RESUMO
Organic light-emitting materials (OLEMs) are emerging contaminants in the environment and have been detected in various environment samples. However, limited information is available regarding their contamination within the human body. Here, we developed a novel QuEChERS (quick, easy, cheap, effective, rugged, and safe) method coupled with triple quadrupole/high-resolution mass spectrometry to determine OLEMs in breast milk samples, employing both target and suspect screening strategies. Our analysis uncovered the presence of seven out of the 39 targeted OLEMs in breast milk samples, comprising five liquid crystal monomers and two OLEMs commonly used in organic light-emitting diode displays. The cumulative concentrations of the seven OLEMs in each breast milk sample ranged from ND to 1.67 × 103 ng/g lipid weight, with a mean and median concentration of 78.76 and 0.71 ng/g lipid weight, respectively, which were higher compared to that of typical organic pollutants such as polychlorinated biphenyls and polybrominated diphenyl ethers. We calculated the estimated daily intake (EDI) rates of OLEMs for infants aged 0-12 months, and the mean EDI rates during lactation were estimated to range from 30.37 to 54.89 ng/kg bw/day. Employing a suspect screening approach, we additionally identified 66 potential OLEMs, and two of them, cholesteryl hydrogen phthalate and cholesteryl benzoate, were further confirmed using pure reference standards. These two substances belong to cholesteric liquid crystal materials and raise concerns about potential endocrine-disrupting effects, as indicated by in silico predictive models. Overall, our present study established a robust method for the identification of OLEMs in breast milk samples, shedding light on their presence in the human body. These findings indicate human exposure to OLEMs that should be further investigated, including their health risks.
Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Lactente , Feminino , Humanos , Leite Humano/química , Poluentes Ambientais/análise , Bifenilos Policlorados/análise , Espectrometria de Massas , LipídeosRESUMO
OBJECTIVE: To investigate the effect of selenium on cyclophosphamide (CTX)-induced spermatogenic impairment (SI) in mice and its underlying mechanism. METHODS: We equally randomized 36 male KM mice into 3 SI model and 3 control groups, the first 3 treated by intraperitoneal injection of CTX at 100 mg/kg (the SI model control group), CTX plus SI model control group, selenium deficient model group (ï¼Se SI), selenium supplemented model group (+Se SI), while latter 3 by intraperitoneal injection of normal saline (the normal control), selenium deficiency control group (ï¼Se control), selenium addition control group (+Se control), respectively, all once a week for 6 successive weeks. Then we observed the histopathological changes in the testes of all the mice by HE staining, obtained the sperm count in the epididymides, determined the expressions of glutathione peroxidase 4 (GPx4) and SLC7A11 proteins by Western blot and ferroptosis-related genes by RT-qPCR, and examined the changes in the expressions of ferroptosis-related proteins and genes in the GC2-spd cells treated with ferroptosis inhibitors and inducers in combination with different concentrations of inorganic sodium selenite (SeS) and organic selenomethionine (SeM). RESULTS: Compared with the normal controls, the SI model mice showed significantly decreased testicular and prostatic organ coefficients, reduced spermatogenic layers, increased voids, decreased serum ferritin concentration (P<0.05), and elevated transferrin concentration (P<0.05). The organ coefficients were significantly higher in the +Se SI and +Se control than in the ï¼Se SI and ï¼Se control groups (P<0.05, P<0.01), with evident pathological improvement of the testis tissue in the +Se controls. The expressions of the GPx4 and solute carrier family 7 members 11ï¼SLC7A11ï¼ genes in the testis were dramatically down-regulated in the SI model controls (P<0.01), but up-regulated in the +Se SI and +Se control compared with those in the ï¼Se SI and ï¼Se control group (P<0.01 