Publications (7)24.92 Total impact
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Article: Developmental toxicity of cypermethrin in embryo-larval stages of zebrafish.
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ABSTRACT: Cypermethrin, a type II pyrethroid insecticide, is widely used throughout the world in agriculture, forestry, horticulture and homes. Though the neurotoxicity of cypermethrin has been thoroughly studied in adult rodents, little is so far available regarding the developmental toxicity of cypermethrin to fish in early life stages. To explore the potential developmental toxicity of cypermethrin, 4-h post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of cypermethrin (0, 25, 50, 100, 200 and 400 μg L⁻¹) until 96 h. Among a suite of morphological abnormalities, the unique phenotype curvature was observed at concentrations as low as 25 μg L⁻¹. Studies revealed that 400 μg L⁻¹ cypermethrin significantly increased malondialdehyde production. In addition, activity of antioxidative enzymes including superoxide dismutase and catalase were significantly induced in zebrafish larvae in a concentration-dependent manner. To further investigate the toxic effects of cypermethrin on fish, acridine orange (AO) staining was performed at 400 μg L⁻¹ cypermethrin and the result showed notable signs of apoptosis mainly in the nervous system. Cypermethrin also down-regulated ogg1 and increased p53 gene expression as well as the caspase-3 activity. Our results demonstrate that cypermethrin was able to induce oxidative stress and produce apoptosis through the involvement of caspases in zebrafish embryos. In this study, we investigated the developmental toxicity of cypermethrin using zebrafish embryos, which could be helpful in fully understanding the potential mechanisms of cypermethrin exposure during embryogenesis and also suggested that zebrafish could serve as an ideal model for studying developmental toxicity of environmental contaminants.Chemosphere 08/2011; 85(6):1010-6. · 3.21 Impact Factor -
Article: Assessment of an association between an aryl hydrocarbon receptor gene (AHR) polymorphism and risk of male infertility.
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ABSTRACT: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of a variety of environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs) and dioxins. We hypothesized that polymorphisms of AHR may result in significant differences in sensitivity to toxic effects of PAHs or dioxins and contribute to susceptibility to male infertility. To address this possibility, we conducted a study including 580 idiopathic infertile subjects and 580 fertile controls to assess associations between the male infertility risk and six tagging single nucleotide polymorphisms of AHR gene. Additionally, correlations between AHR polymorphisms and sperm concentration, levels of DNA fragmentation, and benzo(a)pyrene diolepoxide (BPDE)-DNA adducts in sperm were determined in 420 patients. Genotypes were determined using the ABI OpenArray platform. Sperm DNA fragmentation was evaluated by terminal deoxyribonucleotidyl transferase (TdT)-mediated dUDP nick-end labelling (TUNEL) assay, and sperm BPDE-DNA adducts were measured by immunofluorescent assay using flow cytometry. We found that the G variant of rs2158041 was associated with significantly increased risk of male infertility (adjusted odds ratio 1.53, 95% confidence interval 1.21-1.93; p = 6.0 x 10⁻⁶; GA/AA vs. GG genotypes). Furthermore, patients with rs2158041 AA genotype showed a reduced sperm concentration. In addition, a gradual increase of sperm DNA fragmentation and sperm BPDE-DNA adducts was found among the three rs2158041 subgroups (GG → GA → AA), though the differences were not statistically significant. These results suggested that the AHR polymorphism might be associated with individual risk of male infertility in the Chinese population study.Toxicological Sciences 05/2011; 122(2):415-21. · 4.65 Impact Factor -
Article: Polymorphisms of nucleotide-excision repair genes may contribute to sperm DNA fragmentation and male infertility.
