Atrazine Exposure Research Articles

Exposure to Atrazine Induces Lung Inflammation through Nrf2-HO1 and Beclin 1/LC3 Pathways.

Atrazine (ATR) is the second most widely used herbicide, after glyphosate, that is used to stop pre- and post-emergence broadleaf and grassy weeds. In 2007, it was included in the class of endocrine disruptors due to the impact its exposure had on human health. Occasional ATR exposure at work has been linked to an increased risk of respiratory problems, but the molecular mechanisms underlying this relationship has not yet been fully elucidated. Mice were exposed to an aerosol containing ATR. In particular ATR aerosol was prepared by dissolving 250 mg of ATR in a vehicle made with saline and 10% DMSO. Seven days after the aerosol exposure, the mice were sacrificed and lung tissue, bronchoalveolar lavage fluid (BALF), and blood samples were collected for histology and biochemical analysis. ATR inhalation induces a generalized state of oxidative/nitrosative stress that leads to an increase in cytokines production and to a physiologically unstable antioxidant defense response evaluated by the alteration of Nrf-2 pathways. Moreover, it stimulates autophagy through Beclin 1/Lc3 expressions and increases lipid peroxidation and apoptosis. All these effects culminate in serious alterations in the tissue architecture of the lungs and to an increase in mucus production and mast cells degranulation. Our study shows, for the first time, the impact of ATR inhalation on lung tissue. This could represent the first step to also recognize this substance as a problematic air pollutant as well as a soil and water contaminant.

Herbicide atrazine exposure induce oxidative stress, immune dysfunction and WSSV proliferation in red swamp crayfish Procambarus clarkii

Atrazine is considered as a potential environmental endocrine disruptors and exhibits various toxic effects on animals. It has a great impact in the aquatic ecosystems, but there are few studies on its immunotoxicity in crustaceans. In the present study, the Procambarus clarkii were utilized to assess the immune toxicity after 0.5 mg/L and 5 mg/L atrazine exposure. A significant decrease in total hemocytes count (THC) was observed at 5 mg/L atrazine exposure throughout the experiment. The activities of antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were significantly inhibited, but the content of reactive oxygen species (ROS) and malondialdehyde (MDA) were up-regulated, indicating the potential oxidative stress. The analysis of the integrated biomarker response (IBR) showed the induction of oxidative stress biomarkers and the inhibition of antioxidants. After 5 mg/L atrazine exposure for 144 h, the integrity of crayfish hepatopancreas was destroyed with disappeared connections between tubules and increased liver tubules vacuoles. The relative expression levels of different immune genes in hepatopancreas after atrazine exposure were measured. Most of these genes were suppressed and exhibited a certain dose-dependent effect. The results of crayfish white spot syndrome virus (WSSV) replication shown the amount of virus in muscle was significantly higher and exhibited a higher mortality rate at 5 mg/L group than other groups. The present study determined the impact of atrazine exposure on WSSV outbreaks, and also provide an important basis for further assessing the occurrence of pesticides on diseases of P. clarkii.

Prolonged exposure to the herbicide atrazine suppresses immune cell functions by inducing spleen cell apoptosis in rats

Atrazine (ATR) is a herbicide used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, ATR exposure is a potential threat to human health. Our previous study showed that subacute exposure to ATR suppresses cellular immune function in mice. In this study, the effects of long-term exposure to ATR on rat immunological system function were measured. Four-week-old female Sprague-Dawley (SD) rats were treated with 0.4 μmol/L, 2 μmol/L and 10 μmol/L ATR for 24 weeks. The results showed that the spleen index increased, white blood cells decreased, and monocytes and eosinophils increased. No obvious changes were detected in the numbers of neutrophils and lymphocytes. Th1, Th2, and Th17 cells decreased significantly, while Treg cells increased after long-term ATR exposure. Moreover, serum levels of cytokines, including TNF-α, INF-γ, IL-6, and IL-12, decreased, while IL-1, IL-4, and IL-5 increased. Degenerative changes and cell apoptosis were found in the spleen; Caspase-3 and Caspase-9 were upregulated, and Bcl-2 was downregulated. These results suggested that long-term ATR exposure may inhibit immune system function.