and P<0.05), but there were no statistically significant differences between their protein expressions. The results of in vitro GC2 spd cell experiments indicated that the GPx4 gene and GPx4 protein levels in the - Se group were significantly lower than those in the normal control group (P<0.05), while the SLC7A11 gene level decreased (P<0.01). Different doses of SeS and SeM significantly increased the GPx4 protein expression compared to the average Se group. Low doses of SeM promoted a significant increase in GPx4 gene levels, while high doses of SeS increased the expression levels of SLC7A11 gene and SLC7A11 protein (P<0.05, P<0.01). The Se group showed a significant decrease in the levels of acsl4 and ptgs2 genes compared to the normal control group. SeM promoted the expression of acsl4, while SeS promoted the expression of ptgs2 and fth1 (P<0.01, P<0.05). The intervention results of GC2 spd showed that the Erastin group had a decrease in ptgs2 compared to the normal control group, while the SeS+Erastin and SeM+Erastin groups had an increase in ptgs2 gene expression compared to the Erastin group. However, the ptgs2 expression of Fer-1 was lower than that of the normal control group, and the ptgs2 gene level of SeS+Fer-1 and SeM+Fer-1 groups was lower than that of Fer-1 group (P<0.05); The gene quantity of GPx4 in the SeM+Erastin and SeM+Fer-1 groups increased compared to the Erastin and Fer-1 groups (P<0.01, P<0.05); SeM+Erastin and SeS+Erastin showed a decrease in SLC7A11 compared to the Erastin group, as well as SeM+Fer-1 and SeS+Fer-1 groups compared to the Fer-1 group, accompanied by an increase in acsl4 and fth1 (P<0.01). CONCLUSION: Selenium deficiency causes the reduction of the SLC7A11 and GPx4 gene levels, disorder of ferroptosis-related genes and down-regulation of the GPx4 protein expression in the mouse testis and spermatocytes. Selenium can promote the expression of GPx4, up-regulate the level of SLC7A11, and improve spermatogenesis in the testis of the mouse with SI. There are differences between organic SeM and inorganic SeS in regulating the ferroptosis pathway-related genes.
Assuntos
Ciclofosfamida , Selênio , Espermatogênese , Testículo , Animais , Masculino , Ciclofosfamida/efeitos adversos , Camundongos , Selênio/farmacologia , Espermatogênese/efeitos dos fármacos , Testículo/metabolismo , Testículo/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Ferroptose/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Contagem de Espermatozoides , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Selenito de Sódio/farmacologiaRESUMO
Emerging evidence suggests that selenium plays an essential role in sperm maturation. However, the specific signaling pathway by which selenium exerts effect has not been elucidated. To evaluate the effect of selenium on GPX4-mediated lipid peroxidation and apoptosis in germ cells, selenium deficiency was modeled by culturing GC2-spd cells in serum-free medium. Treatment with 0.5-µM sodium selenite (NaSe) or 5.0-µM selenomethionine (SeMet) significantly improved the proliferation rate and GPX4 protein expression after selenium deficiency. Moreover, NaSe and SeMet decreased the MDA content and lipid peroxidation. When adenovirus was used to knockdown the expression of the GPX4 gene (shRNA-GPX4), the early apoptosis rate of the shRNA-GPX4 cells was significantly higher than that of the EGFP cells. Increased expression of Caspase3 and Bax, as well as MDA content were observed in the shRNA-GPX4 cells compared with EGFP cells. In further, overexpression of the GPX4 gene (ORF-GPX4) cells exhibited increased cell proliferation and decreased MDA content. However, there was no significant difference in 12/15-lox expression both in ORF-GPX4 cells and shRNA-GPX4 cells. Conclusively, GPX4 was involved in the regulation of lipid peroxidation and apoptosis in GC2-spd cells. Selenium played a role in promoting cell proliferation by mediating GPX4. The regulation of GPX4 may occur independently of 12/15-Lox. These findings confirmed the effect of selenium on spermatogenesis and offered a potential target for treating abnormal semen quality in men.
