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1.
J Hazard Mater ; 421: 126683, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34315024

RESUMO

Experimental studies have demonstrated that disinfection byproducts (DBPs) can cause ovarian toxicity including inhibition of antral follicle growth and disruption of steroidogenesis, but there is a paucity of human evidence. We aimed to investigate whether urinary biomarkers of exposure to drinking water DBPs were associated with ovarian reserve. The present study included 956 women attending an infertility clinic in Wuhan, China from December 2018 to January 2020. Antral follicle count (AFC), ovarian volume (OV), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) were measured as indicators of ovarian reserve. Urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were assessed as potential biomarkers of drinking water DBP exposures. Multivariate linear and Poisson regression models were applied to estimate the associations of urinary DCAA and TCAA concentrations with indicators of ovarian reserve. Elevated urinary DCAA and TCAA levels were monotonically associated with reduced total AFC (- 5.98%; 95% CI: - 10.30%, - 1.44% in DCAA and - 12.98%; 95% CI: - 17.00%, - 8.76% in TCAA comparing the extreme tertiles; both P for trends ≤ 0.01), and the former was only observed in right AFC but not in left AFC, whereas the latter was estimated for both right and left AFC. Moreover, elevated urinary TCAA levels were monotonically associated with decreased AMH (- 14.09%; 95% CI: - 24.79%, - 1.86% comparing the extreme tertiles; P for trend = 0.03). These negative associations were still observed for the exposure biomarkers modeled as continuous variables. Our findings suggest that exposure to drinking water DBPs may be associated with decreased ovarian reserve.


Assuntos
Água Potável , Reserva Ovariana , Biomarcadores , Estudos Transversais , Desinfecção , Feminino , Humanos
2.
Chemosphere ; 288(Pt 1): 132464, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34619260

RESUMO

Studies indicate that phthalates can disrupt spermatogenesis and lead to the reduction of semen quality. However, the underlying mechanisms remain unclear. This study aimed to examine the associations of phthalate exposures as individual chemicals and mixtures with spermatogenesis-related miRNA106a. We detected eight phthalate metabolites in repeated urine samples and a single seminal plasma specimen among 111 men from an infertility clinic in Wuhan, China. Spermatogenesis-related miRNA106a was measured in seminal plasma. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) models to separately evaluate the associations of phthalate metabolites as individual chemicals and mixtures with spermatogenesis-related miRNA106a. Elevated tertiles of urinary mono (2-ethylhexyl) phthalate (MEHP) was associated with decreased miRNA106a (-61.71%; 95%CI: 81.92, -18.93% for the highest vs. lowest tertile; P for trend = 0.01). Similarly, an inverse exposure-response relationship between seminal plasma MEHP concentrations and miRNA106a was also observed (-59.44%; 95%CI: 79.19, -20.95% for the highest vs. lowest tertile; P for trend = 0.01). The BKMR models showed that the mixtures of seminal plasma phthalate metabolites were associated with decreased miRNA106a when the chemical mixtures were ≥35th percentile compared to their medians. Nonlinear associations with miRNA106a were estimated for urinary and seminal plasma MEHP while fixing other phthalate metabolites at their medians. Our findings suggest that mixtures of phthalate metabolites in seminal plasma were negatively associated with spermatogenesis-related miRNA106a, and individual MEHP was the major contributor to the adverse effects.


Assuntos
Ácidos Ftálicos , Sêmen , Teorema de Bayes , Exposição Ambiental , Clínicas de Fertilização , Humanos , Masculino , Análise do Sêmen , Espermatogênese
4.
Environ Sci Technol ; 55(23): 16011-16022, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34813313