Role of Fucoidan on the Growth Behavior and Blood Metabolites and Toxic Effects of Atrazine in Nile Tilapia Oreochromis niloticus (Linnaeus, 1758).

Simple SummaryToxic derivatives reach the ponds and cages where fish are grown, and the continuous exposure to these contaminants proved to impair the healthy status of several finfish species. In some countries famous for cultivating rice and corn, atrazine (ATZ) is massively applied to protect plants from invaders. Many functional additives are permitted for application in the aquaculture sector as natural alternatives for chemotherapies. In this study, the toxicity impacts of ATZ and the protective role of fucoidan were investigated on the health performance of Nile tilapia. Long-term exposure to ATZ resulted in low growth rate, impaired hepato-renal function, intestinal inflammation, and oxidative stress in Nile tilapia. However, the obtained results soundly support fucoidan’s potential role to cope with the impacts of ATZ on Nile tilapia.Waterborne herbicides are stressful agents that threaten the productivity and safety of finfish species. In this study, the toxicity impacts of atrazine (ATZ) and the protective role of fucoidan were investigated on the health performance of Nile tilapia. For 40 days, the total number of 180 Nile tilapia was assigned in four groups (triplicates, 15 fish/replicate), where the first (control) and third groups were offered the control diet, while the second and fourth groups were offered a fucoidan (FCN). Further, in the third and fourth groups, the water was mixed with atrazine (ATZ) at 1.39 mg/L daily. The growth rate, FCR, and survival rate were markedly enhanced by fucoidan but severely declined by ATZ exposure (p < 0.05). The morphological structure of the intestine in the control fish revealed normal structure, while fucoidan-treated groups showed eminent enhancement and branching of the intestinal villi. The intestine of ATZ-treated fish revealed deterioration and the intestinal mucosa, inflammatory cell infiltration, and separation of lining epithelium. The highest Hb, PCV, RBCs, WBCs, total protein, and albumin were observed in Nile tilapia fed fucoidan, but the worst values were seen in ATZ-intoxicated fish (p < 0.05). The liver-related enzymes (ALT and AST) and kidney function (urea and creatinine) showed impaired values by ATZ toxicity and were regulated by dietary fucoidan. Meanwhile, fish fed fucoidan and exposed to ATZ had lower total cholesterol and triglyceride values than fish exposed to ATZ without fucoidan feeding (p < 0.05). The SOD, CAT, GPx, cortisol, and glucose levels were increased in ATZ-exposed fish and reduced by fucoidan (p < 0.05). However, the level of malondialdehyde (MDA) was reduced in fucoidan-fed fish and increased in ATZ-exposed fish (p < 0.05). Altogether, dietary fucoidan is required in fish diets to alleviate the impacts of ATZ-induced toxicity.

Symbiotic microalgae do not increase susceptibility of zooxanthellate medusae (Cassiopea xamachana) to herbicides.

Herbicides are among the most detected pesticides in coastal environments. Herbicides may impact non-target organisms, but invertebrates that have a symbiotic relationship with microalgae (zooxanthellae) may be particularly susceptible. How zooxanthellae influence the response of organisms to herbicides, however, remains untested. We exposed zooxanthellate and azooxanthellate Cassiopea xamachana medusae to environmentally relevant concentrations of the herbicide atrazine (0µg L-1, 7µg L-1 and 27µg L-1) for 20 days. We hypothesised that atrazine would have adverse effects on the size, rate of bell contractions and, respiration of medusae, but that effects would be more severe in zooxanthellate than azooxanthellate medusae. We also predicted that photosynthetic efficiency, chlorophyll a (Chla) content and zooxanthellae density would decrease in zooxanthellate medusae exposed to atrazine. Both zooxanthellate and azooxanthellate medusae shrank, yet the size-specific respiration rates were not constant during the experiment. Photosynthetic efficiency of zooxanthellate medusae significantly decreased at 7 and 27 µgL-1 atrazine, but atrazine did not affect the Chla content or zooxanthellae density. Our results showed that even though atrazine inhibited photosynthesis, zooxanthellae were not expelled from the host. We conclude that the presence of zooxanthellae did not increase the susceptibility of C. xamachana medusae to atrazine.

