Cadmium Exposure Research Articles

Investigating the effects of three trace metals on the viability, embryonic development, and locomotor behavior of the Seminole ramshorn snail at environmentally relevant concentrations.

Trace metal contamination is a widespread issue due to its many natural and anthropogenic sources and known carcinogenic, teratogenic, and reproductive effects. As previous invertebrate trace metal research has primarily focused on model species (Daphnia magna, Chironomidae, etc.), our understanding of effects on non-model invertebrate species remains relatively poor. As such, this study assessed the exposure effects of cadmium, arsenic, and lead on viability, locomotor behavior, and embryonic development of the Seminole ramshorn snail (Planorbella duryi). Exposure treatments of CdCl2 , Na2 HAsO4 • 7H2 O, or Pb (NO3 )2 were prepared at concentrations of 0, 0.01, 0.1, 1, and 10mg/L and confirmed using inductively coupled plasma optical emission spectroscopy (ICP-OES). Individual adult P.duryi were exposed for 7 days with viability assessed every 24 h, and locomotor behavior was accessed on Days 1 and 7 using ToxTrac v2.97 automated behavior software. Individual embryos from newly laid (<6h old) embryonic clutches were exposed for 10days, during which embryonic development stage was documented every 24 h. Based on our results, an additional follow-up study for cadmium was conducted using a lower range of 0-0.1mg/L to allow for the observation of sublethal endpoints. Adult lead and cadmium exposure resulted in significant mortality in the highest treatments (1 and 10mg/L), dose-dependent behavioral effects, and delayed embryonic development. Arsenic exposures resulted in little to no impacts for all assessed endpoints. Our results provide new insight into the sublethal impacts of these contaminants and highlight potential for behavior and embryonic development as useful tools for risk assessment. PRACTITIONER POINTS: The exposure effects of lead, cadmium, and arsenic on the viability, embryonic development, and locomotor behavior of a common freshwater snail species was investigated using environmentally relevant concentrations. The severity of impact differed for each trace metal, with cadmium being the most toxic and arsenic the least toxic at concentrations ranging from 0 to 10 mg/L. Embryonic development appeared to be the most sensitive endpoint of those tested in this study, suggesting that exposure may have prolonged effects that extend to population and community levels. The Seminole ramshorn snail serves as a sensitive alternative model species that can be used to assess the impacts of contaminants on freshwater invertebrates in future studies.

Cadmium exposure induces pyroptosis of TM4 cells through oxidative stress damage and inflammasome activation

Cadmium (Cd) is a harmful metal that seriously affects the male reproductive system, but the mechanism of how Cd exposure damages Sertoli cells is not fully understood. This study used TM4 cells to explore the mechanism of Cd damage to Sertoli cells. We found that Cd was concentration- and time-dependent on TM4 cell viability. Cd exposure increased intracellular reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH), and Interleukin-1β (IL-1β) release in TM4 cells, decreased mitochondrial function, and increased pyroptosis. N-acetylcysteine (NAC), MCC950 and BAY 11–7082 (BAY) alleviate the release of IL-1β and LDH induced by Cd. NAC reduced Cd induced increases in ROS, NLRP3, Caspase-1, Heme oxygenase-1(HO-1), superoxide dismutase (SOD2), and increased mitochondrial function. The activation of GSDMD is the main causes of pyroptosis, and NAC significantly inhibit its activation and formation. Our results suggest that Cd exposure induces a toxic mechanism of GSDMD-mediated pyroptosis in TM4 cells by increasing ROS levels and activating the inflammasome.