RESUMO

Disinfection byproduct (DBP) exposure has been associated with birth size, pregnancy oxidative stress, and other adverse perinatal outcomes. However, little is known about the potential effect of prenatal DBP exposure on intrauterine growth. The present study included 1516 pregnant women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort who were measured for four blood trihalomethanes [i.e., chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and two urinary haloacetic acids [i.e., dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)] across pregnancy trimesters. Second- and third-trimester fetal ultrasound measures of the abdominal circumference (AC), head circumference, biparietal diameter, femur length, and estimated fetal weight and birth weight were converted into z-scores. After adjusting for potential confounders, linear mixed models showed a decreasing AC z-score across tertiles of blood brominated THM (Br-THMs, the sum of BDCM, DBCM, and TBM) and total THM (THM4, the sum of Br-THMs and TCM) concentrations (both p for trend <0.01). We also observed a decreasing AC z-score across categories of blood TBM during pregnancy trimesters (p for trend = 0.03). Urinary haloacetic acids were unrelated to fetal growth parameters. In summary, prenatal exposure to THMs, particularly during the first trimester, was associated with reduced fetal abdominal circumference.

5.
Environ Int ; 157: 106838, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34450548

RESUMO

BACKGROUND: Toxicological studies suggest that maternal exposure to disinfection by-products (DBPs) can impair fetal neurodevelopment. However, evidence from epidemiological studies is scarce and the underlying mechanisms remain unclear. OBJECTIVE: To explore the trimester-specific associations between maternal blood trihalomethane (THM) and urinary haloacetic acid (HAA) concentrations and neonatal neurobehavioral development, and the potential mediating role of oxidative stress (OS). METHODS: We included 438 pregnant Chinese women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort. Biospecimens were repeatedly collected across trimesters and measured for blood THMs, urinary HAAs, and urinary OS biomarker concentrations. On the third day after birth, the Neonatal Behavioral Neurological Assessment (NBNA) test was administered to newborns. Associations of trimester-specific DBP measurements and OS biomarkers with neonatal NBNA scores were assessed using linear regression models with generalized estimating equations. The potential mediating role of maternal OS biomarkers was also investigated using mediation analyses. RESULTS: After adjusting for potential confounders, blood bromodichloromethane (BDCM) concentrations in the first trimester were inversely associated with NBNA scores [percent change comparing the extreme BDCM tertiles = -28.1% (95% CI: -55.2%, -0.88%); p for trend = 0.043]. Besides, third-trimester urinary trichloroacetic acid (TCAA) concentrations were inversely associated with NBNA scores [percent change comparing the extreme TCAA tertiles = -32.9% (95% CI: -64.7%, -1.0%); p for trend = 0.046]. These inverse associations differed across pregnancy trimesters (Type 3p-value = 0.066 and 0.053, respectively) and were stronger in male infants and mothers aged ≥25 years. There was no evidence of mediating effect by 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), or 8-iso-prostaglandin F2α (8-isoPGF2α). CONCLUSIONS: Higher prenatal BDCM and TCAA concentrations during specific pregnancy trimesters were associated with lower NBNA scores. However, additional research is required to investigate underlying mechanisms.


Assuntos
Desinfecção , Exposição Materna , Feminino , Humanos , Recém-Nascido , Masculino , Exposição Materna/efeitos adversos , Estresse Oxidativo , Gravidez , Trimestres da Gravidez , Ácido Tricloroacético , Trialometanos/toxicidade
6.
Front Immunol ; 12: 666909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149702

RESUMO

Background: Atezolizumab plus chemotherapy has been recommended as a first-line treatment option for patients with advanced non-small cell lung carcinoma (NSCLC) irrespective of programmed cell death-ligand 1 (PD-L1) expression. Currently, little is known about the efficacy and treatment-related adverse effects (TRAEs) of subtracting chemotherapy from the combination for patients with high PD-L1 expression. Thus, we performed an indirect comparison between atezolizumab plus chemotherapy and atezolizumab alone. Methods: A total of five eligible randomized controlled trials (RCTs) were identified from PubMed, EMBASE, and Cochrane Central controlled trial registries, using keywords including atezolizumab, PD-1, PD-L1, NSCLC, and RCT. The clinical outcomes of objective response rate (ORR), progression-free survival (PFS), OS, and TRAEs were extracted and evaluated. Using indirect analysis, the efficacy and TRAEs were compared between arm A (atezolizumab plus chemotherapy) and arm C (atezolizumab), linked by arm B (chemotherapy). Results: Direct comparison revealed that both atezolizumab plus chemotherapy (HR 0.65, P = 0.003) and atezolizumab alone (HR 0.59, P = 0.010) significantly improved OS compared with chemotherapy. More importantly, the indirect comparison showed that atezolizumab plus chemotherapy was not superior to atezolizumab regarding OS (RR 1.10, P =0.695) and ORR (RR 1.11, P = 0.645). However, patients who received atezolizumab combined with chemotherapy experienced more ≥ grade 3 TRAEs (RR 4.23, P<0.001) and TRAEs leading to drug discontinuation (RR 3.60, P<0.001) than those treated with atezolizumab monotherapy. Conclusions: Atezolizumab monotherapy might be a better treatment option for patients with advanced NSCLC and high PD-L1 expression than atezolizumab plus chemotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Sci Total Environ ; 784: 147184, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-33901963

