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Wide exposure to endocrine-disrupting chemicals (EDCs) poses a great risk on human health. However, few large-scale cohort studies have comprehensively estimated the association between EDCs exposure and mortality risk. This study aimed to investigate the association of urinary EDCs exposure with mortality risk and quantify attributable mortality and economic loss. Multivariable Cox proportional hazards regression models were performed to investigate the association of 38 representative EDCs exposure with mortality risk in the National Health and Nutrition Examination Survey (NHANES). During a median follow-up of 7.7 years, 47,279 individuals were enrolled. All-cause mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, cadmium, antimony, cobalt, and monobenzyl phthalate. Cancer mortality was positively associated with cadmium. Cardiovascular disease (CVD) mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, and 2-hydroxyfluorene. Nonlinear U-shaped relationships were found between all-cause mortality and cadmium and cobalt, which was also identified between 2-hydroxyfluorene and CVD mortality. J-shaped association of cadmium exposure with cancer mortality was also determined. EDCs exposure may cause 56.52% of total deaths (1,528,500 deaths) and around 1,897 billion USD in economic costs. Exposure to certain phthalates, polycyclic aromatic hydrocarbons, phytoestrogens, or toxic metals, even at substantially low levels, is significantly associated with mortality and induces high economic costs.

Triclocarban (TCC), which is used as an antimicrobial agent in personal care products, has been widely detected in aquatic ecosystems. However, the consequence of TCC exposure on embryo development is still elusive. Here, by using zebrafish embryos, we aimed to understand the developmental defects caused by TCC exposure. After exposure to 0.3, 30, and 300 μg/L TCC from 4-hour postfertilization (hpf) to 120 hpf, we observed that TCC exposure significantly increased the mortality and malformation, delayed hatching, and reduced body length. Exposure to TCC also affected the heart rate and expressions of cardiac development-related genes in zebrafish embryos. In addition, TCC exposure altered the expressions of the genes involved in hormonal pathways, indicating its endocrine disrupting effects. In sum, our data highlight the impact of TCC on embryo development and its interference with the hormone system of zebrafish., (© 2019 Wiley Periodicals, Inc.)

Surface water is essential for human health and ecological diversity, but some endocrine disrupting chemicals are detectable. Both thyroid receptor (TR) and androgen receptor (AR) agonistic/antagonistic potencies in grade II surface water in East China were investigated using reporter gene assays. While none of the water exhibited agonistic potency, significant AR and TR antagonistic potencies were detectable. TR antagonistic equivalents (TR-AntEQ) and AR antagonistic equivalents (AR-AntEQ) ranged from 3.6 to 76.1 μg dibutyl phthalate/L and from 2.3 to 242.6 μg flutamide/L, respectively. The TR and AR antagonistic potencies in the Yangtze River watershed were highlighted, with equivalents greater than the lowest observable effect concentration (LOEC) of dibutyl phthalate and flutamide, respectively. Phthalate esters (PAEs) being the most abundant explained most of the TR antagonistic potency, contributing more than 65% of the TR-AntEQ and diisobutyl phthalate (DiBP) was the major contributor. In most surface waters studied, PAEs contributed little of the AR-AntEQ, but the frequently detected octylphenol, nonylphenol and benzo[a]pyrene might be responsible., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Triclosan (TCS) poses potential risks to reproduction and development due to its endocrine-disrupting properties. However, the mechanism of TCS's effects on early embryonic development is little known. Embryonic stem cells (ESC) and zebrafish embryos provide valuable models for testing the toxic effects of environmental chemicals on early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to TCS for 24 h, and general cytotoxicity and the effect of TCS on pluripotency were then evaluated. In addition, zebrafish embryos were exposed to TCS from 2- to 24-h post-fertilization (hpf), and their morphology was evaluated. In mESC, alkaline phosphatase staining was significantly decreased after treatment with the highest concentration of TCS (50 μM). Although the expression levels of Sox2 mRNA were not changed, the mRNA levels of Oct4 and Nanog in TCS-treated groups were significantly decreased compared to controls. In addition, the protein levels of Oct4, Sox2 and Nanog were significantly reduced in response to TCS treatment. MicroRNA (miR)-134, an expression inhibitor of pluripotency markers, was significantly increased in TCS-treated mESC. In zebrafish experiments, after 24 hpf of treatment, the controls had developed to the late stage of somitogenesis, while embryos exposed to 300 μg/L of TCS were still at the early stage of somitogenesis, and three genes (Oct4, Sox2 and Nanog) were upregulated in treated groups when compared with the controls. The two models demonstrated that TCS may affect early embryonic development by disturbing the expression of the pluripotency markers (Oct4, Sox2 and Nanog).