Atrazine detoxification by intracellular crude enzyme extracts derived from epiphytic root bacteria associated with emergent hydrophytes

The present study demonstrated atrazine detoxification by intracellular crude enzyme extracts of Pseudomonas spp. strains ACB and TLB. Indigenous bacterial protein-based remediation techniques could be an alternative to bioaugmentation which pose multiple challenges when applied to the field. Intracellular enzymes were extracted from strains ACB and TLB and their degradation potential of 10 mg L−1 was determined using Gas Chromatography; further, enzyme extracts were subjected to protein profiling studies. In span of 6 h, enzyme extracts of strain ACB showed maximum degradation at 30 °C and 40 °C (71%) and enzyme extracts of strain TLB showed maximum degradation at 40 °C (48%). Atrazine degradation by enzyme extracts of strain ACB showed maximum degradation at pH 7 (71%) and pH 6 (69%) in 6 h. Similarly, enzyme extracts of strain TLB showed maximal degradation at pH 6 (46%) in 6 h. The present study demonstrated, for the first time, efficient atrazine remediation by intracellular crude enzyme extracts from epiphytic root bacteria at a range of temperature and pH conditions. Protein profiling studies indicated that atrazine induced expression of CoA ester lyase and alkyl hydroperoxide reductase in the strains ACB and TLB respectively. Expressions of these proteins have never been associated with atrazine exposure.

Atrazine Promoted Epithelial Ovarian Cancer Cells Proliferation and Metastasis by Inducing Low Dose Reactive Oxygen Species (ROS).

Background: Atrazine (ATZ) is a triazine herbicide that is widely used in agriculture and has been detected in surface and underground water. Recently, laboratory and epidemiological research have found that the bioaccumulation of ATZ in the environment leads to biotoxicity in the human immune and endocrine systems and results in tumor development.Objective: To investigate the effects of ATZ exposure on epithelial ovarian cancer (EOC) cells and elucidate the potential mechanisms governing these effects.Materials and Methods: The human EOC cell lines Skov3 and A2780 were used in this study to explore the effects and mechanisms of ATZ exposure on EOC. The mouse embryonic osteoblastic precursor MC3T3-E1 cells served as the control cells to determine the effects of ATZ on cancer cell lines. After exposure to ATZ, the MTT assay, flow cytometry, the colony formation assay, immunohistochemical staining, the cell scratch assay, and the Transwell assay were used to evaluate the proliferative activity, invasion, and migration capabilities of EOC cell lines. Moreover, flow cytometry was also applied to detect the level of reactive oxygen species (ROS) in these two EOC cell lines, as well as the MC3T3-E1 cells. To further illustrate the underlying mechanisms governing the effect of ATZ on EOC, real-time PCR and Western blotting were employed to assess the transcription and the expression level of Stat3 signaling pathway-related genes in Skov3 and MC3T3-E1 cells.Results: The results showed that following ATZ treatment, the cell proliferation, migration, and invasion potencies of Skov3 and A2780 cells were increased compared to those of the control group. Meanwhile, the ROS levels of EOC and MC3T3-E1 cells were notably elevated after ATZ treatment. In Skov3 cells, the expression levels of p53 and p21 were downregulated, while those of Cyclin E, vascular endothelial growth factor (VEGF), matrix metallopeptidase 2 (MMP2), MMP9, signal transducers and activators of transcription 3 (Stat3), and p-Stat3 were upregulated by ATZ treatment. In MC3T3-E1 cells, however, ATZ treatment did not affect the level of p53/p21 mRNA compared to the control groups. Moreover, there was no significant change in the expression levels of Stat3 and p-Stat3 in MC3T3-E1 cells exposed to ATZ. This phenomenon was observed while the proliferation rate was enhanced in MC3T3-E1 cells by ATZ.Conclusions: The results of this study suggest that ATZ effectively promotes the proliferation and metastasis of EOC cells through the Stat3 signaling pathway by inducing low levels of ROS. Additionally, although ATZ might also induce proliferative potential in normal cells, the mechanisms governing its effects in these cells might be different from those in EOC cells.