RESUMO

BACKGROUND: Exposure to bisphenol A (BPA) has been associated with various adverse health outcomes. Recently, an increasing concern on its alternatives such as bisphenol S (BPS) and bisphenol F (BPF) has been aroused due to the restriction use of BPA. Few studies have identified predictors of exposure to BPA alternatives and assessed their health risks. OBJECTIVE: The aim of this study was to identify predictors of BPA and its alternatives and to assess their health risks among pregnant women. METHODS: We detected first morning urinary concentrations of BPA and its alternatives (BPS and BPF) among 1097 pregnant women from an established Chinese cohort. A questionnaire was conducted to obtain demographic characteristics, dietary habits, and lifestyles. We examined the predictors of creatinine-adjusted urinary BPA and its alternatives concentrations using multivariable linear regression. Risk assessment of exposure to BPA and its alternatives was calculated based on the estimated of daily intake (EDI). RESULTS: Geometric means of creatinine-adjusted urinary BPA, BPF, and BPS were 0.92, 0.12, and 0.08 µg/g creatinine, respectively. Pregnant women from Wuhan had lower concentrations of BPA, BPF, and ∑BPs (sum of BPA, BPF, and BPS) than those from Xiaogan. Intake of fried food was related to higher concentrations of BPA, and intake of pickled food was associated with higher concentrations of BPF and ∑BPs. The maximum EDI values for exposure to BPA, BPF, BPS, and ∑BPs ranged from 5.6428 to 13.3356 nmol/kg body weight/day, which were below the tolerable daily intake (TDI) for BPA defined by the European Food Safety Authority (EFSA) (18 nmol/kg body weight/day). The maximum hazard index (HI) value was 0.7409. CONCLUSION: Several predictors identified in this study may inform public recommendations to reduce exposure to BPA and its alternatives.


Assuntos
Compostos Benzidrílicos , Gestantes , Estudos de Coortes , Feminino , Humanos , Fenóis , Gravidez , Medição de Risco
8.
Environ Int ; 146: 106305, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395947

RESUMO

BACKGROUND: Bisphenol A (BPA) can cause detrimental effects on fetal growth. However, the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on fetal growth are less known. OBJECTIVE: To investigate the relationships of prenatal BPA, BPF, and BPS exposures with fetal growth parameters and gestational age. METHODS: Urinary BPA, BPF, and BPS were measured in 1,197 pregnant women before delivery in a Chinese cohort. The associations of prenatal exposure to BPA, BPF, and BPS with fetal growth parameters and gestational age were examined, and associations stratified by fetal sex were also conducted. We used a restricted cubic splines (RCS) model to examine the dose-response associations between exposures and outcomes. RESULTS: Maternal urinary BPA and BPF were negatively related to birth length (-0.30 cm, 95% CI: -0.44, -0.15 and -0.21 cm, 95% CI: -0.36, -0.07 comparing the extreme exposure groups, respectively, both p for trends < 0.01). These associations were more pronounced in girls with inverted U-shaped dose-response relationships. Maternal urinary BPA and BPF were positively related to ponderal index (0.05 g/cm3 × 100, 95% CI: 0.01, 0.09 and 0.04 g/cm3 × 100, 95% CI: 0.01, 0.08 comparing the extreme exposure groups, respectively, both p for trends = 0.02), and maternal urinary BPS was associated with shorter gestational age (-0.20 weeks, 95% CI: -0.37, -0.03 comparing the extreme exposure groups, p for trend = 0.02). These associations were only observed in girls and exhibited a linear dose-response relationship. CONCLUSIONS: Prenatal BPA, BPF, and BPS exposures were associated with detrimental effects on fetal growth parameters, and stronger effects were noted in female infants.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Compostos Benzidrílicos/toxicidade , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Fenóis , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
9.
Ecotoxicol Environ Saf ; 208: 111694, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396025

