Yijun Zhou

Prenatal low-level mercury exposure and neonatal anthropometry in rural northern China.

Mercury (Hg) is a ubiquitous heavy metal that can negatively affect human health; however, few studies have examined the impact of prenatal low-level Hg exposure on fetal growth. We investigated prenatal exposure levels of Hg and the relationship between Hg levels and neonatal anthropometrics, including birth weight, length, and head circumference. A total of 258 mother-infant pairs were recruited from a rural community located on the southern coastal area of Laizhou Bay of the Bohai Sea in northern China between September 2010 and December 2011. We measured maternal and cord whole blood Hg levels and examined their association with neonatal anthropometrics. The geometric means (GMs) of Hg in maternal and cord whole blood were 0.84μgL(-1) and 1.46μgL(-1), respectively. The Hg exposure levels in our study population were much lower than those reported in previous domestic studies. No significant associations were found between maternal or cord blood Hg levels and birth weight, length, and head circumference. However, our results should be interpreted with caution given the high toxicity of Hg and its persistence in the body. Studies focusing on long-term adverse outcomes are needed to further examine the cumulative effects of low-level Hg exposure.

Association between prenatal exposure to polybrominated diphenyl ethers and young children's neurodevelopment in China.

The use of polybrominated diphenyl ethers (PBDEs) has been dramatically increasing over the last two decades in China. Animal studies suggest that prenatal exposure to PBDEs may result in neurodevelopmental deficits. Two hundred thirty-two participating mothers were recruited from a prospective birth cohort in rural northern China between September 2010 and February 2012. We analyzed 232 cord blood specimens for selected PBDE congeners and examined their association with childrens developmental quotients (DQs) at 12 (n=192) and 24 (n=149) months of age based on the Gesell Developmental Schedules (motor, adaptive, language, and social domains). There were no substantial differences by demographic characteristics among the three time points: baseline, 12 and 24 months of age. Median cord blood levels of PBDE congeners 47, 99, 100, and 153 were 3.71, 6.70, 2.63, and 2.19 ng/g lipid, respectively. At 12 months of age, neither the individual nor total (the sum of BDEs 47, 99, 100, and 153) congener levels were associated with any of the four domain DQs. However, at 24 months of age, a 10-fold increase in BDE-99 levels was associated with a 2.16-point decrease [95% confidence interval (CI): -4.52, -0.20] in language domain DQs and a 10-fold increase in BDE-47 levels was associated with a 1.89-point decrease (95% CI: -3.75, -0.03) in social domain DQs. Prenatal exposure to PBDEs was associated with lower DQs in young children. The results contribute to the growing evidence that PBDEs could act as developmental neurotoxicants,and the findings have implications for childrens environmental health in China.

Prenatal exposure to pyrethroid insecticides and birth outcomes in Rural Northern China

Although pyrethroid insecticides are widely used, little is known about potential adverse effects on fetal growth. Participating 454 mother–infant pairs were recruited from a prospective birth cohort in rural northern China between September 2010 and 2012. We measured five non-specific pyrethroid metabolites in maternal urine at delivery and examined their association with birth outcomes including birth weight, length, head circumference, and gestational duration. The creatinine-adjusted medians of pyrethroid metabolites in urine were 0.51 μg/g for cis-DCCA, 0.65 μg/g for trans-DCCA, and 0.68 μg/g for 3-PBA. The pregnant women had substantially higher levels of urinary pyrethroid metabolites compared with those reported in developed countries. A increase in total (the sum of cis-DCCA, trans-DCCA, and 3-PBA) but not individual urinary metabolite levels was associated with a decrease in birth weight (adjusted β=–96.76 g per log10 unit increase, 95% confidence interval=–173.15 to –20.37). No associations were found between individual or total metabolite levels and birth length, head circumference, or gestational duration. We report an adverse association of prenatal exposure to pyrethroids as measured by urinary metabolites with birth weight. More studies are warranted in China given the relatively high levels of urinary metabolites in our study population.

Carbon disulfide induces rat testicular injury via mitochondrial apoptotic pathway

Carbon disulfide (CS2), one of the most important volatile organic chemicals, was shown to have serious impairment to male reproductive system. But the underline mechanism is still unclear. In the present study, we aim to investigate the male germ cell apoptosis induced by CS2 exposure alone and by co-administration with cyclosporin A (CsA), which is the inhibitor of membrane permeability transition pore (MPTP). It was shown that CS2 exposure impaired ultrastructure of germ cells, increased the numbers of apoptotic germ cells, accumulated intracellular level of calcium, elevated ROS level, and increased activities of complexes of respiratory chain. Meanwhile, exposure to CS2 dramatically decreased the mitochondrial transmembrane potential (ΔΨm) and levels of ATP and MPTP opening. Exposure to CS2 can also cause a significantly dose-dependent increase in the expression levels of Bax, Cytc, Caspase-9, and Caspase-3, but decreased the expression level of Bcl-2. Moreover, co-administration of CsA with CS2 can reverse or alleviate the above apoptotic damage effects of CS2 on testicular germ cells. Taken together, our findings suggested that CS2 can cause damage to testicular germ cells via mitochondrial apoptotic pathway, and MPTP play a crucial role in this process.