Dietary exposure of cadmium from milk products containing cocoa in children aged 1 to 5 years old, pregnant and lactating women

This study was conducted to evaluate the cadmium contamination level in milk products containing cocoa (chocolate flavour milk products), and its dietary exposure in vulnerable consumers, i.e. children aged one to five years old, pregnant and lactating women (PLW) in Indonesia. A total of 78 samples of milk products, which were registered in the Indonesian National Agency of Drug and Food Control (NADFC) and distributed in the Indonesian market, were analysed using Atomic Absorption Spectrophotometry Graphite Furnace (AAS-GF). Milk powder for children aged one to five years, UHT liquid milk, and condensed milk meet the NADFC regulation No. 5 of 2018. However, 63% of chocolate flavour PLW milk powder had Cd levels that exceeded the NADFC (maximum 10 µg/kg). Chocolate flavour milk has a higher Cd level than non-chocolate flavour milk products. The highest value of Cd exposure was in children aged three to five years old who consumed chocolate flavour milk powder, with an average value of 0.095 and P95 value of 0.151 µg/kg BW/day. However, based on the P95 exposure value, the contribution of Cd exposure for this product was only 18.12 and 42.27% to the PTMIJECFA and TWI-EFSA values, therefore, it was not considered a risk of health problems. For PLW milk powder, although 63% of samples exceeded the NADFC regulation, the P95 value of Cd exposure was 1.41 and 3.29% to the PTMI and TWI value, therefore, it was also considered not to pose a risk of health problems.

Cadmium-induced Carcinogenesis in Respiratory Organs and the Prostate: Insights from Three Perspectives on Toxicogenomic Approach.

Cadmium (Cd) exposure primarily occurs through inhalation, either by smoking or occupational exposure to contaminated air. Upon inhalation, Cd ultimately reaches the prostate through the bloodstream. In this review, we investigate the carcinogenic potential of Cd in both respiratory organs and the prostate. Specifically, this review examines cellular metabolism, comprehensive toxicity, and carcinogenic mechanisms by exploring gene ontology, biological networks, and adverse outcome pathways. In the respiratory organs, Cd induces lung cancer by altering the expression of IL1B and FGF2, causing DNA damage, reducing cell junction integrity, and promoting apoptosis. In the prostate, Cd induces prostate cancer by modifying the expression of EDN1 and HMOX1, leading to abnormal protein activities and maturation, suppressing tumor suppressors, and inducing apoptosis. Collectively, this review provides a comprehensive understanding of the carcinogenic mechanisms of Cd in two different organs by adopting toxicogenomic approaches. These insights can serve as a foundation for further research on cadmium-induced cancer, contributing to the establishment of future cancer prevention strategies.

Effect of Cadmium Toxicity on Different Antioxidant Enzymes in Growing Wheat (Triticum aestivum L.) Seedlings

Assessing the impact of Cadmium (Cd) on plant cells requires an understanding of the defensive mechanisms and adaptive responses employed by plants to counteract the deleterious effects of Cd toxicity. Wheat seedlings were grown under different concentrations (0 µM, 100 µM and 500 µM) of Cadmium salt (CdCl2). The growth of metal-treated seedlings was significantly affected. This study evaluated the ecotoxicological effects of two experimental concentrations of Cadmium (100 µM and 500 µM) against water control. It has been examined in recent studies that the toxic effects of Cadmium comprising the variables in fresh weight, dry weight and germination percentage of the wheat seedlings, photosynthesis and enzymatic activities in different stresses after seven days of cadmium exposure on roots and shoots of wheat seedling. Different antioxidant enzyme activities such as catalase (CAT), ascorbic acid oxidase (AOX), catechol peroxidase (CPX), superoxide dismutase (SOD), acid and alkaline phosphatase and inorganic pyrophosphatase have been measured. The various enzyme activities were increased in roots treated with high concentrations (500 µM) of Cadmium but decreased at low concentrations (100 µM) with respect to water control. This result indicated a complex defense mechanism in the root tissues induced by Cadmium. This work provides valuable insights for future research on plant responses to heavy metal stress and advances our understanding of the complex relationship between Cd toxicity and the antioxidant defense system in wheat seedlings.

Occupational carcinogens in Italy: an overview on exposure to cadmium and its compounds.