RESUMO

Experimental studies have shown that nonradioactive strontium (Sr), in the form of Sr2+, have a positive effect on semen quality, but human evidence is lacking. This study aimed to examine the associations between nonradioactive Sr exposure and semen quality in Chinese men (n = 394). We recruited men who presented at an infertility clinic in Wuhan, China to seek for semen parameter analyses. Urinary Sr concentration as an exposure biomarker was measured using inductively coupled plasma mass spectrometer. We estimated the associations between urinary Sr concentrations and semen parameters using multivariable logistic and linear regression models. In multivariable linear regressions models, positive dose-response associations were estimated for sperm concentration, motility, and count across increasing urinary Sr quartiles (all p for trends<0.05), and the consistent positive associations were also observed for urinary Sr concentration modeled as a continuous exposure. In multivariable logistic models, decreased risks of below-reference sperm concentration, motility, and count were also estimated across increasing urinary Sr quartiles (all p for trends<0.05). Our results suggest that nonradioactive Sr exposure may have a beneficial effect on semen quality, but more investigations are warranted to confirm the results.


Assuntos
Exposição Ambiental/análise , Análise do Sêmen , Estrôncio/urina , Adulto , Biomarcadores/urina , China , Clínicas de Fertilização , Humanos , Masculino , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides/citologia
10.
Chemosphere ; 268: 128856, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33189401

RESUMO

Toxicological and epidemiologic evidence has suggested that exposure to disinfection by-products (DBPs) impairs semen quality, while the underlying biological mechanisms remain unclear. This study aimed to examine the mediating role of oxidative stress in association between DBP exposure and semen quality. We measured a urinary biomarker of DBP exposure [trichloroacetic acid (TCAA)] and three urinary biomarkers of oxidative stress [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] among men from an infertility clinic (n = 299). The associations of oxidative stress biomarkers with urinary TCAA and semen quality were evaluated using multivariable linear regression models, and the mediating role of oxidative stress biomarkers was assessed by a mediation analysis. Urinary TCAA was positively associated with urinary 8-OHdG and 8-isoPGF2α in a dose-response manner (both P for trend < 0.001). Significantly inverse dose-response associations were observed between urinary 8-isoPGF2α and sperm concentration and between urinary 8-OHdG and sperm motility (both P for trend < 0.05). The mediation analysis indicated a significant indirect effect of urinary 8-isoPGF2α in the association between urinary TCAA and decreased sperm concentration (P = 0.01). Our results suggest that lipid peroxidation may be an intermediate mechanism by which DBP exposure impairs semen quality.


Assuntos
Clínicas de Fertilização , Análise do Sêmen , Biomarcadores , Desinfecção , Exposição Ambiental/análise , Humanos , Masculino , Análise de Mediação , Estresse Oxidativo , Motilidade Espermática
11.
Environ Health Perspect ; 128(10): 107001, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33026246

