Zhijun Zhou

Paraquat inhibits cell viability via enhanced oxidative stress and apoptosis in human neural progenitor cells

Paraquat (PQ) is one of the most widely used herbicides in the world. Although available evidence indicates that people exposed to PQ have a higher risk of developing Parkinsons disease, adverse effects of PQ on neural progenitor cells have not been investigated yet. In this study, we investigated the in vitro effect of PQ on immortalized human embryonic neural progenitor cells (hNPCs) by treating them with various concentrations of PQ (0, 0.1, 1, 10 and 100 μM) for 24h. We show that PQ treatment reduces the cell viability and proliferation and induces reactive oxygen species (ROS) production in a dose-dependent manner. In addition, apoptosis induced by PQ was significantly increased at a concentration of as low as 1 μM. To illustrate the underlying molecular mechanisms, we examined the caspase-3 activity, intracellular calcium level, the NF-κB activity, as well as expression of p21, p53 and metallothionein-III mRNA. PQ significantly increased caspase-3 activity at the concentration of 100 μM. Similarly, PQ triggered intracellular Ca(2+) releases and activation of NF-κB was observed after exposure of hNPCs at low concentrations of PQ (1 μM). Meanwhile, p53 and p21 mRNA transcripts were significantly up-regulated at 10 μM and 1 μM of PQ, respectively. MT-III mRNA and protein expression was significantly up-regulated at 1 μM of PQ and reached peak at 10 μM. These results suggest that PQ could reduce viability of hNPCs by inducing oxidative stress and apoptosis.

Urine bisphenol-A (BPA) level in relation to semen quality

OBJECTIVE To determine whether urine bisphenol-A (BPA) levels are associated with lower semen quality. DESIGN Cohort study. SETTING Four regions in China where high exposure to BPA in the workplace existed. PATIENT(S) 218 men with and without BPA exposure in the workplace. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Semen parameters. RESULT(S) After adjustment for potential confounders using linear regression, increasing urine BPA level was statistically significantly associated with [1] decreased sperm concentration, [2] decreased total sperm count, [3] decreased sperm vitality, and [4] decreased sperm motility. Compared with men who did not have detectable urine BPA levels, those with detectable urine BPA had more than three times the risk of lowered sperm concentration and lower sperm vitality, more than four times the risk of lower sperm count, and more than twice the risk of lower sperm motility. The urine BPA level was not associated with semen volume or abnormal sperm morphology. Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population. Despite a markedly reduced sample size, the inverse correlation between increased urine BPA levels and decreased sperm concentration and total sperm count remained statistically significant. CONCLUSION(S) These results provide the first epidemiologic evidence of an adverse effect of BPA on semen quality.

Occupational exposure to bisphenol-A (BPA) and the risk of Self-Reported Male Sexual Dysfunction

BACKGROUND Animal studies have suggested that bisphenol-A (BPA) is a potential human endocrine disrupter; but evidence from human studies is needed. METHODS We conducted an occupational cohort study to examine the effect of occupational exposure to BPA on the risk of male sexual dysfunction. Current workers from BPA-exposed and control factories were recruited. The exposed workers were exposed to very high BPA levels in their workplace. Male sexual function was ascertained through in-person interviews using a standard male sexual function inventory. RESULTS BPA-exposed workers had consistently higher risk of male sexual dysfunction across all domains of male sexual function than the unexposed workers. After controlling for matching variables and potential confounders, exposed workers had a significantly increased risk of reduced sexual desire [odds ratios (OR) = 3.9, 95% confidence interval: 1.8-8.6), erectile difficulty (OR = 4.5, 95% CI 2.1-9.8), ejaculation difficulty (OR = 7.1, 95% CI 2.9-17.6), and reduced satisfaction with sex life (OR = 3.9, 95% CI 2.3-6.6). A dose-response relationship was observed with an increasing level of cumulative BPA exposure associated with a higher risk of sexual dysfunction. Furthermore, compared with the unexposed workers, BPA-exposed workers reported significantly higher frequencies of reduced sexual function within 1 year of employment in the BPA-exposed factories. CONCLUSIONS Our findings provide the first evidence that exposure to BPA in the workplace could have an adverse effect on male sexual dysfunction.