Given the recognized carcinogenicity of cadmium, several regulatory interventions have been carried out over the years to protect exposed workers. The aim of the study is to investigate the prevalence and extent of exposure to cadmium among Italian workers. Data was collected from a nation-wide occupational exposure registry (SIREP, 1996-2022). Gender-specific statistical analysis was carried out for some exposure-related variables (cadmium compound, activity sector, occupational group, firm size). Potentially exposed workers were estimated for some industrial sectors. Concurrent exposures were investigated using cluster analysis. Overall 4,264 measurements were analyzed. Four industrial sectors were found to be most involved by cadmium exposure: base metal manufacturing, fabricated metal products, machinery and equipment, and other transport equipment (55% of measurements). Jewellery/precious-metal workers, and glass/ceramic plant operators were found to be most at exposure risk. A total of 26,470 workers potentially exposed was estimated (69% men). Concurrent exposures to other occupational carcinogens were detected quite frequently (52% of workers). Several situations of exposure and co-exposure to cadmium deserve attention and awareness in order to minimize the risks associated with workers' health. Recognition of potentially hazardous exposure conditions is an important step in prevention strategies to better protect workers against cancer-causing agents.

Cadmium exposure and thyroid hormone disruption: a systematic review and meta-analysis.

This meta-analysis aimed to analyze the effect of cadmium (Cd) exposure on thyroid hormone disruption. Databases including PubMed, Embase, Cochrane Library, and Scopus were searched for studies published up to December 14, 2022. Studies evaluating the association between Cd exposure (blood Cd [BCd] or urine Cd [UCd]) and thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [FT4], total triiodothyronine [TT3]) or thyroid autoimmunity (thyroglobulin antibody [TgAb] or thyroperoxidase Ab [TPOAb]) were included. This systematic review included 12 cross-sectional studies. Cd exposure showed a neutral association with TSH (pooled correlation=0.016, 95 % confidence interval [CI]=-0.013 to 0.045, p=0.277), FT4 (pooled correlation=0.028, 95 % CI=-0.005 to 0.061, p=0.098), and thyroid autoimmunity (pooled odds ratio=1.143, 95 % CI=0.820-1.591, p=0.430). However, Cd exposure showed a positive association with TT3 (pooled correlation=0.065, 95 % CI=0.050-0.080, p<0.001), which was consistent with the BCd and UCd subgroup analyses (pooled correlation=0.053 and 0.081, respectively, both p<0.001). Cd exposure was not associated with TSH, FT4, or thyroid autoimmunity but tended to increase with TT3.

Juggling cadmium detoxification and zinc homeostasis: A division of labour between the two C. elegans metallothioneins

The chemical properties of toxic cadmium and essential zinc are very similar, and organisms require intricate mechanisms that drive selective handling of metals. Previously regarded as unspecific “metal sponges”, metallothioneins (MTLs) are emerging as metal selectivity filters. By utilizing C. elegans mtl-1 and mtl-2 knockout strains, metal accumulation in single worms, single copy fluorescent-tagged transgenes, isoform specific qPCR and lifespan studies it was possible to demonstrate that the handling of cadmium and zinc by the two C. elegans metallothioneins differs fundamentally: the MTL-2 protein can handle both zinc and cadmium, but when it becomes unavailable, either via a knockout or by elevated cadmium exposure, MTL-1 takes over zinc handling, leaving MTL-2 to sequester cadmium. This division of labour is reflected in the folding behaviour of the proteins: MTL-1 folded well in presence of zinc but not cadmium, the reverse was the case for MTL-2. These differences are in part mediated by a zinc-specific mononuclear His3Cys site in the C-terminal insertion of MTL-1; its removal affected the entire C-terminal domain and may shift its metal selectivity towards zinc. Overall, we uncover how metallothionein isoform-specific responses and protein properties allow C. elegans to differentiate between toxic cadmium and essential zinc.

Higher temperature and humidity exacerbate pollutant-associated lung dysfunction in the elderly