Bisphenol A (BPA) poses potential risks to reproduction and development. However, the mechanism of BPA's effects on early embryonic development is still unknown. Embryonic stem cells (ESC) and embryoid bodies (EB) provide valuable in vitro models for testing the toxic effects of environmental chemicals in early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to BPA for 24h, and general cytotoxicity and the effect of BPA on pluripotency were then evaluated. Meanwhile, mouse embryoid bodies (mEB) were exposed to BPA up to 6 days and their differentiation capacity was evaluated. In mESC and mEB, we found that BPA up-regulated pluripotency markers (Oct4, Sox2 and Nanog) at mRNA and/or protein levels. Moreover, BPA increased the mRNA levels of endodermal markers (Gata4,Sox17) and mesodermal markers (Sma,Desmin), and reduced the mRNA levels of ectodermal markers (Nestin,Fgf5) in mEB. Furthermore, microRNA(miR)-134, an expression inhibitor of pluripotency markers including Oct4, Sox2 and Nanog, was decreased both in BPA-treated mESC and mEB. These results firstly indicate that BPA may disturb pluripotency in mESC and differentiation of mEB, and may inhibit ectodermal lineage differentiation of mEB while miR-134 may play a key role underlying this effect., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Second-grade surface water and ground water are considered as the commonly used cleanest water in the Yangtze River Delta, which supplies centralized drinking water and contains rare species. However, some synthetic chemicals with estrogenic disrupting activities are detectable. Estrogenic activities in the second-grade surface water and ground water were surveyed by a green monkey kidney fibroblast (CV-1) cell line based ER reporter gene assay. Qualitative and quantitative analysis were further conducted to identify the responsible compounds. Estrogen receptor (ER) agonist activities were present in 7 out of 16 surface water and all the ground water samples. Huaihe River and Yangtze River posed the highest toxicity potential. The highest equivalent (2.2 ng E2/L) is higher than the predicted no-effect-concentration (PNEC). Bisphenol A (BPA) contributes to greater than 50% of the total derived equivalents in surface water, and the risk potential in this region deserves more attention and further research., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Perfluorooctanoic acid (PFOA), a persistent perfluorinated compound, is distributed widely in wildlife and humans. Recent studies showed that PFOA is a suspected endocrine disruptor. But the results are somewhat contradictory and the mechanisms are unclear. In this study, we investigated the endocrine-related effects of PFOA using a series of assays. The lower dose effect of PFOA on development and endocrine-related gene expression were assessed in a short-term zebrafish assay in vivo. To clarify the mechanism of PFOA, in vitro assays were performed. We tested the hormone receptor activities of ER, AR, and TR against PFOA using reporter gene assays. The hormone levels of estradiol (E2) and testosterone (T), the expression of major steroidogenic genes and the key steroidogenic gene regulator steroidogenic factors 1 (SF-1) were measured after PFOA exposure in H295R steroidogenesis assay. Exposure of zebrafish embryo to PFOA resulted in higher expression of esr1, hhex and pax. PFOA is able to interfere with hormone receptor ER and TR. In H295R cells, PFOA could increase the E2 production and decrease the T production, altered the expression of major steroidogenic genes and regulator SF-1. The current findings indicated the potential endocrine-related effects of PFOA and provided novel information for human risk assessment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo., (Copyright © 2012 SETAC.)