Bisphenol A levels in blood and urine in a Chinese population and the personal factors affecting the levels

The objective of the study was to describe the background bisphenol A (BPA) levels in urine and serum of a Chinese population without occupational exposure and to examine the personal characteristics influencing these levels. Workers from 10 factories and their family members were recruited and their peripheral blood and spot urine samples were collected. The conjugated and free BPA of the samples was assayed with high-performance liquid chromatography. The exposure levels were checked with 2-independent-samples test, and the potential personal factors influencing exposure levels were analyzed using nonlinear correlation. Of the total of 952 subjects participating in the study, urine and blood samples were taken from 97% and 93% of them, respectively. The detectable rates were 50% for urine samples and 17% for serum samples, given the detection limit of 0.31 microg/L for urine and 0.39 microg/L for serum. The arithmetic mean (AM) and geometric mean (GM) of non-creatinine-adjusted urinary BPA level were 10.45 and 0.87 microg/L, which became 24.93 and 0.38 microg/g Cr after the creatinine level was adjusted; serum BPA levels were 2.84 microg/L (AM) and 0.18 microg/L (GM). Males and those with smoking habit had higher biological burden of BPA. The results indicated that half of the study subjects had detectable BPA in their urine samples. BPA levels were influenced by gender and smoking status. The sources of non-occupational BPA exposures should be explored.

Effects of Prenatal Exposure to Coal-Burning Pollutants on Children’s Development in China

Background Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs), lead, and mercury are released by combustion of coal and other fossil fuels. Objectives In the present study we evaluated the association between prenatal exposure to these pollutants and child development measured by the Gesell Developmental Schedules at 2 years of age. Methods The study was conducted in Tongliang, Chongqing, China, where a seasonally operated coal-fired power plant was the major source of ambient PAHs and also contributed lead and mercury to the air. In a cohort of nonsmoking women and their newborns enrolled between March 2002 and June 2002, we measured levels of PAH–DNA adducts, lead, and mercury in umbilical cord blood. PAH–DNA adducts (specifically benzo[a]pyrene adducts) provided a biologically relevant measure of PAH exposure. We also obtained developmental quotients (DQs) in motor, adaptive, language, and social areas. Results Decrements in one or more DQs were significantly associated with cord blood levels of PAH–DNA adducts and lead, but not mercury. Increased adduct levels were associated with decreased motor area DQ (p = 0.043), language area DQ (p = 0.059), and average DQ (p = 0.047) after adjusting for cord lead level, environmental tobacco smoke, sex, gestational age, and maternal education. In the same model, high cord blood lead level was significantly associated with decreased social area DQ (p = 0.009) and average DQ (p = 0.038). Conclusion The findings indicate that exposure to pollutants from the power plant adversely affected the development of children living in Tongliang; these findings have implications for environmental health policy.

Urine bisphenol-A level in relation to obesity and overweight in school-age children.

Bisphenol-A (BPA) is a potential endocrine disruptor impacting metabolic processes and increasing the risk of obesity. To determine whether urine BPA level is associated with overweight/obesity in school-age children, we examined 1,326 students in grades 4–12 from three schools (one elementary, one middle, and one high school) in Shanghai. More than 98% of eligible students participated. Total urine BPA concentration was measured and anthropometric measures were taken by trained research staff. Information on risk factors for childhood obesity was collected for potential confounders. Age- and gender-specific weight greater than 90th percentile of the underlying population was the outcome measure. After adjustment for potential confounders, a higher urine BPA level (≥2 µg/L), at the level corresponding to the median urine BPA level in the U.S. population, was associated with more than two-fold increased risk of having weight >90th percentile among girls aged 9–12 (adjusted odds ratio (aOR) = 2.32, 95% confidence interval: 1.15–4.65). The association showed a dose-response relationship with increasing urine BPA level associated with further increased risk of overweight (p = 0.006 for trend test). Other anthropometric measures of obesity showed similar results. The same association was not observed among boys. This gender difference of BPA effect was consistent with findings from experimental studies and previous epidemiological studies. Our study suggests that BPA could be a potential new environmental obesogen. Widespread exposure to BPA in the human population may also be contributing to the worldwide obesity epidemic.