Prolonged atrazine exposure beginning in utero and adult uterine morphology in mice.

Through drinking water, humans are commonly exposed to atrazine, a herbicide that acts as an endocrine and metabolic disruptor. It interferes with steroidogenesis, including promoting oestrogen production and altering cell metabolism. However, its precise impact on uterine development remains unknown. This study aimed to determine the effect of prolonged atrazine exposure on the uterus. Pregnant mice (n = 5/group) received 5mg/kg body weight/day atrazine or DMSO in drinking water from gestational day 9.5 until weaning. Offspring continued to be exposed until 3 or 6 months of age (n = 5-9/group), when uteri were collected for morphological and molecular analyses and steroid quantification. Endometrial hyperplasia and leiomyoma were evident in the uteri of atrazine-exposed mice. Uterine oestrogen concentration, oestrogen receptor expression, and localisation were similar between groups, at both ages (P > 0.1). The expression and localisation of key epithelial-to-mesenchymal transition (EMT) genes and proteins, critical for tumourigenesis, remained unchanged between treatments, at both ages (P > 0.1). Hence, oestrogen-mediated changes to established EMT markers do not appear to underlie abnormal uterine morphology evident in atrazine exposure mice. This is the first report of abnormal uterine morphology following prolonged atrazine exposure starting in utero, it is likely that the abnormalities identified would negatively affect female fertility, although mechanisms remain unknown and require further study.

Effect of atrazine on accumulation of iron via the iron transport proteins in the midbrain of SD rats.

Atrazine (ATR), a widely used herbicide that belongs to the triazine class, has detrimental effects on several organ systems. It has also been shown that ATR exposure results in dopaminergic neurotoxicity. However, the mechanism of herbicides causing ferroptosis in neurons is less concerned. So, the present study aimed to investigate the effects of long-term oral exposure to ATR on ferroptosis in adult male rats. In this study, we show that there was a dose-dependent increase in the concentration of iron in the midbrain. Simultaneously, the expression of tyrosine hydroxylase (TH) and Synuclein (α-syn) were altered by the ATR. We carried out miRNA profiling brain tissue in order to identify factors that mediate ferroptosis. We also found that the mRNA and protein expression of the transferrin receptor (TFR), divalent metal transporter 1 (DMT1), hephaestin (HEPH), and ferroportin 1 (Fpn1) in the midbrain were affected by ATR. Based on the current results and previously published data, it is clear that exposure of adult male rats to high doses of ATR leads to iron loading in the midbrain. The long-term adverse effects of ATR on the midbrain have a special relevance after exposure.

Meta-analysis and experimental validation identified atrazine as a toxicant in the male reproductive system.