RESUMO

BACKGROUND: Some disinfection by-products (DBPs) are reproductive and developmental toxicants in laboratory animals. However, studies of trimester-specific DBP exposure on adverse birth outcomes in humans are inconsistent. OBJECTIVE: We examined whether trimester-specific blood and urinary biomarkers of DBP were associated with small for gestational age (SGA), low birth weight (LBW), and preterm birth. METHODS: A total of 4,086 blood and 3,951 urine samples were collected across pregnancy trimesters among 1,660 mothers from Xiaogan City, China. Blood samples were quantified for biomarkers of trihalomethanes (THMs): chloroform (TCM), bromodichloromethane, dibromochloromethane, and bromoform. Urine samples were quantified for biomarkers of haloacetic acids (HAA): dichloroacetic acid and trichloroacetic acid. Birth outcomes were abstracted at delivery from medical records. We used Poisson regression models with log link functions to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for SGA, LBW, and preterm birth across tertiles (or categories) of DBP biomarker concentrations measured across pregnancy trimesters. We also examined the relative exposure differences across gestation comparing adverse outcomes with normal births using mixed-effects models. RESULTS: Blood TCM concentrations in the second trimester were associated with an elevated risk of SGA comparing middle vs. lowest (RR, 2.34; 95% CI: 1.02, 5.35) and highest vs. lowest (RR, 2.47; 95% CI: 1.09, 5.58) exposure groups. Third-trimester blood TCM concentrations were also associated with an increased risk of SGA comparing the second tertile with the first (RR, 2.61; 95% CI: 1.15, 5.92). We found that maternal blood TCM concentrations were significantly higher for SGA compared with non-SGA births across the period from 23 to 34 wk gestation. Other blood and urinary DBP biomarkers examined were unrelated to SGA, LBW, or preterm birth. CONCLUSION: Blood TCM concentrations in mid to late pregnancy were associated with an increased risk of SGA, whereas other biomarkers of DBPs examined across pregnancy were not associated with birth outcomes. https://doi.org/10.1289/EHP7195.


Assuntos
Desinfetantes/metabolismo , Hidrocarbonetos Clorados/urina , Exposição Materna/estatística & dados numéricos , Complicações do Trabalho de Parto/epidemiologia , Trialometanos/sangue , Poluentes Químicos da Água/metabolismo , Adulto , Peso ao Nascer , China/epidemiologia , Desinfecção , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Razão de Chances , Gravidez , Terceiro Trimestre da Gravidez , Trimestres da Gravidez , Nascimento Prematuro
12.
Dose Response ; 18(2): 1559325820917829, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32704240

RESUMO

Colon cancer (CC) is considered one of the most common and lethal malignancies occurring both in male and female. Its widespread prevalence demonstrates the need for novel diagnostic and prognostic biomarkers for CC. Emerging evidence has shown that small nucleolar RNAs play critical roles in tumor development. In this study, we investigated the expression profile and functions of SNORD16 in CC. Our data showed that SNORD16, rather than its host gene (RPL4), was upregulated in CC cell lines. Compared to matched adjacent normal tissues, CC tissues showed higher SNORD16 expression levels, and no correlation was found between SNORD16 and RPL4. Patients with high SNORD16 expression levels had a worse prognosis, and multivariate analysis showed the high SNORD16 expression was an independent prognostic factor for CC. In vitro gain- and loss-of-function studies revealed that SNORD16 can promote cell growth, proliferation, migration, and invasion of CC cells by inhibiting apoptosis. These results suggested that SNORD16 has an oncogenic role in CC and might be a novel diagnostic and prognostic biomarker for CC.

13.
Sci Total Environ ; 736: 139695, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32497885

RESUMO

Nitrosamines, as a class of emerging frequently detected nitrogenous disinfection byproducts (N-DBPs) in drinking water, have gained increasing attention due to their potentially high health risk. Few studies focus on the occurrence variation and carcinogenic health risk of nitrosamines in drinking water systems. Our study aimed to investigate the spatial and temporal variability of nitrosamines in a drinking water system and to conduct a carcinogenic health risk assessment. Three types of water samples, including influent water, treated water and tap water, were collected monthly during an entire year in a drinking water system utilizing a combination of chlorine dioxide and chlorine in central China, and 9 nitrosamines were measured. The nitrosamine formation potentials (FPs) in influent water were also determined. N-nitrosodimethylamine (NDMA) was the most prevalent compound and was dominant in the water samples with average concentrations ranging from 2.5 to 67.4 ng/L, followed by N-nitrosodiethylamine (NDEA) and N-nitrosopiperidine (NPIP). Nitrosamine occurrence varied monthly, and significant seasonal differences were observed in tap water (p < .05). There were decreasing mean NDMA, NDEA and NPIP concentrations from influent water to treated water to tap water, but no significant spatial variability was observed within the water distribution system (p > .05). The average and 95th percentile total lifetime cancer risks for the three main nitrosamines were 4.83 × 10-5 and 4.48 × 10-4, respectively, exceeding the negligible risk level (10-6) proposed by the USEPA. Exposure to nitrosamines in drinking water posed a higher cancer risk for children than for adults, and children aged 0.75 to 1 years suffered the highest cancer risk. These results suggest that nitrosamine occurrence in tap water varied temporally but not spatially. Exposure to drinking water nitrosamines may pose a carcinogenic risk to human health, especially to children.