The thyroid hormone disrupting activities of drinking water sources from the lower reaches of Yangtze River were examined using a reporter gene assay based on African green monkey kidney fibroblast (CV-1) cells. None of the eleven tested samples showed thyroid receptor (TR) agonist activity. Nine water samples exhibited TR antagonist activities with the equivalents referring to Di-n-butyl phthalate (DNBP) (TR antagonist activity equivalents, ATR-EQ(50)s) ranging from 6.92 × 10(1) to 2.85 × 10(2) μg DNBP/L. The ATR-EQ(50)s and TR antagonist equivalent ranges (ATR-EQ(30-80) ranges) for TR antagonist activities indicated that the water sample from site WX-8 posed the greatest health risks. The ATR-EQ(80)s of the water samples ranging from 1.56 × 10(3) to 6.14 × 10(3) μg DNBP/L were higher than the NOEC of DNBP. The results from instrumental analysis showed that DNBP might be responsible for the TR antagonist activities in these water samples. Water sources along Yangtze River had thyroid hormone disrupting potential., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Octylphenol (OP) and Trichlorophenol (TCP) act as endocrine disruptors and have effects on male reproductive function. We studied the interactions between 4-tert-Octylphenol (4-t-OP), 4-n- Octylphenol (4-n-OP), 2,3,4-Trichlorophenol (2,3,4-TCP), 2,4,5-Trichlorophenol (2,4,5-TCP) urinary exposure levels and polymorphisms in selected xenobiotic metabolism enzyme genes among 589 idiopathic male infertile patients and 396 controls in a Han-Chinese population. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to measure alkylphenols and chlorophenols in urine. Polymorphisms were genotyped using the SNPstream platform and the Taqman method. Among four phenols that were detected, we found that only exposure to 4-t-OP increased the risk of male infertility (P(trend) = 1.70×10(-7)). The strongest interaction was between 4-t-OP and rs4918758 in CYP2C9 (P(inter) = 6.05×10(-7)). It presented a significant monotonic increase in risk estimates for male infertility with increasing 4-t-OP exposure levels among men with TC/CC genotype (low level compared with non-exposed, odds ratio (OR) = 2.26, 95% confidence intervals (CI) = 1.06, 4.83; high level compared with non-exposed, OR = 9.22, 95% CI = 2.78, 30.59), but no associations observed among men with TT genotype. We also found interactions between 4-t-OP and rs4986894 in CYP2C19, and between rs1048943 in CYP1A1, on male infertile risk (P(inter) = 8.09×10(-7), P(inter) = 3.73×10(-4), respectively).We observed notable interactions between 4-t-OP exposure and metabolism enzyme gene polymorphisms on idiopathic infertility in Han-Chinese men.

Thyroid hormone is essential for the development of humans. However, some synthetic chemicals with thyroid disrupting potentials are detectable in drinking water. This study investigated the presence of thyroid active chemicals and their toxicity potential in drinking water from five cities in eastern China by use of an in vitro CV-1 cell-based reporter gene assay. Waters were examined from several phases of drinking water processing, including source water, finished water from waterworks, tap water, and boiled tap water. To identify the responsible compounds, concentrations and toxic equivalents of a list of phthalate esters were quantitatively determined. None of the extracts exhibited thyroid receptor (TR) agonist activity. Most of the water samples exhibited TR antagonistic activities. None of the boiled water displayed the TR antagonistic activity. Dibutyl phthalate accounted for 84.0-98.1% of the antagonist equivalents in water sources, while diisobutyl phthalate, di-n-octyl phthalate and di-2-ethylhexyl phthalate also contributed. Approximately 90% of phthalate esters and TR antagonistic activities were removable by waterworks treatment processes, including filtration, coagulation, aerobic biodegradation, chlorination, and ozonation. Boiling water effectively removed phthalate esters from tap water. Thus, this process was recommended to local residents to reduce certain potential thyroid related risks through drinking water.