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ABSTRACT: The nucleotide-excision repair (NER) system is crucial for the removal of bulky DNA adducts during spermatogenesis. Dysfunction of its repair capacity is likely related to the increased susceptibility to DNA damage. In this study, four polymorphisms in NER pathway (XPA(-4) G/A, ERCC1 C8092A, XPD Lys751Gln and XPF Ser835Ser) were selected to evaluate their potential impact on sperm DNA damage and male infertility. Genotypes were determined by PCR-restriction fragment length polymorphism. Sperm DNA damage was evaluated by TdT-mediated dUDP nick-end labelling assay. A case-only study of 620 infertile men found a significant association between XPA(-4) G/A polymorphism and sperm DNA damage. Individuals with the XPA(-4) A allele showed more sperm DNA damage and lower sperm concentration than G allele carriers. Further analysis, including 620 patients and 385 controls, revealed a 1.52-fold risk (95% CI 1.08-2.02) of developing male infertility in the XPA(-4) AA carriers compared with noncarriers. Luciferase assay verified that the promoter with the XPA(-4) A allele had a lower transcriptional activity than that with the G allele. These data provide the first evidence that -4 G/A polymorphism in XPA promoter alters its transcriptional activity and, thus, might contribute to sperm DNA damage and male infertility. Sperm DNA integrity is essential for the accurate transmission of genetic information. To our knowledge, few studies have elucidated the effect of DNA repair gene single-nucleotide polymorphisms on sperm DNA integrity, although the DNA repair system is indispensable in maintaining genetic stability and normal spermatogenesis. In this original study, we evaluated the potential impact of the polymorphisms in the nucleotide-excision repair pathway on the risk of sperm DNA damage based on 620 infertile patients and 385 controls, and provided the first evidence that -4 G/A polymorphism in the promoter for the xeroderma pigmentosum group A gene altered its transcriptional activity, which might contribute to sperm DNA damage and male infertility.Reproductive biomedicine online 11/2010; 21(5):602-9. · 2.04 Impact Factor -
Article: Genetic variants in Piwi-interacting RNA pathway genes confer susceptibility to spermatogenic failure in a Chinese population.
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ABSTRACT: The Piwi subfamily of genes is involved in spermatogenesis for the maintenance and meiosis of germline stem cells. Mice bearing targeted mutations in Piwi genes (Miwi, Mili and Miwi2) are sterile with distinct defects in spermatogenesis. We hypothesized that Piwi gene polymorphisms could be a risk factor for spermatogenic failure. For this study, 490 patients with idiopathic azoospermia or oligozoospermia and 468 fertile controls were recruited from an infertility clinic. Nine single nucleotide polymorphisms (SNPs) of four Piwi genes (PIWIL1/HIWI, PIWIL2/HILI, PIWIL3/HIWI3 and PIWIL4/HIWI2) were genotyped using the SNPstream® 12-plex platform and the Taqman method. An SNP in the 3'untranslated region of HIWI2 and a non-synonymous SNP in HIWI3 were significantly associated with an altered risk of oligozoospermia. The variant-containing genotypes of HIWI2 rs508485 exhibited a significantly increased risk, with an odds ratios (OR) of 1.49 [95% confidence interval (CI), 1.02-2.18], and individuals with HIWI3 non-synonymous rs11703684 variant genotypes exhibited a significantly reduced oligozoospermia risk (OR = 0.70; 95% CI, 0.49-1.00). The haplotype analysis showed that a common haplotype of HIWI2 was associated with a significant reduction in the risk of oligozoospermia (OR = 0.73, 95% CI, 0.56-0.97). In addition, to assess the cumulative effects, we performed a combined unfavourable genotype analysis. A significant trend towards increased risk of oligozoospermia with an increasing number of unfavourable genotypes was observed (P for trend < 0.001). We present the first epidemiologic evidence supporting the involvement of genetic polymorphisms in Piwi genes in spermatogenic failure.Human Reproduction 10/2010; 25(12):2955-61. · 4.47 Impact Factor -
Article: Exposure to fenvalerate causes brain impairment during zebrafish development.
