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Apoptosis and blood-testis barrier disruption during male reproductive dysfunction induced by PAHs of different molecular weights
2022
Zhang, Lin | Ji, Xiaoli | Ding, Fan | Wu, Xuan | Tang, Ning | Wu, Qing
The association between polycyclic aromatic hydrocarbons (PAHs) and male reproductive dysfunction has attracted increasing attention. The purpose of this study was to compare the male reproductive toxicity of multiple PAHs and to investigate the underlying molecular mechanisms. TM4 cells (mouse testicular Sertoli cells, SCs) were treated with benzo(a)pyrene (BaP), pyrene (Py), fluoranthene (Fl) and phenanthrene (Phe) (0, 0.1, 1, 10, 50, or 100 μM) for varying time points (4, 12, 24, or 48 h), and male C57BL/6 mice were administered BaP and Py (0, 10, 50, or 100 mg/kg body weight) for 14 days based on the cell experimental results. Histopathological examination, western blotting, ELISA, biochemical assays, RT–PCR, flow cytometry, JC-1 staining and trans-epithelium electrical resistance (TEER) measurements were used to assess apoptosis, blood-testis barrier (BTB) integrity, intracellular calcium ([Ca²⁺]ᵢ) concentrations and oxidative stress (OS). The results revealed that the mRNA levels and enzymatic activities of CYP450 and GST family members; levels of ROS, MDA, cleaved caspase 3 (c-caspase 3), caspase 9, Bax, and cytochrome C (CytC); and numbers of TUNEL-positive cells were significantly increased by BaP and Py, while levels of AhR, GSH, SOD, CAT, Bcl-2 and ΔΨm were decreased. Additionally, BaP and Py notably interfered with tight junctions (TJs) and adherens junctions (AJs) in the BTB. Intriguingly, BaP, but not Py, induced [Ca²⁺]ᵢ overload and gap junction (GJ) destruction. There was no dramatic effect of Fl and/or Phe on any of the above parameters except that slight cytotoxicity was observed with higher doses of Fl. Collectively, these findings showed that BaP and Py elicited SC apoptosis and BTB disruption involving mitochondrial dysfunction and OS, but [Ca²⁺]ᵢ fluctuation and GJ injury were only observed with BaP-induced reproductive toxicity. The male reproductive toxicity of the selected PAHs was ranked in the order of BaP > Py > Fl > Phe.
اظهر المزيد [+] اقل [-]Long-term exposure to environmental levels of phenanthrene induces emaciation-thirst disease-like syndromes in female mice
2022
Fang, Lu | Ou, Kunlin | Huang, Jie | Zhang, Shenli | Zhang, Ying | Zhao, Hezhen | Chen, Meng | Wang, Chonggang
Phenanthrene (Phe) is a polycyclic aromatic hydrocarbon widely present in foods and drinking water. To explore the detrimental effects of Phe on body metabolism, female Kunming mice were treated with Phe in drinking water at concentrations of 0.05, 0.5 and 5 ng/mL. After exposure for 270 d, the animals exhibited dose-dependent reduced body weight and increased water consumption. The dose-dependent accumulation of Phe in the brain decreased hypothalamic neuron numbers, upregulated hypothalamic expression of anaplastic lymphoma kinase, elevated norepinephrine levels in white adipose tissue (WAT) and further activated lipolysis in WAT, leading to a reduction in fat mass. Brown adipose tissue formation was reduced, accompanied by the inhibition of the bone morphogenetic protein signaling pathway. A simultaneous reduced serum levels of antidiuretic hormone (arginine vasopressin) might be one of the reasons for increased water consumption. The present results indicate an environmental etiology and prevention way for the development of emaciation-thirst disease.
