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Organochlorine pesticides (OCPs) are endocrine-disrupting chemicals and may alter male reproductive hormone concentrations.To explore the associations between multiple OCP exposures and serum testosterone concentrations among Chinese men.We investigated 421 men who provided serum samples from an infertility clinic in Wuhan, China. Each man completed a questionnaire concerning demographic characteristics and lifestyle habits. Serum concentrations of 18 OCPs and total testosterone were measured. Linear regression models were used to explore whether serum OCP levels were associated with altered testosterone concentrations, and potential effect modifications by age and body mass index (BMI) were also examined.After adjusting for potential confounders, elevated dieldrin and p,p'-DDD levels had monotonically negative and positive exposure-response associations with testosterone concentrations, respectively (-30.98 ng/dL, 95% CI: -72.34, 10.37; P for trend = 0.12 and 41.31 ng/dL, 95% CI: -0.32, 82.93; P for trend = 0.06 for the highest vs. non-detectable exposure category, respectively). After stratification by age and BMI, dieldrin in relation to decreased testosterone concentrations was more pronounced among men aged30 years old, and p,p'-DDD in relation to increased testosterone concentrations was stronger among men aged ≥30 years old and among men with a BMI24 kg/mThe study found evidence that serum dieldrin and p,p'-DDD concentrations might be associated with altered serum testosterone concentrations.

Prenatal exposure to metals has been linked with adverse pregnancy outcomes. Oxidative stress and epigenetic changes are potential mechanisms of action.We aimed to examine the associations of individual and mixtures of metal exposures with oxidative stress and DNA methylation among pregnant women.We measured a panel of 16 metals and 3 oxidative stress biomarkers including 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-isoprostaglandin F2α (8-isoPGF2α) in urine from 113 pregnant women in a Chinese cohort. Biomarkers of global DNA methylation including Alu and long interspersed nucleotide element-1 (LINE-1) in cord blood were measured. Multivariable linear regression and Bayesian kernel machine regression (BKMR) models were separately applied to estimate the associations between individual and mixtures of metal exposures and biomarkers of oxidative stress and global DNA methylation.In single-metal analyses, we observed positive associations between 11 metals [arsenic (As), cadmium (Cd), thallium (Tl), barium (Ba), nickel (Ni), vanadium (V), cobalt (Co), zinc (Zn), copper (Cu), selenium (Se) and molybdenum (Mo)] and at least one of oxidative stress biomarkers (all FDR-adjusted P-values0.05). In mixture analyses, we found positive overall associations of metal mixtures with 8-OHdG and 8-isoPGF2α, and Se was the most important predictor. There was no evidence on associations of urinary metals as individual chemicals and mixtures with Alu and LINE-1 methylation.Urinary metals as individual chemicals and mixtures were associated with increased oxidative stress, especially Se.

Prior human studies have explored effects of phthalate exposures on thyroid function, but the underlying biological mechanisms remain poorly unclear. We aimed to explore the associations between phthalate exposures and thyroid function among a potentially susceptible population such as patients with thyroid nodules, and further to assess the mediating role of oxidative stress. We measured eight phthalate metabolites, three oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine and three thyroid function biomarkers [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)] in serum among 214 patients with thyroid nodules. Multivariate regression models were applied to assess the associations among urinary phthalate metabolites, oxidative stress and thyroid function biomarkers. The potential mediating role of oxidative stress was explored by mediation analysis. We observed that multiple urinary phthalate metabolites were associated with altered FT4 and increased oxidative stress biomarkers (all FDR-adjusted P ≤ 0.05). Meanwhile, we found that 8-isoPGF2α was negatively associated with FT3/FT4 among patients with benign thyroid nodules (FDR-adjusted P = 0.08). The mediation analysis indicated that 8-isoPGF2α mediated the associations of urinary MEHHP and %MEHP with FT3/FT4, with 55.6% and 32.6% proportion of the mediating effects, respectively. Our data suggest that lipid peroxidation may be an intermediate mechanism involved in the effects of certain phthalate exposures on altered thyroid function among patients with benign thyroid nodules.

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). 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.

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.

Background Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers. Methods Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 μm (PM2.5) and ≤10 μm (PM10), and nitrogen dioxide (NO2) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function. Results Prenatal exposures to PM2.5, PM10, and NO2 during early pregnancy were negatively associated with %CD3+ and %CD3+CD8+ cells, and during late pregnancy were positively associated with %CD3+ cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex. Conclusions Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.

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.