Assuntos
Água Potável/análise , Nitrosaminas/análise , Poluentes Químicos da Água/análise , Purificação da Água , Criança , China , Humanos , Lactente , Medição de Risco
14.
Environ Int ; 137: 105518, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32018134

RESUMO

BACKGROUND: Toxicological studies have demonstrated that disinfection by-products (DBPs) can induce oxidative stress, a proposed mechanism that is relevant to adverse birth outcomes. OBJECTIVE: To examine the associations of blood trihalomethanes (THMs) and urinary haloacetic acids (HAAs) with urinary biomarkers of oxidative stress among pregnant women. METHODS: From 2015 to 2017, a total of 4150 blood and 4232 urine samples were collected from 1748 Chinese women during pregnancy. We determined concentrations of 4 blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and 2 urinary HAAs [dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)]. The summary measures of exposure for brominated THMs (Br-THMs; a molar sum of BDCM, DBCM, and TBM) and total THMs (TTHMs; a molar sum of TCM and Br-THMs) were also calculated. Associations of categorical (i.e., tertiles) and continuous measures of DBPs with urinary concentrations of oxidative stress (OS) biomarkers, 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), and 8-iso-prostaglandin F2α (8-isoPGF2α), were assessed using linear mixed regression models. RESULTS: After adjusting for relevant confounding factors, we observed positive dose-response relationships between blood Br-THM tertiles and urinary HNE-MA (P for trend < 0.001). We also found positive associations between tertiles of blood TCM and TTHMs and urinary 8-OHdG and HNE-MA (all P for trend < 0.05). Urinary HAAs were also positively associated with 8-OHdG, HNE-MA, and 8-isoPGF2α in a dose-response manner (all P for trend < 0.001). These associations were further confirmed when we modeled DBP exposures as continuous variables in linear mixed regression models, as well as in penalized regression splines based on generalized additive mixed models. CONCLUSIONS: Exposure to DBPs during pregnancy may increase maternal OS status.


Assuntos
Desinfetantes , Estresse Oxidativo , Efeitos Tardios da Exposição Pré-Natal , Ácido Tricloroacético , Trialometanos , Poluentes Químicos da Água , Biomarcadores , Desinfecção , Feminino , Humanos , Gravidez , Trialometanos/sangue
15.
Chemosphere ; 246: 125805, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31918106

RESUMO

BACKGROUND: Bisphenol A (BPA) has been shown to affect normal fetal growth, but human evidence on its analogues (BPF and BPS) is limited. OBJECT: To examine the associations between prenatal exposure to BPA and its analogues (BPF and BPS) and ultrasound parameters of fetal growth. METHODS: We measured urinary BPA, BPF, and BPS concentrations among 322 pregnant women during late pregnancy from a cohort study in Wuhan, China. Fetal biparietal diameter (BPD), head circumference (HC), femur length (FL), and abdominal circumference (AC) were measured by ultrasonography. The associations of maternal urinary BPA, BPF, and BPS concentrations with ultrasound parameters of fetal growth were estimated by multivariable adjusted models. RESULTS: We observed a gender difference in association of maternal urinary BPA concentrations and fetal HC (P for interaction = 0.003); each ln-unit increase in maternal urinary BPA concentration was associated with a mean decrease of 0.10 cm (95%CI: 0.18, -0.02) among boys and a mean increase of 0.14 cm (95%CI: 0.00, 0.28) among girls for HC. The associations were robust for urinary BPA concentrations modeled as tertiles or including urinary BPA, BPF, and BPS into mutual adjustment models. We did not observe robust associations between maternal urinary BPF and BPS concentrations and ultrasound parameters of fetal growth, though an inverse association with AC and a positive association with FL were estimated for maternal urinary BPF concentrations modeled as continuous variables. CONCLUSIONS: Prenatal exposure to BPA but not BPF and BPS was sex-specifically associated with certain fetal growth parameters.