Assuntos
Selênio , Antioxidantes/metabolismo , Apoptose , Células Germinativas/metabolismo , Humanos , Peroxidação de Lipídeos , Masculino , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , RNA Interferente Pequeno/metabolismo , Selênio/metabolismo , Selênio/farmacologia , Selenometionina , Análise do SêmenRESUMO
Assessment of children's exposure risks of phthalates before puberty is important, as phthalates are ubiquitous and are associated with reproductive development. However, relevant data in Pearl River Delta, China are scarce. Nineteen phthalate metabolites were analyzed in urine samples from 1490 primary school starters (6-8 years old) recruited in 2016-2017 using ultra-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS). Nine phthalate metabolites were detected more than 80% of the urine samples. Monobutyl phthalate (MnBP) was the highest metabolite (median, 212⯵g/g creatinine), followed by two short chained phthalate metabolites, four secondary metabolites of di(2-ethylhexyl) phthalate (DEHP), and the primary metabolites of DEHP. The MnBP level was the third highest of those reported worldwide while other metabolites were in the lower range compared with previous studies. Significantly positive associations were found between urinary metabolite levels and family income as well as parent education levels (pâ¯<â¯0.05). Duration since the latest interior decoration was inversely associated with phthalate metabolites (pâ¯<â¯0.05). Significantly positive associations had also been found between the frequency of eating takeaway food and four DEHP metabolites (pâ¯<â¯0.01). The geometric mean of estimated daily intake (EDI) of di-n-butyl phthalate (DnBP), DEHP, di-iso-butyl phthalate (DiBP), dimethyl phthalate, diethyl phthalate and butylbenzyl phthalate (BBzP) were 6.24, 2.67, 1.06, 0.64, 0.44, and 0.01⯵g/kgâ¯bw/day, respectively. Hazard quotient (HQ) was defined as the ratio of EDI and the tolerable daily intake (TDI). Approximately 38% children had HQ DnBP >1 indicating potential reproductive risks caused by DnBP. To evaluate cumulative exposure risks, hazard index (HI) was calculated as the sum of the HQs of DnBP, DiBP, DEHP, and BBzP. Nearly 48% children had HIâ¯>â¯1 suggesting extremely high cumulative risks in children in Pearl River Delta, China. To our best knowledge, this was the largest study on evaluating phthalate exposure among children in China.
Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Criança , China , Humanos , Rios , Maturidade Sexual , Espectrometria de Massas em TandemRESUMO
The occurrence of fluorotelomer alcohols (FTOHs) was investigated in 94 food-contact materials (FCMs). We detected 6:2 FTOH (<0.60-1110 ng/g), 8:2 FTOH (<0.40-8490 ng/g), and 10:2 FTOH (<0.02-9350 ng/g) in most FCM samples, and four longer-chain C14-20 FTOHs were, for the first time, identified in FCMs with relatively high concentrations (<0.02-8450 ng/g for 12:2 FTOH, <0.02-1640 ng/g for 14:2 FTOH, <0.02-372 ng/g for 16:2 FTOH, and <0.02-130 ng/g for 18:2 FTOH). There were three typical profiles of FTOHs that were dominated by 6:2 FTOH (95.6 ± 8.1% in 9 FCMs), 8:2 FTOH (50.9 ± 20.8% in 22 FCMs), and 10:2 FTOH (44.5 ± 20.9% in 30 FCMs), indicating the congener-specific usage of FTOHs for different commercial purposes. All nine detectable FCMs produced in the United States were dominated by 6:2 FTOH, which was significantly different from those produced in China. The median concentration of total FTOHs in eco-friendly paper tableware was 2990 ng/g, which was lower than in popcorn bags (18â¯200 ng/g) but much higher than other FCMs (<0.55-38.7 ng/g). FTOHs could migrate from paper bowls, with migration efficiencies of 0.004-0.24% into water, 0.004-0.24% into 10% ethanol, 0.009-2.79% into 30% ethanol, 0.06-13.0% into 50% ethanol (v/v) simulants, and 0.04-2.28% into oil. Migration efficiencies decreased with increasing carbon chain lengths of FTOHs.
Assuntos
Contaminação de Alimentos , Embalagem de Alimentos , Papel , Álcoois , Biodegradação Ambiental , Fluorocarbonos/análise , HumanosRESUMO
Estrogenic chemicals can induce intersex in fish species leading to disturbance of spermatogenesis and impairment of reproductive success. To overcome the shortcomings of conventional histopathological observation on intersex (low sensitivity, relatively poor accuracy, long experimental periods, as well as laborious and time-consuming), we generated a pMOSP1-EGFP transgenic medaka fish model. In this transgenic fish, the green fluorescence protein (GFP) reporter gene was derived by the regulatory elements of the OSP1 gene, which is a specific and sensitive molecular biomarker for indicating intersex occurrence in male medaka fish exposed to estrogenic chemicals. The transgenic GFP was faithfully expressed in ovaries and in testes with intersex, perfectly mimicking the expression pattern of endogenous OSP1. In intersex testis, the diameters of primary oocytes which could be distinguished by GFP fluorescence observation were as small as 10 µm, lower than that (more than 20 µm) which is observable by histopathology. Using the novel transgenic medaka fish, intersex was observed after 90-day exposure to 0.75 ng/L 17α-ethinyloestradiol (EE2) (0-90 dph), but only at concentrations of at least 1.38 ng/L EE2 by histopathology. An effectiveness of a short-term in vivo assay for screening estrogenic chemicals that can monitor intersex appearance at early sex developmental stage (about 30 dph) in male medaka fish was also demonstrated by assessing the intersex induction of EE2, 17ß-estradiol and 4-nonylphenol. This newly developed assay provides an enhanced ability for screening and testing estrogenic chemicals with the potential to induce intersex and studying their biological impacts.