Relationship Between Urine Bisphenol-A Level and Declining Male Sexual Function

The adverse effect of bisphenol-A (BPA) on the male reproductive system observed in animal studies has not been well examined in human populations. BPA is potentially a serious public health problem because of its widely detected presence in the human body. This study was conducted among 427 male workers in regions where high levels of BPA exposure existed. All participants provided urine samples, which were tested for BPA concentration using high-performance liquid chromatography. Male sexual dysfunction was ascertained using standard male sexual function inventories. Male sexual dysfunction was measured in 4 domains using 7 indices. After controlling for potential confounders using linear regression, increasing urine BPA level was associated with worsening male sexual function on a continuous scale. All 7 indices demonstrated this negative linear correlation. Increasing urine BPA level was associated with decreased sexual desire (P < .001), more difficulty having an erection (P < .001), lower ejaculation strength (P < .001), and lower level of overall satisfaction with sex life (P < .01). A similar negative correlation was also observed among participants exposed to BPA from only environmental sources (no occupational exposure to BPA), although the estimates in this group were less stable because of a smaller sample size. Our results reveal a correlation between a biological measure of urine BPA level and declining male sexual function. This finding may enhance the understanding of the BPA effect in human populations, and may have important public health implications given the widespread human exposure to BPA.

Benefits of reducing prenatal exposure to coal-burning pollutants to children's neurodevelopment in China.

Background Coal burning provides 70% of the energy for China’s industry and power, but releases large quantities of polycyclic aromatic hydrocarbons (PAHs) and other pollutants. PAHs are reproductive and developmental toxicants, mutagens, and carcinogens. Objective We evaluated the benefit to neurobehavioral development from the closure of a coal-fired power plant that was the major local source of ambient PAHs. Methods The research was conducted in Tongliang, Chongqing, China, where a coal-fired power plant operated seasonally before it was shut down in May 2004. Two identical prospective cohort studies enrolled nonsmoking women and their newborns in 2002 (before shutdown) and 2005 (after shutdown). Prenatal PAH exposure was measured by PAH–DNA adducts (benzo[a]pyrene–DNA) in umbilical cord blood. Child development was assessed by the Gesell Developmental Schedules at 2 years of age. Prenatal exposure to other neurotoxicants and potential confounders (including lead, mercury, and environmental tobacco smoke) was measured. We compared the cohorts regarding the association between PAH–DNA adduct levels and neurodevelopmental outcomes. Results Significant associations previously seen in 2002 between elevated adducts and decreased motor area developmental quotient (DQ) (p = 0.043) and average DQ (p = 0.047) were not observed in the 2005 cohort (p = 0.546 and p = 0.146). However, the direction of the relationship did not change. Conclusion The findings indicate that neurobehavioral development in Tongliang children benefited by elimination of PAH exposure from the coal-burning plant, consistent with the significant reduction in PAH–DNA adducts in cord blood of children in the 2005 cohort. The results have implications for children’s environmental health in China and elsewhere.

Urinary pyrethroid metabolites among pregnant women in an agricultural area of the Province of Jiangsu, China.

Pyrethroid pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Of particular concern is exposure of pregnant women and their fetuses because little is known about the potential developmental hazards of such exposure. Several studies have detected internal pyrethroid exposure in urine both in adults and children, but few published data are available on metabolites in pregnant women. The present paper provides data on pyrethroid pesticides exposure based on questionnaire items and measurement of maternal urinary metabolite levels among 1149 pregnant women living in agricultural area of Jiangsu Province, China in 2009-2010, none of which reported occupational exposure to pyrethroid insecticides during pregnancy. To assess exposure to pyrethroid pesticides, urine specimens were analyzed for three main metabolites of 3-phenoxybenzoic acid (3-PBA), cis-and-trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA) using a gas chromatography-mass spectrometry method. The limits of detection for three pyrethroid metabolites were 0.1μg/L. All pyrethroid metabolites were found in more than 94.0% of the urine samples. Median unadjusted and creatinine-adjusted values for urinary pyrethroid metabolites in these females were 1.01μg/L and 1.55μg/g Cre for 3-PBA, 0.44μg/L and 0.69μg/g Cre for cis-DCCA, 1.17μg/L and 1.86μg/g Cre for trans-DCCA, respectively. About half (45.5%) of women reported that they or family members had applied commercially available indoor insecticides during pregnancy. Both the questionnaire and laboratory data revealed that exposure to pyrethroid pesticides was considerably widespread in our subjects. The median values of urinary metabolites in the present study were about 4-10 times higher as those of general population from the developed countries. Interestingly, we found there was a temporal season variation tendency in different months. Especially, the levels of urinary metabolites in summer were significant higher than those in winter. These data indicated the need to assess the potential adverse effects of pyrethroid pesticides exposure on fetuses and infants in order to take adequate measures to protect pregnant women from pesticide exposures during pregnancy.

Occupational Exposure Levels of Bisphenol A among Chinese Workers

Occupational Exposure Levels of Bisphenol A among Chinese Workers: Yonghua He, et al. School of Public Health/WHO Collaborating Center for Occupational Health, Fudan University, PR China