Assuntos
Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Exposição Materna/estatística & dados numéricos , Fenóis/toxicidade , Compostos Benzidrílicos/metabolismo , China , Estudos de Coortes , Poluentes Ambientais/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Fenóis/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ultrassonografia , Vitaminas
16.
Environ Int ; 134: 105335, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783240

RESUMO

BACKGROUND: Trihalomethanes (THMs) have demonstrated adverse effects on male reproductive systems in experimental animals, but human evidence has been inconsistent. Prior researches have been limited by small sample sizes and inadequate exposure assessment. OBJECTIVES: To investigate the association between blood THMs and repeated measurements of semen quality parameters among 1199 healthy men screened as potential sperm donors. METHODS: We recruited healthy men presenting to the Hubei Province Human Sperm Bank from April to December 2017. At study entry, each participant provided a spot blood sample which was used to quantify blood concentrations of four THMs: chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM). The summary measures of exposure for brominated THMs (Br-THMs; molar sum of BDCM, DBCM and TBM) and total THMs (TTHMs; molar sum of TCM and Br-THMs) were also calculated. We used multivariable linear regression models to estimate the cross-sectional associations of tertiles of blood THM concentrations with semen quality parameters measured at study entry, and mixed-effect models to estimate the longitudinal associations accounting for repeated measures of semen quality, adjusting for relevant confounding factors. RESULTS: In the cross-sectional analysis, several inverse dose-response relationships were observed across tertiles of blood TCM concentrations and sperm count, total motility and progressive motility, and between blood DBCM, and Br-THMs, and TTHMs and sperm count and concentration. The inverse associations of blood TCM, DBCM, Br-THMs and TTHMs with sperm count were confirmed in the longitudinal, repeated measure analysis. CONCLUSION: Our results suggest that exposure to THMs from drinking water may be related to decreased semen quality in young healthy men.


Assuntos
Água Potável/química , Análise do Sêmen , Trialometanos/sangue , Poluentes Químicos da Água/sangue , China , Estudos Transversais , Humanos , Masculino , Espermatozoides/efeitos dos fármacos , Trialometanos/efeitos adversos , Poluentes Químicos da Água/efeitos adversos
17.
J Hazard Mater ; 384: 121431, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31672436

RESUMO

Spermatogenesis-related microRNAs (miRNAs) are vulnerable to polycyclic aromatic hydrocarbons (PAHs). Changes in spermatogenesis-related miRNAs may be biological intermedia in mechanisms linking PAHs and semen quality. This study aimed to investigate whether spermatogenesis-related microRNAs mediate the associations between PAHs and semen quality. We measured 10 monohydroxylated PAHs (OH-PAHs) in repeated urine samples and three candidate spermatogenesis-related miRNAs (miRNA106a, miRNA21, and miRNA34c) in seminal plasma from men attending an infertility clinic (n = 111). Mediation analysis was applied to determine the mediating role of spermatogenesis-related miRNAs in the association of PAH exposure with semen quality. Urinary 2-OHFlu and 2-OHPh were related to reduced seminal plasma miRNA34c (p for trend = 0.05 and 0.03, respectively). Urinary 9-OHPh was related to reduced seminal plasma miR106a (p for trend = 0.02), which in turn, was positively associated with sperm concentration, sperm count, sperm total motility, and progressive motility (all p for trends<0.05). Up to 43.8% of the eff ;ect of urinary 9-OHPh on decreased sperm concentration was mediated by seminal plasma miR106a. Our results suggested that certain PAH exposure was associated with reduced spermatogenesis-related miRNAs and such alterations might be an intermediate mechanism by which PAHs exert its adverse effects on semen quality.