Assuntos
Transtornos do Desenvolvimento Sexual/etiologia , Monitoramento Ambiental/métodos , Estrogênios/toxicidade , Oryzias/fisiologia , Animais , Animais Geneticamente Modificados , Biomarcadores/metabolismo , Estradiol/toxicidade , Etinilestradiol/toxicidade , Feminino , Genes Reporter , Proteínas de Fluorescência Verde/metabolismo , Masculino , Fenóis/toxicidade , Reprodução/efeitos dos fármacosRESUMO
BACKGROUND: Triclosan (TCS), as an endocrine disrupter, has been found to affect male fertility. However, the potential molecular mechanism is still unknown. We aimed to investigate whether the toxic effects of TCS on spermatocyte cells was mediated by the regulation of microRNA-20a-5â¯P on PTEN. METHODS: GC-2 and TM4 cells were treated with TCS (0.5-80⯵M) for 24 or 48â¯hours. Effect of TCS on proliferation of GC-2 and TM4 cells was detected using a cell counting kit-8 (CCK8) assay. Expression of miR-17 family and autophagy genes were detected. The interaction between miR-20a-5â¯P and PTEN was determined by a dual-luciferase reporter assay. RESULTS: TCS decreased cell proliferation of GC-2 and TM4 cells. Expression of autophagy-related genes and miR-17 family was altered by TCS. PTEN expression was significantly increased, whereas the expression of miR-20a-5â¯P was significantly decreased in GC-2 and TM4 cells. As predicted in relevant databases, there is a binding site of miR-20a-5â¯P in PTEN. The expression of PTEN was significantly down-regulated by the miR-20a-5â¯P mimic. CONCLUSION: As a downstream target of miR-20a-5â¯P, PTEN functioned in the autophagy process of which TCS inhibited the proliferation of spermatocyte cells. Our results provided new ideas for revealing the molecular mechanism and protective strategy on male infertility.
Assuntos
Autofagia , Proliferação de Células , MicroRNAs , PTEN Fosfo-Hidrolase , Espermatócitos , Triclosan , MicroRNAs/genética , MicroRNAs/metabolismo , Masculino , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular , Triclosan/toxicidade , Humanos , Espermatócitos/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , AnimaisRESUMO
In this study, an innovative, integrated nontarget and suspect screening workflow was developed for identifying organophosphate diesters (di-OPEs) using high-resolution mass spectrometry. The workflow featured the utilization of 0.02% acetic acid as a mobile-phase additive, differentiated screening methods for alkyl and aryl di-OPEs, and a combination of electrospray negative ionization and positive ionization. Using this workflow, 18 di-OPEs were identified in the extracts of 75 food contact plastic (FCP) samples sourced from South China. Among these, six alkyl and one aryl di-OPEs were previously unknown (one unequivocal identification and six probable structures based on diagnostic evidence). (Semi)quantification revealed that bis(2,4-di-tert-butylphenyl) phosphate was the major di-OPE in FCPs, with a median concentration of 1079 ng/g (range: 23.4-158,414 ng/g). The migration efficiencies of di-OPEs from an FCP sample to four kinds of food simulants were between 2.58 and 54.3%. This study offered a useful workflow for the comprehensive profiling of di-OPEs in FCPs.