RationaleAir pollution and extreme temperature and humidity are risk factors for lung dysfunction, but their interactions are not clearly understood. ObjectivesTo assess the impact of exposure to air pollutants and meteorological factors on lung function, and the contribution of their interaction to the overall effect. MethodsThe peak expiratory flow rates of 135 participants were repeatedly measured during up to four visits. Two weeks before each visit, the concentrations of gaseous pollutants and 19 fine particle components, and the temperature and relative humidity, were continuously monitored in the community where they lived. A Bayesian Kernel machine regression model was used to explore the non-linear exposure-response relationships of the peak expiratory flow rate with pollutant exposure and meteorological factors, and their interactions. Measurements and main resultsIncreased temperature and relative humidity could exacerbate pollutant-associated decline in the peak expiratory flow rate, although their associations with lung dysfunction disappeared after adjustment for pollutant exposure. For example, declines of peak expiratory flow rate associated with interquartile range increase of 3-day cadmium exposure were −0.03 and −0.07 units, when temperature was at 0.1 and 19.5 °C, respectively. Decreased temperature were associated with declines of peak expiratory flow rate after adjustment for pollutant exposure, and had interaction with pollutant exposure on lung dysfunction. ConclusionsHigh temperature, low temperature, and high humidity were all high-risk factors for lung dysfunction, and their interactions with pollutant levels contributed greatly to the overall effects.

Toxicity and detoxication assessment of juvenile black seabream (Acanthopagrus schlegelii) in response to dietary cadmium exposure: Based on growth performance and stress indicators

Cadmium (Cd) is a major pollutant in water, and long-term Cd exposure seriously threatens aquatic organisms. This study evaluated the effects of dietary Cd on growth performance, tissue Cd accumulation, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, apoptosis, and anti-stress response in juvenile black seabream (Acanthopagrus schlegelii). Six experimental diets containing different concentration of Cd were formulated: 0.02 (Control, Cd0.02), 1.60 (Cd1.60), 24.29 (Cd24.29), 49.04 (Cd49.04), 117.26 (Cd 117.26), and 289.65 (Cd289.65) mg/kg. A feeding experiment was performed on 540 juvenile black seabreams (initial weight, 1.42 ± 0.01 g), which were conducted for ten weeks. The findings revealed that Cd in the diet lowered weight gain (WG) and specific growth rate (SGR), but had no effect on survival. Dramatically positive linear trends were found between increasing dietary Cd contents and tissue Cd accumulation, including liver, kidney, and muscle. Dietary Cd exposure increased malondialdehyde (MDA) production in both serum and liver, hence, caused oxidative stress. The endoplasmic reticulum (ER) stress-related genes, including grp78, atf6, and xbp1, were markedly increased with increased dietary Cd levels, showing ER stress was triggered. Likewise, transcriptional expression levels of genes related to anti-stress response mt2, hsp70, and hsp90 were linearly up-regulated with increased dietary Cd contents. Regarding apoptosis, the transcriptional expression levels of pro-apoptosis genes caspase7, caspase9, and bax and anti-apoptosis gene bcl-2 were all significantly promoted with the increasing dietary Cd levels. Similar patterns were found for gene expression levels linked to inflammatory response, as the dietary Cd contents increased, nuclear transcription factor nf-κb, pro-inflammatory cytokines tnfα and il-1β, and anti-inflammatory il-10 and tgfβ were dramatically elevated. In conclusion, dietary Cd supplementation suppressed growth performance, increased Cd deposition in tissues, induced oxidative stress, ER stress, apoptosis, and inflammation. In contrast, black seabream juveniles also showed substantial tolerance for dietary Cd exposure by promoting anti-stress ability.

Assessment of long-term dietary cadmium exposure in children in Germany: Does consideration of data from total diet studies reduce uncertainties from food monitoring programmes?

Total diet studies (TDS) and food monitoring programmes are different approaches for collecting occurrence data on substances in food. This case study evaluated the practical applicability of TDS data (BfR MEAL Study) and monitoring data for the assessment of long-term cadmium exposure in children in Germany. Cadmium data from both programmes were combined with food consumption data from the KiESEL study. Uncertainties associated with both assessments were systematically described. Using monitoring data resulted in cadmium intakes approximately 3 times higher than the use of BfR MEAL Study data. Incomplete data and neglect of market shares and consumption weights were considered by conservative data adjustments to the monitoring data and mainly explain the higher estimates. Fewer data adjustments were necessary for BfR MEAL Study data, which covered almost the entire diet and considered consumer behaviour during sample collection and sample preparation. In sum, the use of the BfR MEAL Study data resulted in less uncertainty and more reliable exposure estimates for chronic assessments over the entire diet. However, description of variability and upper tails of substance distributions in food remain essential features of monitoring data. The integration of both programmes into a complementary system further improves food safety.