Epigenetic mechanisms, such as altered DNA methylation, may participate in the relationship between prenatal phthalate exposure and adverse birth outcomes.To explore the mediation effect of DNA methylation in the associations of phthalate exposure before delivery with birth outcomes in a Chinese cohort.Eight phthalate metabolites in maternal urine before delivery and DNA methylation of Alu and long interspersed nucleotide elements (LINE-1) in cord blood were determined among 106 mother-infant pairs. General additive models were used to assess the associations of maternal urinary phthalate metabolites with birth outcomes and DNA methylation; the mediating role of DNA methylation in cord blood was evaluated by mediation analysis.We found sex-specific associations between prenatal phthalate exposure and birth outcomes and DNA methylation of cord blood. For example, the molar sum of di-2-(ethylhexyl) phthalate (∑DEHPm) metabolites in maternal urine was positively associated with gestational age among male newborns only (P 0.05); maternal urinary monobenzyl phthalate (MBzP) was negatively associated with Alu methylation among female newborns only (P 0.05). Mediation analysis did not find that methylation of Alu and LINE-1 to be a direct mediator in the relationships between maternal urinary phthalate metabolites before delivery and birth outcomes.Prenatal exposure to certain phthalates was associated with altered birth outcomes and decreased repetitive element methylation of newborns. However, the altered birth outcomes exerted by prenatal phthalate exposure does not seem to be directly mediated through repetitive element methylation in cord blood.

Studies have documented that exposure to organochlorine pesticides (OCPs) is linked with breast cancer, but the underlying biological mechanisms are still unknown. This study included 313 women diagnosed with breast cancer and 313 controls in Wuhan, China, and measured 18 OCPs in serum and 3 oxidative stress biomarkers in urine. Multivariable adjusted regression models were used to evaluate the associations among OCPs, oxidative stress biomarkers, and breast cancer. The mediating effect of oxidative stress was assessed by mediation analysis. We observed that most OCPs were positively associated with risk of breast cancer (all FDR-P values 0.05 or 0.10). Moreover, we found that p,p'-DDT, p,p'-DDD, dieldrin, heptachlor, and heptachlor epoxide were positively associated with 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-iso-prostaglandin F

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.

Epidemiological studies have suggested that phthalate exposures were associated with adverse reproductive outcomes, such as low oocyte yield and reduced embryo quality, but the underlying mechanisms remained largely unknown. Oxidative stress may be a potential contributor to phthalate-induced adverse reproductive outcomes. To explore the associations between phthalate exposure and levels of oxidative stress among women seeking in vitro fertilization (IVF), we measured the concentrations of eight phthalate metabolites and biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and total antioxidant capacity (TAC), in follicular fluid (FF) samples collected from 332 women. Multivariable linear regression models were used to assess the associations between phthalate metabolites and biomarkers of oxidative stress in FF samples. The concentrations of most tested phthalate metabolites were positively associated with the 8-OHdG levels. The metabolites of di-(2-ethylhexyl) phthalate (DEHP) were inversely associated with the TAC levels. The concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) were positively associated with the MDA levels. Our results revealed a positive association between phthalate metabolites and oxidative stress levels in FF, while more toxicological and epidemiological studies are required to confirm our findings.

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.

Phthalates have been reported to affect the function and growth of thyroid. However, there is little data on the effect of phthalates on thyroid oncogenesis. Here we explored the associations between phthalates exposure and the risks of thyroid cancer and benign nodule. We sex-matched 144 thyroid cancer, 138 benign nodule patients and 144 healthy adults from Wuhan, China. Eight phthalate metabolites in spot urine samples were quantified using high-performance liquid chromatography and tandem mass spectrometry. The associations of creatinine-corrected urinary phthalate metabolites with the risks of thyroid cancer and benign nodule were assessed using multivariable logistic regression models. We found that urinary monomethyl phthalate (MMP), mono(2-ethyl-5hydroxyhexyl) phthalate (MEHHP) and mono(2-ethylhexyl) phthalate (MEHP) associated with increased risks of thyroid cancer and nodule, with adjusted odds ratios (ORs) ranging from 1.74 to 4.78 comparing the extreme tertiles, and urinary monobutyl phthalate (MBP) was associated with decreased risks of thyroid cancer and benign nodule (all P for trends 0.05). Male-specific positive associations of urinary monoethyl phthalate (MEP) with thyroid cancer and nodule as well as urinary mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) with thyroid cancer were also observed. Our results suggest that exposure to certain phthalates may contribute to increased risks of thyroid cancer and benign nodule.