اظهر المزيد [+] اقل [-]Urban fine particulate matter causes cardiac hypertrophy through calcium-mediated mitochondrial bioenergetics dysfunction in mice hearts and human cardiomyocytes
2022
Zou, Lingyue | Li, Binjing | Xiong, Lilin | Wang, Yan | Xie, Wenjing | Huang, Xiaoquan | Liang, Ying | Wei, Tingting | Liu, Na | Chang, Xiaoru | Bai, Changcun | Wu, Tianshu | Xue, Yuying | Zhang, Ting | Tang, Meng
In recent years, the cardiovascular toxicity of urban fine particulate matter (PM₂.₅) has sparked significant alarm. Mitochondria produce 90% of ATP and make up 30% of the volume of cardiomyocytes. Thus knowledge of myocardial mitochondrial dysfunction due to PM₂.₅ exposure is essential for further cardiotoxic effects. Here, the mechanism of PM₂.₅-induced cardiac hypertrophy through calcium overload and mitochondrial dysfunction was investigated in vivo and in vitro. Male and female BALB/c mice were given 1.28, 5.5, and 11 mg PM₂.₅/kg bodyweight weekly through oropharyngeal inhalation for four weeks and were assigned to low, medium, and high dose groups, respectively. PM₂.₅-induced myocardial edema and cardiac hypertrophy were detected in the high-dose group. Mitochondria were scattered and ruptured with abnormal ultrastructural morphology. In vitro experiments on human cardiomyocyte AC16 showed that exposure to PM₂.₅ for 24 h caused opened mitochondrial permeability transition pore --leading to excessive calcium production, decreased mitochondrial membrane potential, weakened mitochondrial respiratory metabolism capacity, and decreased ATP production. Nevertheless, the administration of calcium chelator ameliorated the mitochondrial damage in the PM₂.₅-treated group. Our in vivo and in vitro results confirmed that calcium overload under PM₂.₅ exposure triggered mTOR/AKT/GSK-3β activation, leading to mitochondrial bioenergetics dysfunction and cardiac hypertrophy.
اظهر المزيد [+] اقل [-]Potentials of orally supplemented selenium-enriched Lacticaseibacillus rhamnosus to mitigate the lead induced liver and intestinal tract injury
2022
Jin, Han | Riaz Rajoka, Muhammad Shahid | Xu, Xiaoguang | Liao, Ning | Pang, Bing | Yan, Lu | Liu, Guanwen | Sun, Hui | Jiang, Chunmei | Shao, Dongyan | Barba, Francisco J. | Shi, Junling
Lead is a metal that exists naturally in the Earth's crust and is a ubiquitous environmental contaminant. The alleviation of lead toxicity is important to keep human health under lead exposure. Biosynthesized selenium nanoparticle (SeNPs) and selenium-enriched Lactobacillus rhamnosus SHA113 (Se-LRS) were developed in this study, and their potentials in alleviating lead-induced injury to the liver and intestinal tract were evaluated in mice by oral administration for 4 weeks. As results, oral intake of lead acetate (150 mg/kg body weight per day) caused more than 50 times and 100 times lead accumulation in blood and the liver, respectively. Liver function was seriously damaged by the lead exposure, which is indicated as the significantly increased lipid accumulation in the liver, enhanced markers of liver function injury in serum, and occurrence of oxidative stress in liver tissues. Serious injury in intestinal tract was also found under lead exposure, as shown by the decrease of intestinal microbiota diversity and occurrence of oxidative stress. Except the lead content in blood and the liver were lowered by 52% and 58%, respectively, oral administration of Se-LRS protected all the other lead-induced injury markers to the normal level. By the comparison with the effects of normal L. rhamnosus SHA113 and the SeNPs isolated from Se-LRS, high protective effects of Se-LRS can be explained as the extremely high efficiency to promote lead excretion via feces by forming insoluble mixture. These findings illustrate the developed selenium-enriched L. rhamnosus can efficiently protect the liver and intestinal tract from injury by lead.
اظهر المزيد [+] اقل [-]Pesticides in a warmer world: Effects of glyphosate and warming across insect life stages
2022
Stahlschmidt, Z.R. | Whitlock, J. | Vo, C. | Evalen, P. | D, Bui
Glyphosate (GLY) is a broad-spectrum herbicide that is the most commonly applied pesticide in terrestrial ecosystems in the U.S. and, potentially, worldwide. However, the combined effects of warming associated with climate change and exposure to GLY and GLY-based formulations (GBFs) on terrestrial animals are poorly understood. Animals progress through several life stages (e.g., embryonic, larval, and juvenile stages) that may exhibit different sensitivities to stressors. Therefore, we factorially manipulated temperature and GLY/GBF exposure in the variable field cricket (Gryllus lineaticeps) during two life stages—nymphal development and adulthood—and examined key animal traits, such as developmental rate, body size, food consumption, reproductive investment, and lifespan. A thermal environment simulating future climate warming obligated several costs to fitness-related traits. For example, warming experienced during nymphal development reduced survival, adult body mass and size, and investment into flight capacity and reproduction. Warming experienced by adults reduced lifespan and growth rate. Alternatively, the effects of GBF exposure were more subtle, often context-dependent (e.g., effects were only detected in one sex or temperature regime), and were stronger during adult exposure relative to exposure during development. There was evidence of additive costs of warming and GBF exposure to rates of feeding and growth in adults. Yet, the negative effect of GBF exposure to adult lifespan did not occur in warming conditions, suggesting that ongoing climate change may obscure some of the costs of GBFs to non-target organisms. The effects of GLY alone (i.e., in the absence of proprietary surfactants found in commercial formulations) were non-existent. Animals will be increasingly exposed to warming and GBFs, and our results indicate that GBF exposure and warming can entail additive costs for an animal taxon (insects) that plays critical roles in terrestrial ecosystems.