Cadmium exposure of heavy metal-tolerant Mesembryanthemum crystallinum L. (the common ice plant) stimulates gas exchange

Cadmium exposure of heavy metal-tolerant Mesembryanthemum crystallinum L. (the common ice plant) stimulates gas exchange

Prenatal exposure to environmental heavy metals and newborn telomere length: A systematic review and meta-analysis

Exposure to environmental heavy metals is associated with telomere length (TL) alteration. Available information regarding the effect of prenatal exposure to environmental pollutants on newborn TL is controversial. The aim of this study is to systematically review and conduct a meta-analysis of the existing epidemiological studies on the associations between prenatal metal exposure and newborn TL. A comprehensive literature search was performed using the online databases of PubMed, Web of Science, and ScienceDirect from their inception to December 1, 2023. Thirteen eligible studies were included from the overall initial identification of 3559 records. The effect size was expressed as standardized beta coefficients with 95% confidence intervals (CIs) by the restricted maximum-likelihood approach with a weighted random-effects model. Prenatal exposure to environmental heavy metals was associated with a shorter newborn TL (standardized beta = −0.04; 95% CI: −0.08, 0.00; p = 0.05). Subgroup analysis showed that prenatal exposure to cadmium was significantly, negatively associated with TL in newborns (standardized beta = −0.05; 95% CI: −0.10, −0.01; p = 0.021). Heavy metal exposure during the third trimester was significantly associated with a shorter TL in newborns (standardized beta = −0.05; 95% CI: −0.11, −0.01; p = 0.045). No significant association was found between the newborn's sex and exposure sample type. This study provides evidence for the negative effect of prenatal exposure to heavy metals on newborn TL. In particular, cadmium exposure and exposure during the third trimester of pregnancy are critical factors associated with heavy metal-induced TL shortening.

Cadmium exposure experiments on calanoid copepods reveal significant shortfall in water quality criteria for managing coastal marine ecosystems in West Africa

Cadmium exposure experiments on calanoid copepods reveal significant shortfall in water quality criteria for managing coastal marine ecosystems in West Africa

Environmental Cadmium Exposure Exacerbated Bone Loss in NAFLD Mice.

Due to rapid urbanization and industrialization, Cadmium (Cd) contamination is widespread. Meanwhile, the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. Cd is linked to bone damage. However, the osteotoxicity of environmental Cd exposure in NAFLD remains unclear. Therefore, this study aimed to investigate the effects and potential mechanisms of Cd on bone metabolism in NAFLD mice. NAFLD mice were treated with 50mg/L cadmium chloride in drinking water for 12 weeks. Bone microstructures were scanned by Micro-CT. Liver lipid droplets and fibrosis were measured by histopathological staining. Insulin tolerance tests were performed in mice. RT-PCR and Western blot were performed to analyse hepatic inflammation factors. Results show no damage in healthy mice exposed to Cd. However, Cd exacerbated liver fibrosis and significantly reduced cancellous bone mineral density and decreased the number and thickness of trabecular bone in NAFLD mice. Additionally, the morphology of trabecular bone transformed from a plate structure to a rod structure in NAFLD mice after Cd exposure. The underlying mechanism appears to be related to the Cd-induced direct or indirect toxicity. Exacerbated liver fibrosis, increased inflammatory factors (TGF-β and IL-1β), and reduced lecithin-cholesterol acyltransferase (LCAT) and insulin-like growth factor-1 (IGF-1) might contribute to bone damages. Collectively, our study illustrates that despite lower dosing Cd exposure did not induce bone damages in healthy mice, Cd caused bone loss in NAFLD mice. Therefore, it is recommended that individuals with metabolic disorders should avoid working in Cd pollution environment and consuming cadmium-contaminated food and water.

Cadmium-induced global DNA hypermethylation promoting mitochondrial dynamics dysregulation in hippocampal neurons.