Methoxylated brominated diphenyl ethers (MeO-BDEs) in aquatic environments have been found to be primarily of natural origin in the marine environment and not from biotransformation of synthetic PBDEs. Two of the eight MeO-PBDEs (2'-MeO-BDE-68 and 6-MeO-BDE-47) that were detected in anchovy from the Yangtze River Delta, were natural products from marine organisms. So 2'-MeO-BDE-68 and 6-MeO-BDE-47 were chosen to study the potential to modulate androgen, estrogen, or thyroid hormone receptor- (AR, ER, ThR) mediated responses by use of reporter gene assays. 2'-MeO-BDE-68 was antiandrogenic at 50 μM, estrogenic at 10 μM and antiestrogenic at 10 and 50 μM (IC50=4.88 μM). 2'-MeO-BDE-68 enhanced luciferase expression by 5 nM T3 at 50 μM. 6-MeO-BDE-47 exhibited potent antiandrogenicity at 1 μM and greater (IC50=41.8 μM) and possessed estrogenic activity at 10 μM and antiestrogenic activity at 10 and 50 μM (IC50=6.02 μM)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Polybrominated diphenyl ethers (PBDEs) constitute an important group of flame retardants. 2,2',4,4',6-Pentabromodiphenylether (BDE100) is a prominent PBDE congener in some human populations. The potential of BDE100 to modulate responses mediated by the estrogen (ER), thyroid hormone (ThR) or androgen receptors (AR) were investigated by use of transactivation reporter gene assays. The African green monkey kidney CV-1 cell transiently transfected with the constructed reporter gene plasmid ERE-TATA-Luc and pUAS-tk-Luc with luciferase (Luc) under control of the estrogen response (ERE), or thyroid hormone response (ThRE) elements were used to evaluate (anti)estrogen and thyroid effects of BDE100. The (anti)androgenic potency of BDE100 was also evaluated by use of MDA-kb2 cells, which were stably transfected with MMTV-luciferase. The assays displayed appropriate responses to known natural estrogen 17β-estradiol (E2), ThR ligand triiodothyronine (T3), and the AR agonist 5α-dihydrotestosterone (DHT). 10 or 50 μM BDE100 significantly up-regulated expression of Luc under control of the ER. Antiestrogenic potency was observed for BDE100 (IC50 = 6.21 μM). Co-exposure to 50 μM BDE100 significantly enhanced expression of Luc caused by 5 nM T3. BDE100 was antiandrogenic at 10 and 50 μM with an IC50 of 28.60 μM BDE100. These results suggest that BDE100 can modulate the endocrine system in multiple ways by interfering with several hormonal signaling pathways simultaneously.

Thyroid hormone (TH) agonist and antagonist activities of water sources along the Yangtze River in China were surveyed by a green monkey kidney fibroblast (CV-1) cell-based TH reporter gene assay. Instrumental analysis was conducted to identify the responsible thyroid-active compounds. Instrumentally derived l-3,5,3'-triiodothyronine (T(3)) equivalents (T(3)-EQs) and thyroid receptor (TR) antagonist activity equivalents referring to dibutyl phthalate (DBP-EQs) were calculated from the concentrations of individual congeners. The reporter gene assay demonstrated that three out of eleven water sources contained TR agonist activity equivalents (TR-EQs), ranging from 286 to 293 ng T(3)/L. Anti-thyroid hormone activities were found in all water sources with the TR antagonist activity equivalents referring to DBP (Ant-TR-EQs), ranging from 51.5 to 555.3 μg/L. Comparisons of the equivalents from instrumental and biological assays suggested that high concentrations of DBP and di-2-ethylhexyl phthalate (DEHP) were responsible for the observed TR antagonist activities at some locations along the Yangtze River., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The potential of 2,2',4,4'-tetrabromodiphenyl ether (BDE47) and its related hydroxylated analogs (2'-HO-BDE28, 6-HO-BDE47, 4'-HO-BDE17, and 4'-HO-BDE49) to modulate estrogen/thyroid/androgen receptor-(ER, TR, AR), mediated responses were investigated by use of reporter gene assays. Exposure to 1 or 10 μM, 4'-HO-BDE17 significantly up-regulated expression of Luc, whereas other four chemicals did not induce Luc expression under control of the ER. Anti-estrogenic potency was observed for 4'-HO-BDE17 (IC50=1.14 μM)>6-HO-BDE47 (IC50=2.65 μM)>2'-HO-BDE28 (IC50=9.49 μM)>BDE47 (IC50=21.11 μM). No anti-estrogenic effect of 4'-HO-BDE49 was observed. Both 4'-HO-BDE17, 4'-HO-BDE49 resulted in greater responses of Luc expression induced by T3. BDE47, 2'-HO-BDE28, 6-HO-BDE47 did not show any effect on the expression of Luc induced by 5 nM T3. 6-HO-BDE47 (IC50=0.34 μM)>4'-HO-BDE17 (IC50=1.41 μM)>BDE47 (IC50=3.83 μM)>2'-HO-BDE28 (IC50=29.22 μM) exhibited anti-androgenic potency, while 4'-HO-BDE49 did not show androgenic transcriptional activity., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Pyrethroid insecticides, the most commonly used insecticides worldwide, are suspected endocrine-disrupting chemicals. But their interactions with hormone receptors are still unclear. The present study intended to evaluate and compare the hormone receptor (estrogen receptor [ER], androgen receptor [AR], and thyroid hormone receptor [TR]) activities of nine pyrethroids (cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, etofenprox, fenvalerate, permethrin, and tetramethrin) and their metabolites (3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropne carboxylic acid [DCCA] and 3-phenoxybenzoic acid [3-PBA]) using receptor-mediated luciferase reporter gene assays. Of the 11 compounds tested, four showed very weak ER agonistic activities and six displayed antiestrogenic effects, among which cyhalothrin and DCCA possessed the most potent estrogenic and antiestrogenic activity respectively. Antagonistic effects to AR were found in 7 compounds, with cyfluthrin and deltamethrin exhibiting stronger AR antagonistic capacity. In the TR assay, all of tested chemicals except DCCA showed antagonistic effects. In this study, we provided evidence that a variety of pyrethroids and their metabolites might disrupt the function of multiple nuclear hormone receptors and thus have the potentials to affect the endocrine and the reproductive systems in humans.