Assuntos
Poluentes Ambientais/urina , Infertilidade Masculina/genética , MicroRNAs/análise , Hidrocarbonetos Policíclicos Aromáticos/urina , Sêmen/química , Espermatogênese/genética , Adulto , Exposição Ambiental/análise , Clínicas de Fertilização , Humanos , Masculino , Projetos Piloto , Análise do Sêmen
18.
Environ Res ; 179(Pt A): 108778, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31629946

RESUMO

BACKGROUND: Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans. OBJECTIVE: To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men. METHOD: Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers. RESULTS: Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend<0.05), except for monoethyl phthalate (MEP) in relation to HNE-MA. Additionally, significantly or suggestively inverse dose-dependent relationships were exhibited between urinary 8-isoPGF2α and sperm concentration (p for trend = 0.05), and between urinary 8-OHdG and percent of normal sperm morphology (p for trend = 0.01). Mediation analysis showed that urinary 8-isoPGF2α suggestively mediated 12% of the inverse association between monobutyl phthalate (MBP) and sperm concentration, and that urinary 8-OHdG suggestively mediated 32% of the inverse association of MEP with percent of normal sperm morphology (both p < 0.10). CONCLUSIONS: Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Ácidos Ftálicos/metabolismo , Análise do Sêmen , Sêmen/efeitos dos fármacos , Adulto , Animais , China , Poluentes Ambientais/toxicidade , Humanos , Masculino , Estresse Oxidativo , Ácidos Ftálicos/toxicidade , Reprodução , Contagem de Espermatozoides
19.
Environ Sci Technol ; 53(20): 12026-12034, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525872

RESUMO

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.


Assuntos
Citocromo P-450 CYP2E1 , Efeitos Tardios da Exposição Pré-Natal , Biomarcadores , Peso ao Nascer , Desinfecção , Feminino , Glutationa Transferase , Humanos , Exposição Materna , Polimorfismo Genético , Gravidez , Trialometanos
20.
Environ Int ; 129: 354-363, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31150977

RESUMO

BACKGROUND: A growing body of evidence has found links between endocrine disruptor phthalates and male reproductive disorders, but the mechanisms underlying these relationships are poorly known. Seminal plasma metabolomes may mediate associations of phthalate exposure with impaired semen quality. OBJECTIVE: To identify seminal plasma metabolomes associated with poor semen quality and evaluate their associations with urinary phthalate metabolites among 660 Chinese adult men. METHOD: The seminal plasma metabolic profiles were acquired using an untargeted approach based on liquid chromatography-high resolution mass spectrometry. We explored the differences in seminal plasma metabolites between participants with poor and good semen quality and evaluated cross-sectional associations between discriminatory metabolic biomarkers and urinary phthalate metabolites. RESULTS: Differences between poor and good semen quality groups were observed in relation to 25 seminal plasma metabolites, mostly related to the metabolism of polyunsaturated fatty acids (PUFA) and acylcarnitine (all p < 0.05). After adjusting for various confounders and multiple tests, metabolites were all significantly associated with one or more individual sperm quality parameters (motility, concentration, total count, and morphology) (all p < 0.05). Among identified metabolic biomarkers, seminal plasma L-palmitoylcarnitine, linoelaidyl carnitine, and oleic acid were inversely associated with urinary mono-(2-ethylhexyl) phthalate (MEHP), and seminal plasma L-acetylcarnitine was inversely associated with the proportion of di-(2-ethylhexyl)-phthalate metabolites (DEHP) excreted as MEHP in urine (%MEHP) (all p < 0.05). Mediation analysis revealed that oleic acid and L-acetylcarnitine mediated significant proportions (6.7% and 17%, respectively) of the positive associations between urinary DEHP metabolites and the percentage of spermatozoa with an abnormal head. CONCLUSIONS: Elevated urinary phthalate metabolites may impact semen quality by causing metabolic disorders of seminal plasma PUFAs and acylcarnitine. These pathways warrant further investigation.


Assuntos
Metaboloma , Ácidos Ftálicos/urina , Sêmen/metabolismo , Adulto , Carnitina/análogos & derivados , Carnitina/urina , Cromatografia Líquida , Estudos Transversais , Dietilexilftalato/metabolismo , Humanos , Masculino , Análise do Sêmen , Espermatozoides/metabolismo , Espectrometria de Massas em Tandem
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