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ABSTRACT: Compared with increasing evidence suggesting that fenvalerate is neurotoxic to adults, further information regarding developmental toxicity of this compound attracts more attention. In this study, we used zebrafish as an environmental monitoring model to further explore the potential toxicity of fenvalerate. Our results demonstrated that larvae exposed to fenvalerate for 24-96 h displayed obvious morphological abnormalities, and the LC50 concentrations were 131.95 microg/L (LC50-24h), 107.18 microg/L (LC50-48 h), 21.76 microg/L (LC50-72 h), and 6.25 microg/L (LC50-96 h). To further investigate the effects of fenvalerate on embryos and larvae, acridine orange staining was performed at a 50 microg/L concentration. Staining showed notable signs of apoptosis mainly in the brain. Further studies revealed that fenvalerate induced alterations in SOD activity in larvae were concentration dependent and also related to the length of exposure. Fenvalerate also down-regulated the expression of ogg1 and dlx2 genes in a concentration dependent manner, which indicated that the oxidative-DNA repair system as well as neurogenesis were impaired. In this study, we investigated the toxicity of fenvalerate using zebrafish, that provided new evidence of observable brain impairment during embryogenesis due to fenvalerate exposure and discussed their implications for the development of fenvalerate induced neurotoxicity.Toxicology Letters 09/2010; 197(3):188-92. · 3.23 Impact Factor -
Article: Interactions between exposure to environmental polycyclic aromatic hydrocarbons and DNA repair gene polymorphisms on bulky DNA adducts in human sperm.
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ABSTRACT: Nucleotide excision repair (NER) and base excision repair (BER) are the primary mechanisms for repair of bulky adducts caused by chemical agents, such as PAHs. It is expected that polymorphisms in NER or BER genes may modulate individual susceptibility to PAHs exposure. Here, we evaluate the effects of PAHs exposure and polymorphisms in NER and BER pathway, alone or combined, on polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adducts in human sperm. Sperm PAH-DNA adducts were measured by immunofluorescent assay using flow cytometry in a sample of 465 infertile adults. Polymorphisms of XPA, XPD, ERCC1, XPF, and XRCC1 were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. The PAHs exposure was detected as urinary 1-hydroxypyrene (1-OHP) levels. In multivariate models adjusted for potential confounders, we observed that XRCC1 5'pUTR -T/C, Arg194Trp, Arg399Gln polymorphisms were associated with increased sperm adduct levels. Furthermore, the stratified analysis indicated that adverse effects of XRCC1 Arg194Trp, Arg399Gln polymorphisms on PAH-DNA adducts were detected only in the high PAHs exposure group. These findings provided the first evidence that polymorphisms of XRCC1 may modify sperm PAH-DNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from PAHs exposure.PLoS ONE 01/2010; 5(10). · 4.09 Impact Factor -
Article: Effects of non-occupational environmental exposure to pyrethroids on semen quality and sperm DNA integrity in Chinese men
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ABSTRACT: Observations in several western and Asiatic countries point toward a decline in semen quality which may be associated with environmental exposures. To investigate the effect of environmental exposure to pyrethroids on sperm DNA integrity and semen quality, 240 men were recruited from an infertility clinic through the clinic following strict eligibility screening. Urinary 3-phenoxybenzoic acid (3-PBA) concentration, semen quality, and sperm DNA integrity were evaluated. After adjustment for potential confounders, a significant inverse correlation was observed between the urinary 3-PBA level and the sperm concentration (β = −0.27, 95%CI: −0.41 to −0.12, P < 0.001). Moreover, we also found a significant positive correlation between urinary 3-PBA level and sperm DNA fragmentation (β = 0.27, 95%CI: 0.15–0.39, P < 0.001). Our results suggest that non-occupational environmental pyrethroids exposure may have a negative impact on sperm DNA integrity and semen quality in Chinese males.Reproductive Toxicology 31(2):171-176. · 3.23 Impact Factor
Top co-authors
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Institutions
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2010–2011
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Nanjing Medical University
- • Institute of Toxicology
- • Key Laboratory of Reproductive Medicine
Nanjing, Jiangsu Sheng, China
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