اظهر المزيد [+] اقل [-]Perfluorooctane sulfonate induces suppression of testosterone biosynthesis via Sertoli cell-derived exosomal/miR-9-3p downregulating StAR expression in Leydig cells
2022
Huang, Jiyan | Ren, Hang | Tan, Annie | Li, Ting | Wang, Hongxia | Jiang, Lianlian | Zheng, Shaokai | Qi, Han | Ji, Binyan | Wang, Xipei | Qu, Jianhua | Zhao, Jianya | Qiu, Lianglin
Perfluorooctane sulfonate (PFOS) is associated with male reproductive disorder, but the related mechanisms are still unclear. In this study, we used in vivo and in vitro models to explore the role of Sertoli cell-derived exosomes (SC-Exo)/miR-9-3p/StAR signaling pathway on PFOS-induced suppression of testosterone biosynthesis. Forty male ICR mice were orally administrated PFOS (0.5–10 mg/kg/bw) for 4 weeks. Bodyweight, organ index, sperm count, reproductive hormones were evaluated. Primary Sertoli cells and Leydig cells were used to delineate the molecular mechanisms that mediate the effects of PFOS on testosterone biosynthesis. Our results demonstrated that PFOS dose-dependently induced a decrease in sperm count, low levels of testosterone, and damage in testicular interstitium morphology. In vitro models, PFOS significantly increased miR-9-3p levels in Sertoli cells and SC-Exo, accompanied by a decrease in testosterone secretion and StAR expression in Leydig cells when Leydig cells were exposed to SC-Exo. Meanwhile, inhibition of SC-Exo or miR-9-3p by their inhibitors significantly rescued PFOS-induced decreases in testosterone secretion and the mRNA and protein expression of the StAR gene in Leydig cells. In summary, the present study highlights the role of the SC-Exo/miR-9-3p/StAR signaling pathway in PFOS-induced suppression of testosterone biosynthesis, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders.
اظهر المزيد [+] اقل [-]MiR-34a/Sirt1/p53 signaling pathway contributes to cadmium-induced nephrotoxicity: A preclinical study in mice
2021
Hao, Rili | Song, Xinyu | Sun-Waterhouse, Dongxiao | Tan, Xintong | Li, Feng | Li, Dapeng
Cadmium (Cd), as an environmental pollutant, can lead to nephrotoxicity. However, its nephrotoxicological mechanisms have not been fully elucidated. In this study, Cd (1.5 mg/kg body weight, gavaged for 4 weeks) was found to induce the renal damage in mice, based on indicators including Cd concentration, kidney index, serum creatinine and blood urea nitrogen levels, pro-inflammatory cytokines and their mRNA expressions, levels of Bcl-2, Bax and caspase9, and histopathological changes of the kidneys. Furthermore, Cd-caused detrimental changes through inducing inflammation and apoptosis via the miR-34a/Sirt1/p53 axis. This is the first report on the role of miR-34a/Sirt1/p53 axis in regulating Cd-caused apoptosis and nephrotoxicity in mice. The findings obtained in this study provide new insights into miRNA-based regulation of heavy metal induced-nephrotoxicity.
اظهر المزيد [+] اقل [-]Environmental exposure to cadmium reduces the primary antibody-mediated response of wood mice (Apodemus sylvaticus) from differentially polluted locations in the Netherlands
2021
García-Mendoza, Diego | van den Berg, Hans J.H.J. | Brink, Nico W. van den
The Wood mouse (Apodemus sylvaticus) is a widespread mammalian species that acts as a reservoir host for multiple infections, including zoonotic diseases. Exposure to immunotoxins, like for instance trace metals, may reduce the ability of the host to mount proper responses to pathogens, potentially increasing the transmission and prevalence of infections. Antibody-mediated responses are crucial in preventing and limiting infections, and the quantification of the primary antibody response is considered a sensitive predictor of immunosuppression. The current study aims to investigate effects of cadmium exposure on the antibody-mediated responses of wood mice inhabiting polluted and non-polluted areas in the Netherlands. Wood mice were captured alive at different locations and immunized to sheep red blood cells (SRBC) to induce a primary antibody response. SRBC-specific antibody-producing cells, or plaque forming cells (PFC), were quantified and related to kidney cadmium levels. Differential circulating main leukocyte populations were also characterised. Cadmium concentrations in mice kidneys differed between mice captured at different locations, and increased with individual body mass, likely associated with age-related time of exposure. Effect of cadmium was apparent on the percentages of B cell counts in blood. Because of potential natural immune heterogeneity between wild rodent populations, mice immune responses were analysed and compared grouped by captured locations. Capture location had significant effect on the total counts of white blood cells. Increasing cadmium exposure in wood mice captured from polluted sites was associated with a decrease of splenic PFC counts. This field research shows that wood mice antibody responses can be impaired by cadmium exposure, even at low environmental levels, by affecting B cell functioning mainly. Impaired B cell function can make exposed mice more susceptible to infections, potentially increasing the reservoir function of their populations. It also shows that immunomodulatory effects in the field should be assessed site specifically.