Exposure to polybrominated diphenyl ethers and female reproductive function: A study in the production area of Shandong, China

Polybrominated diphenyl ethers (PBDEs) are widely used in commercial and household products. Few human studies have examined the effects of PBDE exposure on female reproductive function. We recruited 207 pregnant women when they were admitted for labor from September 2010 to February 2012 as part of a birth cohort study, the Laizhou Wan Birth Cohort study. Maternal sera were analyzed for eight PBDE congeners (BDE-28, -47, -85, -99, -100, -153, -154, and -183) and four sex hormones. BDE-153 exhibited the highest serum level (median 4.67ng/g lipid), followed by BDE-99 (median 3.45ng/g lipid) and BDE-28, -47, and -100 (medians near 2ng/g lipid). BDE-28, -47, -99, -100, and -153 were the most frequently detected (>90%) congeners. Follicle-stimulating hormone (FSH) levels were negatively associated with PBDE exposure. For each natural log unit increase in BDE-47, 100, and ∑5PBDEs, FSH levels changed -1.19IU/L (95% confidence interval [CI]: -1.32, -1.02), -1.17IU/L (95%CI: -1.36, -1.01) and -1.26IU/L (95%CI: -1.55, -1.02) respectively. BDE-85, -153, and -183 were associated with adverse reproductive effects, including an increased risk of threatened abortion (odds ratio [OR] [95% CI]: 1.30 [1.03, 1.62], 1.04 [1.01, 1.08], and 1.03 [1.01, 1.06], respectively). BDE-153 was associated with an increased risk of premature birth (adjusted OR [95% CI]:1.05 [1.01, 1.09]), and BDE-28 was associated with longer time to pregnancy (adjusted OR [95% CI]: 1.34 [1.03, 1.76]). These findings suggest that maternal PBDE exposure may be inversely associated with female reproductive function.

Effects of repeated maternal oral exposure to low levels of trichlorfon on development and cytogenetic toxicity in 3-day mouse embryos.

Trichlorfon is a widely used broad-spectrum agricultural insecticide. Few studies have evaluated the effects of trichlorfon on developing fetuses, especially at early stages of development after low-level maternal exposures. In this study, we evaluated the direct effects of trichlorfon on preimplantation mouse embryos after 30days of maternal exposure (2, 10 and 50mg/kg/day) via drinking water. On gestation day 3 (dg3), blastocysts were collected and evaluated for changes in gross morphology; cell number; the presence of interphase, metaphase, micronuclei (MN) cells and fragmented and pycnotic nuclei. Embryos in the 50mg/kg/day group had a significantly reduced mean cell number per embryo. Furthermore, there was a significant increase in the frequency of pycnotic nuclei and an absence of metaphase cells in the 50mg/kg/day treated group. None of the developmental endpoints evaluated were observed in the 2 and 10mg/kg/day trichlorfon-treated groups. A simultaneous decrease in the cell number and an increase in the frequencies of absent metaphases and pycnotic nuclei indicate that embryonic developmental deficits observed in the 50mg/kg/day exposure group were associated with cytotoxicity.

Carbon disulfide induces mitochondria-mediated apoptosis in Sertoli-germ cells coculture

AbstractCarbon disulfide (CS2), a common organic solvent, induces a variety of adverse effects in the male reproductive system. In this study, we investigated the cytotoxicity, ultrastructural changes, and potential apoptotic induction mechanisms of CS2 in mixed cultures of Sertoli and germ cells. Sertoli and germ cells were cocultured and treated with CS2 for 24 h. Growth rates were noted, and apoptotic cells were identified by Hoechst 33258 staining. Ultrastructure changes were observed via transmission electron microscopy (TEM). Mitochondrial membrane potential and expressions of apoptosis-related factors (cytochrome c, Bax, Bcl-2, caspase-3 and caspase-9) were examined by JC-1 staining, western blot, and real-time PCR. The results showed that CS2 treatment was associated with reduced growth rates of Sertoli-germ cells. Ultrastructure changes in Sertoli-germ cells treated with CS2 were typical of apoptosis. In addition, CS2 treatment depolarized mitochondrial membrane potential, upregulated Bax levels and downregulated Bcl-2 levels, released cytochrome c from the mitochondrial intermembrane space to the cytosol, and triggered mitochondria-mediated apoptosis. Subsequently, caspase-9 and caspase-3 were activated, resulting in Sertoli-germ cells apoptosis. The above data suggest that CS2 has adverse effect on the viability of Sertoli-germ cells and induces apoptosis through mitochondrial pathway.