Atrazine (ATZ), as a widely used triazine herbicide, is an environmental endocrine disruptor (EDC) that can cause many health problems. Therefore, we conducted this study based on the evidence of rats and mice to figure out the characteristics of ATZ damage to the reproductive system and further evaluate its health effects on the human. PRISMA's guidelines were followed according to the principles recommended by the Cochrane Handbook for Systematic Review. Health assessment was performed using the OHAT approach. Our new data were obtained from randomized controlled trials in rats designed in accordance with toxicological guidelines. Exposure to ATZ was significantly associated with decreased testosterone production (SMD = - 0.90, 95% CI - 1.27 to - 0.53), and reduced absolute weights of testis (SMD = - 0.41, 95% CI - 0.61 to - 0.22) and other reproductive organs. The damaging effect of sperm quality was also observed clearly, which included reduction of sperm count both in epididymis (SMD = - 2.32, 95% CI - 2.83 to - 1.81) and testis (SMD = - 1.01, 95% CI - 1.37 to - 0.64), decrease in sperm motility (SMD = - 8.86, 95% CI - 10.88 to - 6.83), and increase in sperm abnormality. Subgroup analysis revealed consistency across different species, life stage, and dosage. In addition, we found that ATZ exposure at a daily dose of 120 mg/kg during adolescence could cause decrease in weight gain and histological damage to the testis. The gene expression levels of Nrf2/HO-1 and Bcl-2/caspase signaling pathways in testis tissues were changed significantly. The results of this SR indicated that exposure to ATZ was associated with impairment of male reproductive system in rodents regardless of species, exposure life stage, and dosage. It is believed that ATZ exposure may have similar effects on male reproductive system of human beings. Pathways related to oxidative stress and apoptosis may be the mechanism leading to testicular damage in rats treated with ATZ.

Developmental atrazine exposure in zebrafish produces the same major metabolites as mammals along with altered behavioral outcomes

Atrazine (ATZ) is the second most commonly applied agricultural herbicide in the United States. Due to contamination concerns, the U.S. EPA has set the maximum contaminant level in potable water sources at 3 parts per billion (ppb; μg/l). Depending on the time of year and sampling location, water sources often exceed this limit. ATZ is an endocrine disrupting chemical in multiple species observed to target the neuroendocrine system. In this study the zebrafish vertebrate model was used to test the hypothesis that a developmental ATZ exposure generates metabolites similar to those found in mammals and alters morphology and behavior in developing larvae. Adult AB zebrafish were bred, embryos were collected, and exposed to 0, 0.3, 3, or 30 ppb ATZ from 1 to 120 h post fertilization (hpf). Targeted metabolomic analysis found that zebrafish produce the same major ATZ metabolites as mammals: desethyl atrazine (DEA), deisopropyl atrazine (DIA), and diaminochloroatrazine (DACT). The visual motor response test at 120 hpf detected hyperactivity in larvae in the 0.3 ppb treatment group and hypoactivity in the 30 ppb treatment group (p < 0.05). Further analysis into behavior during the dark and light phases showed zebrafish larvae exposed to 0.3 ppb ATZ had an increase in total distance moved in the first light phase and time spent moving in the first dark and light phases (p < 0.05). Alternatively, a decrease in total distance moved was observed in the second and third dark phases in zebrafish exposed to 30 ppb ATZ (p < 0.05). No significant differences were observed for any of the morphological measurements following ATZ exposure from 1 to 120 hpf (p > 0.05). These findings suggest that a ATZ exposure during early development generates metabolite profiles similar to mammals and leads to behavioral alterations supporting ATZ as a neurodevelopmental toxicant.

Effects of multiple stressors on northern leopard frogs in agricultural wetlands.

Natural and anthropogenic stressors, including parasites and pesticides, may induce oxidative stress in animals. Measuring oxidative stress responses in sentinel species that are particularly responsive to environmental perturbations not only provides insight into host physiology but is also a useful readout of ecosystem health. Newly metamorphosed northern leopard frogs (Lithobates pipiens), a sentinel species, were collected from agricultural and non-agricultural wetlands exposed to varying concentrations of the herbicide atrazine. Significant effects of certain parasites' abundance and their interaction with atrazine exposure on frog oxidative stress were identified. Specifically, increased protein levels were detected in frogs infected with echinostome metacercariae. In addition, the nematode Oswaldocruzia sp. was significantly associated with increased thiol concentration and catalase activity. Significant parasite × atrazine interactions were observed for atrazine exposure and the abundance of Oswaldocruzia sp. on thiol, as thiol concentrations increased with parasite abundance at low atrazine localities and decreased in high atrazine wetlands. In addition, a significant interaction between the abundances of Oswaldocruzia sp. and gorgoderid trematodes on thiol concentrations was observed. These findings demonstrate that studies of oxidative stress on animals in natural ecosystems should account for the confounding effects of parasitism, particularly for amphibians in agricultural landscapes.