Assuntos
Retardadores de Chama , Organofosfatos , Organofosfatos/análise , Fluxo de Trabalho , Poeira/análise , Ésteres/análise , Retardadores de Chama/análise , China , Monitoramento AmbientalRESUMO
The presence of mutagenic and carcinogenic nitrosamines in groundwater is of great concern. In this study, eight nitrosamines including N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosomethylethylamine (NMEA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), N-nitrosopiperidine (NPIP), N-nitrosodi-n-propylamine (NDPA), and N-nitrosodi-n-butylamine (NDBA) and corresponding secondary amines were investigated in shallow groundwater, river water, and wastewater samples collected from the Jialu River basin. The total concentrations of nitrosamines and secondary amines in groundwater were ND-101.1 ng/L and 0.36-4.38 µg/L, respectively. NDMA and its secondary amine DMA (44.7%/40.1%) were the predominant compounds in groundwater, followed by NDEA/DEA (21.7%/29.3%) and NDBA/DBA (26.4%/27.4%). Relatively high concentrations of these six compounds were also observed in river water that was influenced by the direct discharge of industrial and domestic wastewater. Using acesulfame as a quantitative population marker, the contribution of domestic sources to the concentrations of nitrosamines and secondary amines was 39-85% in downstream reaches of the Jialu River, and that of industrial sources was estimated to be 65-98% in other sites of the area. Both on-site leakage of domestic and industrial wastewater and leaching from river water would contribute to the occurrence of target pollutants in groundwater. The target pollutants posed a cancer risk of 4.12 × 10(-5) to the local populations due to the direct usage of groundwater as potable water.
Assuntos
Aminas/análise , Carcinógenos Ambientais/análise , Água Subterrânea/análise , Nitrosaminas/análise , Poluentes Químicos da Água/análise , China , Cromatografia Líquida , Monitoramento Ambiental , Rios/química , Esgotos/análise , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
BACKGROUND: The antimicrobial agent triclosan (TCS) has attracted much attention worldwide because of its pervasive existence in the human body and environment. TCS exposure has been reported to be associated with decreased male reproductive function. However, few studies have investigated these associations in humans. OBJECTIVE: To examine the relationship between TCS in urine and male semen quality. METHODS: A total of 406 men from a reproductive clinic were enrolled in this study. Urinary TCS concentrations were determined by ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry. Sixteen semen parameters were assessed according to the guidelines of World Health Organization (WHO), including parameters for volume, count, motility, and motion. We used multivariate linear regression models and restricted cubic splines to estimate the linear and non-linear associations between TCS exposure and semen parameters, respectively. Logistical regression models were further applied to explore the associations with abnormal semen quality. RESULTS: TCS was detected in 74.6% of urine specimens. The monotonous trend of TCS tertiles and continuous TCS levels with all semen quality parameters were not observed in multivariate linear regression models (p > 0.05). However, compared with those in the lowest tertile, subjects in the second tertile showed significantly higher linearity and wobble (p < 0.05), indicating potential effects on sperm motion. In the models using restricted cubic splines with 3-5 knots, there were no significant non-linear associations between TCS exposure and any semen quality parameter. In addition, TCS tertiles were not associated with the risk of abnormal semen quality (i.e., count and motility) in the logistical regression models. CONCLUSION: Our results revealed that low-level TCS exposure may have limited (none or modest) effects on male semen quality, potentially inducing some fluctuations. Further mechanistic studies on low levels of exposure are needed.
Assuntos
Triclosan , China , Estudos Transversais , Humanos , Masculino , Sêmen , Análise do Sêmen , Contagem de Espermatozoides , Espermatozoides , Triclosan/urinaRESUMO
AIMS: Low sperm quality, a crucial factor of male infertility, is becoming a public health issue all over the world. In male reproductive system, autophagy plays an important role in maintaining physiological functions. There exist conjectures that disordered autophagy autophagy might be related to low sperm quality. However, there is no evidence can confirm that. This study aims to investigate the association between autophagy-associated genes and low sperm quality. METHODS: Sperm samples of low sperm quality cases and matched controls were included to select differential expressed genes (DE genes) by autophagy-related functional gene microarray analysis. Then, 104 cases and 250 controls were included to validate the expression of four important autophagy genes (CXCR4, ESR1, PTEN and LC3B). Based on the obtained DE gene, gene Ontology and pathway analyses were conducted. RESULTS: Chip results showed that expression of all 18 DE genes were decreased in the cases compared to the controls (P < 0.05). Expression of ESR1 were verified to be significantly decreased (P < 0.05). CONCLUSION: Our results provided clues with the association among down-regulated expression of autophagy regulating and associated genes and low sperm quality. These findings revealed possible role of impaired autophagy in the mechanism of low sperm quality. Moreover, these may also provide potential targets for the treatment of low sperm quality.