اظهر المزيد [+] اقل [-]Modeling the fate and human health impacts of pharmaceuticals and personal care products in reclaimed wastewater irrigation for agriculture
2021
Shahriar, Abrar | Tan, Junwei | Sharma, Priyamvada | Hanigan, David | Verburg, Paul | Pagilla, Krishna | Yang, Yu
Wastewater reclamation and reuse for agriculture have attracted a great deal of interest, due to water stress caused by rapid increase in human population and agricultural water demand as well as climate change. However, the application of treated wastewater for irrigation can lead to the accumulation of pharmaceuticals and personal care products (PPCPs) in the agricultural crops, grazing animals, and consequently to human dietary exposure. In this study, a model was developed to simulate the fate of five PPCPs; triclosan (TCS), carbamazepine (CBZ), naproxen (NPX), gemfibrozil (GFB), and fluoxetine (FXT) during wastewater reuse for agriculture, and potential human dietary exposure and health risk. In a reclaimed wastewater-irrigated grazing farm growing alfalfa, it took 100–535 days for PPCPs to achieve the steady-state concentrations of 1.43 × 10⁻⁶, 4.73 × 10⁻⁵, 1.17 × 10⁻⁶, 1.53 × 10⁻⁵, and 7.38 × 10⁻⁶ mg/kg for TCS, CBZ, NPX, GFB, and FXT in soils, respectively. The accumulated concentration of PPCPs in the plant (alfalfa) and grazing animals (beef) ranged 2.86 × 10⁻⁷− 4.02 × 10⁻³ and 4.39 × 10⁻¹⁵− 6.27 × 10⁻⁷ mg/kg, respectively. Human dietary exposure to these compounds through beef consumption was calculated to be 1.67 × 10⁻¹⁸− 1.74 × 10⁻¹⁰ mg/kg bodyweight/d, much lower than the acceptable daily intake (ADI). Similar results were obtained for a ‘typical’ reclaimed wastewater irrigated farm based on the typical setup using our model. Screening analysis showed that PPCPs with relatively high LogD value and lower ratios of degradation rate (in soils) to plant uptake have a greater potential to be transferred to humans and cause potential health risks. We established a modeling method for evaluating the fate and human health effects of PPCPs in reclaimed wastewater reuse for the agricultural system and developed an index for screening PPCPs with high potential to accumulate in agricultural products. The model and findings are valuable for managing water reuse for irrigation and mitigating the harmful effects of PPCPs.
اظهر المزيد [+] اقل [-]Consumption of field-realistic doses of a widely used mito-toxic fungicide reduces thorax mass but does not negatively impact flight capacities of the honey bee (Apis mellifera)
2021
Glass, Jordan R. | Fisher, Adrian | Fewell, Jennifer H. | DeGrandi-Hoffman, Gloria | Ozturk, Cahit | Harrison, Jon F.
Commercial beekeepers in many locations are experiencing increased annual colony losses of honey bees (Apis mellifera), but the causes, including the role of agrochemicals in colony losses, remain unclear. In this study, we investigated the effects of chronic consumption of pollen containing a widely-used fungicide (Pristine®), known to inhibit bee mitochondria in vitro, which has recently been shown to reduce honey bee worker lifespan when field-colonies are provided with pollen containing field-realistic levels of Pristine®. We fed field colonies pollen with a field-realistic concentration of Pristine® (2.3 ppm) and a concentration two orders of magnitude higher (230 ppm). To challenge flight behavior and elicit near-maximal metabolic rate, we measured flight quality and metabolic rates of bees in two lower-than-normal air densities. Chronic consumption of 230 but not 2.3 ppm Pristine® reduced maximal flight performance and metabolic rates, suggesting that the observed decrease in lifespans of workers reared on field-realistic doses of Pristine®-laced pollen is not due to inhibition of flight muscle mitochondria. However, consumption of either the 230 or 2.3 ppm dose reduced thorax mass (but not body mass), providing the first evidence of morphological effects of Pristine®, and supporting the hypothesis that Pristine® reduces forager longevity by negatively impacting digestive or nutritional processes.
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