účinky léků   metabolismus   MeSH
• insekticidy toxicita   MeSH
• krysa rodu Rattus MeSH
• membránový potenciál mitochondrií účinky léků   fyziologie   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• pyrazoly toxicita   MeSH
• transformované buněčné linie MeSH
• transkriptom účinky léků   fyziologie   MeSH
• viabilita buněk účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fipronil MeSH Prohlížeč
• insekticidy MeSH
• pyrazoly MeSH

Aquatic ecosystems are under increasing stress from global anthropogenic and natural changes, including climate change, eutrophication, ocean acidification, and pollution. In this critical review, we synthesize research on the microbiota of aquatic vertebrates and discuss the impact of emerging stressors on aquatic microbial communities using two case studies, that of toxic cyanobacteria and microplastics. Most studies to date are focused on host-associated microbiomes of individual organisms, however, few studies take an integrative approach to examine aquatic vertebrate microbiomes by considering both host-associated and free-living microbiota within an ecosystem. We highlight what is known about microbiota in aquatic ecosystems, with a focus on the interface between water, fish, and marine mammals. Though microbiomes in water vary with geography, temperature, depth, and other factors, core microbial functions such as primary production, nitrogen cycling, and nutrient metabolism are often conserved across aquatic environments. We outline knowledge on the composition and function of tissue-specific microbiomes in fish and marine mammals and discuss the environmental factors influencing their structure. The microbiota of aquatic mammals and fish are highly unique to species and a delicate balance between respiratory, skin, and gastrointestinal microbiota exists within the host. In aquatic vertebrates, water conditions and ecological niche are driving factors behind microbial composition and function. We also generate a comprehensive catalog of marine mammal and fish microbial genera, revealing commonalities in composition and function among aquatic species, and discuss the potential use of microbiomes as indicators of health and ecological status of aquatic ecosystems. We also discuss the importance of a focus on the functional relevance of microbial communities in relation to organism physiology and their ability to overcome stressors related to global change. Understanding the dynamic relationship between aquatic microbiota and the animals they colonize is critical for monitoring water quality and population health.

• Klíčová slova
• aquatic mammals, biomonitoring, ecosystem health, fish, microbiome, stressors,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Dietary exposure to chemicals alters the diversity of microbiome communities and can lead to pathophysiological changes in the gastrointestinal system. The organochlorine pesticide dieldrin is a persistent environmental contaminant that bioaccumulates in fatty tissue of aquatic organisms. The objectives of this study were to determine whether environmentally-relevant doses of dieldrin altered gastrointestinal morphology and the microbiome of zebrafish. Adult zebrafish at ∼4 months of age were fed a measured amount of feed containing either a solvent control or one of two doses of dieldrin (measured at 16, and 163.5 ng/g dry weight) for 4 months. Dieldrin body burden levels in zebrafish after four-month exposure were 0 (control), 11.47 ± 1.13 ng/g (low dose) and 18.32 ± 1.32 ng/g (high dose) wet weight [mean ± std]. Extensive histopathology at the whole organism level revealed that dieldrin exposure did not induce notable tissue pathology, including the gastrointestinal tract. A repeated measure mixed model analysis revealed that, while fish gained weight over time, there were no dieldrin-specific effects on body weight. Fecal content was collected from the gastrointestinal tract of males and 16S rRNA gene sequencing conducted. Dieldrin at a measured feed dose of 16 ng/g reduced the abundance of Firmicutes, a phylum involved in energy resorption. At the level of class, there was a decrease in abundance of Clostridia and Betaproteobacteria, and an increase in Verrucomicrobiae species. We used a computational approach called predicted relative metabolomic turnover (PRMT) to predict how a shift in microbial community composition affects exchange of metabolites. Dieldrin was predicted to affect metabolic turnover of uroporphyrinogen I and coproporphyrinogen I [enzyme]-cysteine, hydrogen selenide, selenite, and methyl-selenic acid in the fish gastrointestinal system. These pathways are related to bacterial heme biosynthesis and selenium metabolism. Our study demonstrates that dietary exposures to dieldrin can alter microbiota composition over 4 months, however the long-term consequences of such impacts are not well understood.

• Klíčová slova
• Aquatic, Ecotoxicology, Microbiome, Pathology, Pesticide,
• MeSH
• dánio pruhované MeSH
• dieldrin toxicita   MeSH
• gastrointestinální trakt MeSH
• hem MeSH
• mikrobiota * MeSH
• RNA ribozomální 16S MeSH
• selen * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dieldrin MeSH
• hem MeSH
• RNA ribozomální 16S MeSH
• selen * MeSH