Exposure to Atrazine Impairs Behaviour and Growth Performance in African Catfish, Clarias gariepinus (Burchell, 1822) Juveniles

Clarias gariepinus juveniles of average weight, 17.57±1.95 g and an average length of 14.26±0.39 cm were exposed to environmentally relevant concentrations of 0 (control), 2.5, 25, 250, and 500 µg L-1 atrazine in a quality-controlled 28-day bioassay. Growth performance was assessed bi-weekly and fish samples were taken from different tanks to determine the relative growth rate, specific growth rate, feed conversion ratio, condition factor and behaviour. At the end of two weeks of exposure, the relative growth rate and the specific growth rate among exposed fish groups was found to reduce significantly (p&lt;0.05) compared to the control, an indication of poor growth performance. The average specific growth rates (SGR) of control fish is 3.86±0.02 %/w at the end of the exposure duration while recording -0.64±0.09 in the 500 µg L-1 group. Feed conversion ratio increased significantly from control to the group with highest atrazine concentration. Condition factor (K) of fish among treatment groups showed significant decrease in values with increasing concentration of atrazine in a dose-dependent pattern. Atrazine exposure resulted in behavioural anomalies including erratic swimming, clinging to the water surface, loss of equilibrium, lethargy, and discolouration. The behavioural responses were found to be concentration-dependent. The length-weight relationships for both control and atrazine exposed fish exhibited positive allometric growth and significant relationships as depicted by the value of R2 (coefficient of determination) except in the fish group exposed to 500 µg L-1 atrazine which exhibited negative allometric growth. Findings from this study indicate interference with normal behaviour and growth performance of C. gariepinus juveniles with ecological implications in water bodies exposed to atrazine even at reduced concentrations.

Prenatal exposure to atrazine induces cryptorchidism and hypospadias in F1 male mouse offspring.

The main objective of the present study was to determine whether prenatal exposure to atrazine could affect testicle descent and penile masculinization. Atrazine has been demonstrated with a variety of endocrine disrupting activities and reproductive toxicities. However, the effects of prenatal atrazine exposure on male offspring's genital malformation, such as hypospadias and cryptorchidism, remain poorly understood. In this study, pregnant ICR mice were gavaged from gestational day 12.5–16.5 with different doses of atrazine. Although no sign of systemic toxicity was observed in F1 male pups, prenatal exposure to 100 mg/kg/day atrazine affected penile morphology, urethral meatus position and descent of testis, and reduced anogenital distance and penile size in postnatal day 21 F1 male pups. The comparative study with an androgen receptor (AR) antagonist vinclozolin suggested that these effects of atrazine on male genital development may not be through antagonism of AR. The results also revealed that atrazine exposure significantly reduced maternal serum testosterone levels, decreased AR nuclear translocation, and altered the expression levels of developmental gene networks in developing penis of mice. Atrazine exposure also affected the expression of insulin‐like 3 (Insl3) and steroidogenic gene expression in developing reproductive tract. Therefore, our data indicate that prenatal atrazine exposure can induce hypospadias in F1 mice, likely through disruption of testosterone production, decreasing genomic androgen action, and then altering expression of developmental genes during sexual differentiation. Our data also suggest that prenatal atrazine exposure can induce cryptorchidism in F1 mice, possibly through down regulation of Insl3.