Association Between Organophosphate Pesticide Exposure and Thyroid Hormones in Pregnant Women

Background: Use of organophosphate pesticides (OPs) is widespread in China. Although animal studies suggested that OP exposure could affect thyroid function, little is explored in human populations. Methods: We investigated levels of OP exposure in pregnant women and the relationship between OPs and thyroid hormones in Shandong, China. We enrolled 637 pregnant women from April 2011 to December 2013. OP exposure was assessed by a questionnaire administered to the pregnant women in the hospital and by analyses of urinary dialkylphosphate (DAP) metabolites of OPs in pregnant women (n = 413). We measured the concentration of five thyroid hormones in serum samples in pregnant women (n = 325) and analyzed the association between DAP metabolites of OPs and thyroid hormones (n = 325). Results: Median levels of DAP metabolites were 9.81 &mgr;g/L for dimethylphosphate (DMP), 0.79 &mgr;g/L for dimethylthiophosphate (DMTP), 5.00 &mgr;g/L for diethylphosphate (DEP), and 0.78 &mgr;g/L for diethylthiophosphate (DETP), which were higher than those reported in developed countries. We found that the total DAP concentration (the sum of DMP, DMTP, DEP, and DETP) in urine was positively associated with free T4 levels (&bgr; = 0.137; 95% confidence interval [CI] = 0.012, 0.263) and negatively associated with thyroid-stimulating hormone levels (&bgr; = −0.145; 95% CI = −0.242, −0.048). Conclusions: The findings suggest that OP exposure may be associated with changes in thyroid function in pregnant women. Given that urinary OP levels in pregnant women in Shandong were much higher than those reported in developed countries, further studies on the effects of OP exposure on thyroid function in pregnant women in China are warranted.

Role of Endoplasmic reticulum apoptotic pathway in testicular Sertoli cells injury induced by Carbon disulfide.

The exposure of Carbon disulfide (CS2) is associated with germ cell injury and male infertility in animals and humans. However, the molecular mechanism is currently unknown. This study show here that CS2-induced Sertoli cells injury via Endoplasmic reticulum (ER) apoptotic pathway. SD male rats were exposed to doses of CS2 (0, 50, 250, 1250mgm(-3)) for 4weeks. After treatment, loose structures of seminiferous tubules and disordered cell arrangements were observed by light microscopy. Ultrastructural lesions, deformed chromatins and vacuoles formed from swollen ER were observed by electron microscopy. After primary culture of Sertoli cells, a dose-dependent increased apoptosis were found. The increased activity of Caspase 3, accumulation of intracellular Ca(2+), up-regulation of mRNA and protein expressions of ER apoptotic relative molecules (Calpain 2, Cleaved-Caspase 12, GRP78 and CHOP) were also found in this study. Altogether, our findings indicated that ER apoptotic pathway played an important role in CS2-induced Sertoli cell impairment.

Genotoxic effects of imidacloprid in human lymphoblastoid TK6 cells

Abstract Among neonicotinoid insecticides, the fastest growing class of insecticides worldwide over the past decade, imidacloprid (IMI) is the most widely used one. The effects of IMI on human health, especially on genetic toxicity have gradually aroused more attention. In this study, a combined in vitro approach employing the thymidine kinase (TK) gene mutation assay, the comet assay and the micronucleus test was taken to assess the genotoxicity of IMI. The mechanism behind IMI was also explored by measuring reactive oxygen species (ROS) in the human lymphoblastoid TK6 cells. The cells were treated with 0.01, 0.1, 1, 5, and 10 μg/mL IMI, and ROS generation was measured by the use of 2,7,-dichlorofluorescin diacetate (DCFH-DA) assay. IMI significantly increased the micronucleus (MN) frequency, TK mutations and DNA damage with a dose-effect relationship, and the lowest effective concentration in those tests was 0.1 μg/mL. However, no obvious change of intracellular ROS was observed for any concentrations. The results indicate that IMI has potential genotoxic effects on TK6 cells, but ROS does not seem to be involved as a mechanism of genotoxicity under the experimental conditions.