Environmental cadmium exposure during pregnancy or adolescence can cause neurodevelopmental toxicity, lead to neurological impairment, and reduce cognitive abilities, such as learning and memory. However, the mechanisms by which cadmium causes neurodevelopmental toxicity and cognitive impairment are still not fully elucidated. This study used hippocampal neurons cultured in vitro to observe the impact of cadmium exposure on mitochondrial dynamics and apoptosis. Exposure to 5 μM cadmium causes degradation of hippocampal neuron cell bodies and axons, morphological destruction, low cell viability, and apoptosis increase. Cadmium exposure upregulates the expression of mitochondrial fission proteins Drp1 and Fis1, reduces the expression of mitochondrial fusion-related proteins MFN1, MFN2, and OPA1, as well as reduces the expression of PGC-1a. Mitochondrial morphology detection demonstrated that cadmium exposure changes the morphological structure of mitochondria in hippocampal neurons, increasing the number of punctate and granular mitochondria, reducing the number of tubular and reticular mitochondria, decreasing mitochondrial mass, dissipating mitochondrial membrane potential (ΔΨm), and reducing adenosine triphosphate (ATP) production. Cadmium exposure increases the global methylation level of the genome and upregulates the expression of DNMT1 and DNMT3α in hippocampal neurons. 5-Aza-CdR reduces cadmium-induced genome methylation levels in hippocampal neurons, increases the number of tubular and reticular mitochondria, and promotes cell viability. In conclusion, cadmium regulates the expression of mitochondrial dynamics-related proteins by increasing hippocampal neuron genome methylation, changing mitochondrial morphology and function, and exerting neurotoxic effects.

Distribution and accumulation of Cadmium in different trophic levels affecting Serangium japonicum, the predatory beetle of whitefly Bemisia tabaci, biologically, physiologically and genetically: An experimental study

Cadmium (Cd) is a heavy metal that is of great concern in agroecosystems due to its toxicity to plants, herbivores, carnivores, and human beings. The current study evaluated the allocation and bioaccumulation of Cd from soil to cotton plants, cotton plants to herbivore pests, and herbivorous pests to a natural enemy predator. When soil was spiked with 100 mg/kg Cd, results demonstrated that cotton roots accumulated more Cd than the stems and leaves. The bioaccumulation of Cd was less in 4th instar larvae, pupa, and adults of Serangium japonicum than in Bemisia tabaci adults. The bioaccumulation in S. japonicum elongated the immature development period and reduced adult longevity, oviposition days, fertility, and total pre-oviposition duration. The net reproduction of S. japonicum was also reduced, as was female mature weight and feeding potential; as a result, Cd exposure could reduce the future population size compared to uncontaminated populations. There was decreased activity of the antioxidant enzymes (SOD, CAT, and POD) and energy-conserving lipids (glycogen, triglyceride, and total cholesterol) in Cd-contaminated S. japonicum compared to controls. The detoxifying enzyme activity of GST and P450 increased while AChE activity did not change. The qRT-PCR research showed that SOD1, CAT, POD, glycogen, and triglyceride gene expression was higher than in controls, whereas detoxification gene expression did not change. Our results indicate that Cd exposure has a physiological trade-off between its adverse effects on life history traits and elevated detoxification and antioxidation of S. japonicum, which could result from gene expression alteration. Further studies are needed to assess whether Cd exposure causes irreversible DNA damage in S. japonicum.

Effects of cadmium exposure on tissue structure, antioxidant enzyme activity, serum biochemical indices and gene expression in the liver of juvenile largemouth bass (Micropterus salmoides)