The tensile root strength of Spartina patens declines with exposure to multiple stressors

Coastal wetlands may be subjected to numerous biotic and abiotic stressors from natural and anthropogenic forces in the landscape. The influx of nutrients, inorganic compounds and xenobiotics are suspected of degrading the belowground biomass of coastal macrophytes. Spartina patens acts as an ecosystem engineer for lower salinity coastal marshes and its biomechanical properties are vital to the stability and resilience of coastal wetlands. S.patens was exposed to one natural (flooding) and two anthropogenic stressors (atrazine and nutrient addition) in a greenhouse experiment to test the hypothesis that these three stressors reduce the tensile root strength of S. patens. A one-way Welch’s analysis of variance revealed that the tensile root strength S. patens significantly declined after exposure to two flood duration regimes, three levels of atrazine exposure, and two levels of nutrient addition that consisted of nitrogen-phosphorus combinations. A one-way ANOVA of tensile root strength with an atrazine-flood duration-nutrient addition combination treatment as the main effect resulted in a 52 to 63% loss in tensile strength, while the individual atrazine, flooding, and nutrient treatments produced 40, 39, and 37% losses in tensile root strength, respectively. These results indicate that the effects of multiple natural and/or anthropogenic stressors may degrade the tensile root strength of S. patens, which could facilitate coastal erosion and subsequent collapse of the wetland ecosystem.

Pre-differentiation exposure to low-dose of atrazine results in persistent phenotypic changes in human neuronal cell lines.

Exposures to organic pesticides, particularly during a developmental window, have been associated with various neurodegenerative diseases later in life. Atrazine (ATZ), one of the most used pesticides in the U.S., is suspected to be associated with increased neurodegeneration later in life but few studies assessed the neurotoxicity of developmental ATZ exposure using human neuronal cells. Here, we exposed human SH-SY5Y cells to 0.3, 3, and 30ppb of ATZ prior to differentiating them into dopaminergic-like neurons in ATZ-free medium to mimic developmental exposure. The differentiated neurons exhibit altered neurite outgrowth and SNCA pathology depending on the ATZ treatment doses. Epigenome changes, such as decreases in 5mC (for 0.3ppb only), H3K9me3, and H3K27me3 were observed immediately after exposure. These alterations persist in a compensatory manner in differentiated neurons. Specifically, we observed significant reductions in 5mC and H3K9me3, as well as, an increase in H3K27me3 in ATZ-exposed cells after differentiation, suggesting substantial chromatin rearrangements after developmental ATZ exposure. Transcriptional changes of relevant epigenetic enzymes were also quantified but found to only partially explain the observed epigenome alteration. Our results thus collectively suggest that exposure to low-dose of ATZ prior to differentiation can result in long-lasting changes in epigenome and increase risks of SNCA-related Parkinson's Disease.

Chronic Atrazine Exposure Beginning Prenatally Impacts Liver Function and Sperm Concentration With Multi-Generational Consequences in Mice.

Atrazine is a commonly used herbicide frequently detected in waterways and drinking water around the world. Worryingly, atrazine is an endocrine and metabolic disruptor but there is a lack of research regarding the effects of long-term exposure beginning in utero. In this study we investigated how chronic exposure to atrazine (5 mg/kg bw/day) in drinking water from E9.5 until 12 or 26 weeks of age affected metabolic and reproductive characteristics in male mice. We then examined whether mating these males to unexposed females altered in vitro embryo characteristics. Atrazine exposure caused a decrease in liver weight and changes in both liver and testis gene expression, specifically in genes involved in lipid uptake and fatty acid metabolism in the liver, as well as androgen conversion in the testis. Notably, atrazine exposure decreased epididymal sperm concentration and subsequent embryo cell numbers generated from the 12-week cohort males. Collectively, these data suggest that atrazine exposure, beginning prenatally, affects both metabolic and reproductive characteristics, and highlights the importance of assessing atrazine effects at different life stages and over multiple generations. The continued widespread use of atrazine warrants further studies, as it is essential to understand the health risks for all species, including humans.