Assuntos
Autofagia/genética , Espermatozoides/metabolismo , Adulto , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Humanos , Masculino , Análise do SêmenRESUMO
BACKGROUND: Several in vitro and in vivo studies have demonstrated the effects of phthalates on androgen synthesis, and the adverse outcomes of phthalate exposure on male reproductive function have been reported. However, the direct relationship among these three factors remains unknown. OBJECTIVE: To explore the potential roles of steroids involved in androgen synthesis in the association between phthalate exposure and semen quality. METHODS: Eighteen phthalate metabolites (mPAEs) and nine steroids were analyzed in semen samples of 403 male participants aged 18-54 years from a hospital in Shenzhen, China. The associations across phthalate metabolites, steroids, and eleven semen quality parameters were evaluated by multivariate linear regression and logistical regression models. The potential contributions of steroids to the associations between phthalate metabolites and semen quality outcomes were explored by mediation effect analysis. RESULTS: In this cross-sectional study, mono-n-butyl phthalate (MnBP) was inversely associated with nine continuous semen quality parameters in a dose-dependent manner (all p for trend < 0.05). Positive associations were observed between MnBP tertiles and androstenedione (ADD) and pregnenolone (PGL), of which only ADD was significantly associated with sperm quality (i.e., motility, p < 0.05). The estimated average mediated effects of seminal ADD on the associations between MnBP and lower sperm motility parameters (i.e., total motility, TR; progressive motility, PR; curvi-linear velocity, VCL) were 6.4-11.9% (all p < 0.05). The potential mediated effects of ADD on the increasing risks of TR (9.8%) and PR (8.5%) abnormalities induced by MnBP exposure were also observed in logistical regression analysis. CONCLUSION: Our results indicated that androgen synthesis in reproductive system may be potentially affected by phthalate exposure, thereby resulting in reduced sperm motility in adult men. Further studies are needed to understand the actual roles and underlying mechanism of action of androstenedione on these associations.
Assuntos
Androgênios , Ácidos Ftálicos , Adolescente , Adulto , China , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Ftálicos/toxicidade , Sêmen , Análise do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Adulto JovemRESUMO
The non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and diclofenac are highly prescribed worldwide and their presence in aquatic system may pose a potential risk to aquatic organisms. Here, we systematically assessed their cardiovascular disruptive effects in zebrafish (Danio rerio) at environmentally relevant concentrations between 0.04 and 25.0⯵g/L. Ibuprofen significantly increased the cardiac outputs of zebrafish embryos at actual concentrations of 0.91, 4.3 and 21.9⯵g/L. It up-regulated the blood cell velocity, total blood flow and down-regulated the blood cell density at concentrations of 4.3⯵g/L and higher. In comparison, diclofenac led to inhibition of spontaneous muscle contractions and decreased hatching rate of zebrafish embryos at the highest concentration (24.1⯵g/L), while it had negligible effects on the cardiac physiology and hemodynamics. Transcriptional analysis of biomarker genes involved in cardiovascular physiology, such as the significantly up-regulated nppa and nkx2.5 expressions response to ibuprofen but not to diclofenac, is consistent with these observations. In addition, both ibuprofen and diclofenac altered the morphology of intersegmental vessels at high concentrations. Our results revealed unexpected cardiovascular functional alterations of NSAIDs to fish at environmental or slightly higher than surface water concentrations and thus provided novel insights into the understanding of their potential environmental risks.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/toxicidade , Diclofenaco/administração & dosagem , Diclofenaco/toxicidade , Ibuprofeno/administração & dosagem , Ibuprofeno/toxicidade , Organogênese/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Peixe-Zebra/embriologia , Peixe-Zebra/crescimento & desenvolvimento , Animais , Embrião não Mamífero/efeitos dos fármacosRESUMO
As a crucial factor in male reproduction, androgens may represent an intermediate biological mechanism linking metal exposure with effects on semen quality. This study aimed to investigate the association between metal exposure and semen quality, and to assess the mediating role of seminal androgens between metal exposure and semen quality. We investigated the presence of 10 metals in semen and assessed their effect on semen quality in 1136 men recruited from a hospital in Shenzhen, China. Of these, 464 subjects were randomly selected for 4 androgens detection in semen. Cross-sectional associations between single/multiple metals, androgen levels and semen quality were explored by multivariable linear regressions. Mediation analysis was performed to detect the role of seminal androgens on the association between metal exposure and semen quality. Seminal selenium and iron were positively