This study aimed to understand the effect of various levels of waterborne cadmium exposure and associated integrated response in largemouth bass (Micropterus salmoides). The experimental fish were randomly divided into 4 groups: Group H (high concentration group): 0.25 mg/L of water (100% of the LC50); Group M (medium concentration group): 0.01 mg/L of water (50% of the LC50); group L (low concentration group): 0.05 mg/L of water (12.5% of the LC50) and group C (control). Experimental fish in group C (control group) were cultured in cadmium (Cd)-free tap water. After 28 days of Cd exposure, the gill and liver tissues were collected for histological analysis and antioxidant enzyme activities assay. Serum biochemical indices and the expression levels of HSP70, HSP90, Cyp1a, and MT in the liver were assayed. Results indicated Cd exposure in group H could significantly damage the gill and liver. The SOD activity of gill and liver exhibited an increasing trend with Cd concentrations increasing, and SOD activities increased significantly in group M compared to that of group C. Still, SOD activity significantly decreased in group H. MDA content increased significantly in both the gill and liver, while T-AOC activities were not significantly different in both the gill and liver. By comparison with group C, the activities of ALT and AST in serum were significantly increased in group M and group H; the contents of ALB and TP significantly decreased in group M and group H except for the content slightly increased in the group L; the contents of GLU, TG, and TC did not show significant changes in the group L and the group M, but increased significantly in the group H. The expression levels of HSP70 and HSP90 in the liver exhibited the highest level in group M, whereas the expression levels of MT and Cyp1a were highest in groups H and L, respectively. Our results are intended to provide a reference basis for the safety risk evaluation of Cd and healthy fish farming.

Roles of Cyt-c/Caspase-9/Caspase-3/Bax/Bcl-2 pathway in Cd-induced testicular injury in rats and the protective effect of quercetin

Cadmium (Cd) exposure causes oxidative damage to mitochondria, which would adversely affect rat testicular tissue. Quercetin (Que) is a natural antioxidant with anti-inflammatory, antioxidant and anti-apoptotic effects. However, the mechanism by which Que inhibits Cd-induced apoptosis of testicular cells remains unclear. The purpose of this study was to investigate the role of mitochondrial apoptosis pathway (Cyt-c/Caspase-9/Caspase-3/Bax/Bcl-2 pathway) in inhibiting Cd-induced apoptosis of testicular cells by Que. We used SD rats to simulate Cd chloride exposure by treating all sides of the rats with CdCl2 and/or Que. The levels of GSH and MDA in rat testis were detected using reagent kits. The effects of CdCl2 and/or Que on tissue damage, apoptosis, and gene and protein expression of the Cyt-c/Caspase-9/Caspase-3/Bax/Bcl-2 pathway in rat testis were examined by HE, TUNEL, RNA extraction and reverse-transcriptase polymerase chain reaction (RT-PCR), and Western blot (Wb). The results show that Cd significantly increased the contents of GSH and MDA in rat testis (P < 0.01); conversely, Que significantly reduced the contents of GSH and MDA (P < 0.01). Cd inflicted damage to testicular tissue, and Que addition significantly reduced the damage. Cd increased the number of apoptosis of testicle cells, and Que inhibited testicle-cell apoptosis. In addition, the results of reverse transcription PCR and Wb assays confirmed that, as expected, Cd increased the expression levels of Cyt-c, Caspase-9, Caspase-3, and Bax mRNAs as well as proteins. And at the same time decreased the expression of the anti-apoptotic factor Bcl-2 in the cells. Surprisingly, these effects were reversed when Que was added. Therefore, Que can play an antioxidant and anti-apoptotic role in reducing the testicular tissue damage caused by Cd exposure. This provides a conceptual basis for the later development and utilization of Que as well as the prevention and treatment of tissue damage caused by Cd exposure.

Effects of cadmium exposure during pregnancy on genome-wide DNA methylation and the CREB/CREM pathway in the testes of male offspring rats

This experimental study explored the multigenerational and transgenerational effects of cadmium (Cd) exposure during pregnancy on the testicular tissue and spermatogenesis of male offspring rats. CdCl2 at different doses (0, 0.5, 1, 2 mg/kg/day) were dispensed to pregnant SD rats, thus producing generation F1. Adult females in F1 (PND 56) were mated with untreated fertile males so as to produce generation F2. Likewise, adult females in F2 were mated to produce generation F3. Damages to testicular tissue were observed in all the three generations, with serum testosterone (T) increased in F2 and F3. Notably, the genome-wide DNA methylation level in the testicular tissue of F1 was altered, as was the expression of F1–F3 methyltransferases. In addition, the expression of Creb/Crem pathway, a pathway critical for the metamorphosis from postmeiotic round spermatocytes to spermatozoa, was also remarkably altered in the three generations. In concludion, prenatal Cd exposure might bring multigenerational and transgenerational toxic effects to testes via genome-wide DNA methylation and the regulation of CREB/CREM pathway.