Biomarkers response and population biological parameters in the earthworm Eisenia fetida after short term exposure to atrazine herbicide

Atrazine is one of the most used herbicides and its over-application in fields can affect the soils and their associated biota. In this work, earthworms (Eisenia fetida) were exposed to different concentrations of atrazine to assess possible sublethal harmful effects. In the search for reliable biomarkers of these effects, acetylcholinesterase (AChE), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities were measured as well as behaviour and population biological parameters such as biomass, growth and production of cocoons. It was found that biomass changes were not significantly affected by atrazine presence and after 28 days the increment was around 18.3–27.3%. Protein content in earthworms was reduced in the presence of atrazine after 28 days. The lower atrazine concentration (2 mg Kg−1) affected in the shortest term (7 days) the rate of cocoon production and increased LDH activity and, especially, the AChE activity in around 40%. The presence of a higher concentration (10 mg Kg−1) of the herbicide reduced one third of the number of total cocoons, affecting the reproduction. ALP was the least sensitive biomarker to atrazine exposure. When exposed to up to 10 mg Kg−1 of atrazine, E. fetida showed a tendency to rebalance and maintained its general health.

Effects of subchronic exposure to environmentally relevant concentrations of the herbicide atrazine in the Neotropical fish Astyanax altiparanae

Atrazine (ATZ) is among the most widely used herbicides in the world, and yet it has a potential to contaminate aquatic environments due to pesticide leaching from agricultural areas. In the Neotropical region, studies about the effects of this herbicide in native aquatic wildlife is scarce.Our study aimed at investigating the effects of a 30-day exposure to a commercial atrazine formulation on oxidative stress parameters, histopathology in testis and liver, and hormone levels in males and female of yellow-tailed tetra fish (Astyanax altiparanae). Adults were exposed to low but environmentally relevant concentrations of atrazine as follows: 0 (CTL-control), 0.5 (ATZ0.5), 1 (ATZ1), 2 (ATZ2) and 10 (ATZ10) μg/L. Our results showed decreased GST activity in gills in all groups of exposed animals and increased CAT activity in gills from the ATZ10 group. In the liver, there was an increase in lipid peroxidation in fish from ATZ1 and ATZ2 groups. Histological analysis of the liver showed increased percentage of sinusoid capillaries in ATZ2 fish, increased vascular congestion in ATZ1 and increased leukocyte infiltration in the ATZ10 group. Hepatocyte diameter analysis revealed a decrease in cell size in all groups exposed to ATZ, and a decrease in hepatocyte nucleus diameter in ATZ1, ATZ2 and ATZ10 groups. Endocrine parameters did not show significant changes following ATZ exposure, although an increase of triiodothyronine/thyroxine (T3/T4) ratio was observed in ATZ2 fish. Our results provide evidence that even low, environmentally relevant concentrations of ATZ produced oxidative damage and histological alterations in adult yellow-tailed tetra.

Identification of a novel function of a component in the jasmonate signaling pathway for intensive pesticide degradation in rice and environment through an epigenetic mechanism.

Developing a biotechnical system with rapid degradation of pesticide is critical for reducing environmental, food security and health risks. Here, we investigated a novel epigenetic mechanism responsible for the degradation of the pesticide atrazine (ATZ) in rice crops mediated by the key component CORONATINE INSENSITIVE 1a (OsCOI1a) in the jasmonate-signaling pathway. OsCOI1a protein was localized to the nucleus and strongly induced by ATZ exposure. Overexpression of OsCOI1a (OE) significantly conferred resistance to ATZ toxicity, leading to the improved growth and reduced ATZ accumulation (particularly in grains) in rice crops. HPLC/Q-TOF-MS/MS analysis revealed increased ATZ-degraded products in the OE plants, suggesting the occurrence of vigorous ATZ catabolism. Bisulfite-sequencing and chromatin immunoprecipitation assays showed that ATZ exposure drastically reduced DNA methylation at CpG context and histone H3K9me2 marks in the upstream of OsCOI1a. The causal relationships between the DNA demethylation (hypomethylatioin), OsCOI1a expression and subsequent detoxification and degradation of ATZ in rice and environment were well established by several lines of biological, genetic and chemical evidence. Our work uncovered a novel regulatory mechanism implicated in the defense linked to the epigenetic modification and jasmonate signaling pathway. It also provided a modus operandi that can be used for metabolic engineering of rice to minimize amounts of ATZ in the crop and environment.