associated with both sperm concentration and total sperm count. Negative associations were observed between both manganese and zinc and sperm concentration, molybdenum and total sperm count, copper and sperm motility. Furthermore, we found significant dose-dependent relationships between both iron and selenium levels and dihydrotestosterone (DHT), arsenic levels and testosterone, as well as zinc and dehydroepiandrosterone. Mediation analysis indicated that higher seminal iron and selenium were associated with an increasing sperm concentration after controlling for DHT, with 10.32% and 12.89% of these associations were mediated by DHT, respectively. A similar mediation effect of DHT was observed in the associations between iron and selenium levels and total sperm count (13.39% and 21.57% mediation, respectively). Our findings suggested that the presence of selenium and iron in semen was beneficial to sperm concentration and total count. Seminal manganese, zinc, molybdenum and copper may be associated with reduced semen quality. The associations between seminal selenium and iron and sperm concentration and total count were partially explained by the concomitant variation of seminal DHT.
Assuntos
Androgênios , Análise do Sêmen , China , Estudos Transversais , Humanos , Masculino , Metais , Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , EspermatozoidesRESUMO
Atherosclerosis (AS), a severe disease characterized by an accumulation of lipids and fibers in the large arteries, is the most important contributor to ischemic stroke (IS). Although microRNAs (miRNAs) have been found in circulating blood, the role of miRNAs in the progression of AS remains unknown. In a previous study, we demonstrated that the spleen tyrosine kinase (Syk) gene plays a vital role in the process of IS. In the present study, we aimed to clarify whether the miRNAs targeting the Syk gene might slow the development of AS. Candidate miRNAs were screened in U937 and THP-1 cells via Bioinformatics analyses, RT-qPCR and dual-luciferase reporter assay. ApoE-/- mice were used as an AS animal model. RAAV transfection was performed to identify the roles of Syk gene and miRNAs in the development of AS in ApoE-/- mice. HE staining, Oil red O staining and immunohistochemistry were used to determine the mechanism of AS. RT-qPCR and western blotting were performed to determine the expressions of miRNAs and proteins, respectively. Over-expression of the Syk gene accelerated the development of AS. miR-377 effectively mediated the expression of the Syk gene in vitro and in vivo experiments. Further analysis indicated that over-expression of miR-377 partly alleviated the development of AS by down-regulating the expression of the Syk gene. This study identifies a novel role of miR-377 in AS via targeting Syk.
Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/genética , MicroRNAs/metabolismo , Quinase Syk/genética , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Aorta/metabolismo , Aorta/patologia , Aterosclerose/sangue , Aterosclerose/patologia , Sequência de Bases , Linhagem Celular , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Estresse Oxidativo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Quinase Syk/metabolismoRESUMO
BACKGROUND: Phytoestrogens (PEs) are naturally estrogen-like chemicals, and increasing evidences have indicated their endocrine disruption effects on male reproductivity, but the conclusions from previous epidemiological studies were controversial. OBJECTIVE: To examine the associations between nine phytoestrogens in semen and semen quality in a Chinese population. METHODS: In this cross-sectional study, a total of 1319 reproductive-aged men were recruited from Shenzhen, China. Semen phytoestrogens were measured by ultra-performance liquid chromatography and tandem mass spectrometry. Semen quality was assessed by sperm concentration, sperm count, progressive motility, total motility, volume, and the sperm motion parameters. Both multivariate linear regression and logistic regression models were conducted to evaluate the associations between semen phytoestrogens and semen quality with adjustment for confounders. RESULTS: In logistic regression models, we found significant associations between semen secoisolariciresinol (SEC) and lower sperm concentrations (odd ratios (OR): 2.38; 95% confidence interval, 95% CI: 1.47, 3.93), sperm counts (OR: 2.27; 95% CI: 1.34, 3.94), and total motility (OR: 1.55; 95% CI: 1.08, 2.24). Negative associations were also observed for semen genistein (GEN) with sperm counts (OR: 2.28; 95% CI: 1.29, 4.14; p for trendâ¯=â¯0.04) and sperm concentrations (OR: 1.98; 95% CI: 1.21, 3.03; p for trendâ¯=â¯0.07). Semen naringenin (NAR) were found to be positively associated with progressive motility (OR: 0.57; 95% CI: 0.38, 0.83) and total motility (OR: 0.57; 95% CI: 0.40, 0.81). Results from multivariate linear regression models were similar to those from logistic regression models for semen SEC, GEN, and NAR. CONCLUSIONS: We suggested that semen levels of phytoestrogens may be associated with semen quality in men. Further investigations are warranted to confirm the findings in prospective studies and to explore the underlying mechanism.
Assuntos
Fitoestrógenos/farmacologia , Sêmen/efeitos dos fármacos , Adulto , Butileno Glicóis/farmacologia , China , Estudos Transversais , Genisteína/farmacologia , Humanos , Lignanas/farmacologia , Masculino , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacosRESUMO
While the U.S. EPA has issued a draft report with a 1% TCDD effective dose (ED01) of 87.9pg/kg/day based on continuous integration of key scientific evidence, a detailed and comprehensive uncertainty analysis has not been well documented. In this study, a new estimate for ED01 was derived based on uncertainty analysis by quantitatively assessing the potential bias arising from the selection of kinetic models, dose-response models and cohorts. The cumulative serum lipid concentration (CSLC) and cumulative body burden (CBB) were reconstructed as dose metrics using a concentration- and age-dependent pharmacokinetic model (CADM), physiologically based pharmacokinetic model (PBPK), and age-dependent half-life model (FV), and the reconstructed dose metrics based on CADM and PBPK were generally higher than those based on the FV model. Three dose-response curves (linear, multiplicative and power) were used to link dose metrics and cancer risk to estimate ED01, and the linear model resulted in the lowest ED01, followed by the power model and multiplicative model, for the same cohort. Meanwhile, ED01 based on the CADM model was the highest, followed by those based on the PBPK model and first-order model. Finally, the ED01 was estimated to be 17.03±7.83pg/kg/day by statistically analyzing the distribution of ED01 values based on various kinetic models, cohorts and dose-response models. The study presented here strengthens the scientific basis for understanding the potential health implications of TCDD exposure.
Assuntos
Poluentes Ambientais/sangue , Neoplasias , Exposição Ocupacional/efeitos adversos , Dibenzodioxinas Policloradas/sangue , Teratogênicos/toxicidade , Carga Corporal (Radioterapia) , Poluentes Ambientais/farmacocinética , Poluentes Ambientais/toxicidade , Alemanha/epidemiologia , Meia-Vida , Humanos , Modelos Lineares , Masculino , Modelos Teóricos , Neoplasias/induzido quimicamente , Neoplasias/mortalidade , Dibenzodioxinas Policloradas/farmacocinética , Dibenzodioxinas Policloradas/toxicidade , Teratogênicos/farmacocinética , Incerteza , Estados Unidos/epidemiologiaRESUMO
The SOS/umuC assay was performed in conjunction with analytical measurements to identify potential genotoxins in river and adjacent ground waters in the Jialu River basin, China. The major genotoxic activities of the river and adjacent ground waters occurred in the same two fractions (F4 and F11) when assayed using the Salmonella typhimurium strain TA1535/pSK1002. This indicates that ground water near the Jialu River was influenced by the river water. LC-MS/MS analysis indicated that flumequine accounted for 86% and 76% of the genotoxicity in fraction F11 of the river and adjacent ground waters, respectively. When HPLC fractions were tested using the strain NM3009, three fractions showed genotoxic activities for river water sample, while no fractions from ground water samples elicited genotoxic activities. The specific response to the strain NM3009 in one fraction compared with the strain TA1535/pSK1002 suggested the presence of nitroarenes. However, we failed to identify the exact nitroarenes when GC-MS analysis was used to analyze nitroarenes which are well detected in air and soil samples in previous papers.