Phthalates are widely used in the plastic industry and food packaging, imparting softness and flexibility to normally rigid plastic medical devices and children's toys. Even though phthalates display low general toxicity, there is increasing concern on the effects of endocrine system induced by some of phthalate compounds. The hormone activity of dibutyl phthalate (DBP), mono-n-butyl phthalate (MBP) and di-2-ethylhexyl phthalate (DEHP) were assessed using the luciferase reporter gene assays. The results showed that DBP, MBP and DEHP, not only exhibited potent antiandrogenic activity, with IC(50) value of 1.05x10(-6), 1.22x10(-7)M and exceeding 1x10(-4)M respectively, but also showed the androgenic activity with EC(50) value of 6.17x10(-6), 1.13x10(-5)M and exceeding 1x10(-4)M. We also found that all the three related chemicals possessed thyroid receptor (TR) antagonist activity with IC(50) of 1.31x10(-5), 2.77x10(-6)M and exceeding 1x10(-4)M respectively, and none showed TR agonist activity. These results indicate that TR might be the targets of industrial chemicals. In the ER mediate reporter gene assay, three chemicals showed no agonistic activity except for DBP, which appeared weakly estrogenic at the concentration of 1.0x10(-4)M. Together, the findings demonstrate that the three phthalates could simultaneously disrupt the function of two or more hormonal receptors. Therefore, these phthalates should be considered in risk assessments for human health.

The endocrine-disrupting equivalents in effluents from three chemical industry wastewater treatment systems in the vicinity of Yangtze River were determined by several transactivation reporter gene assays. Transient transfections of African green monkey kidney cell line (CV-1) were used to determine the estrogenic, anti-androgenic and anti-thyroid equivalents in the effluents. Organic extracts of the effluents contained compounds that were potent anti-androgens and the activities measured as an equivalent concentration of flutamide were 45.53, 34.65 and 91.61 nM, respectively. The extracts also contained detectable concentrations of thyroid antagonists. Estrogenic activities, measured with the reporter gene assay, were near or below the method detection limit (0.58 pM as E2). Concentrations of some of the major constituents such as di(2-ethylhexyl)phthalate, dibutyl phthalate, 2,6-dinitrotoluene and nitrobenzene were quantified. The data suggest that the reporter gene assay is useful to predication of endocrine disrupting effects in polluted aquatic body.

Highlights: [•] Pyrethroids possess weaker estrogenic activity. [•] The metabolite of pyrethroid possessed antiestrogenic activity. [•] Pyrethroid showed similar response on the function of rat and human estrogen receptors in vitro assay. [ABSTRACT FROM AUTHOR]

Abstract: Widespread human exposure to phenols has been documented recently, and some phenols which are potential endocrine disruptors have demonstrated adverse effects on male reproduction in animal and in vitro studies. However, implications about exposure to phenols and male infertility are scarce in humans. Case–control study of 877 idiopathic infertile men and 713 fertile controls was conducted. Urinary levels of bisphenol A, benzophenone-3, pentachlorophenol, triclosan, 4-tert-octylphenol (4-t-OP), 4-n-octylphenol (4-n-OP) and 4-n-nonylphenol (4-n-NP) and semen parameters were measured. After multivariate adjustment, we found 4-t-OP, 4-n-OP and 4-n-NP exposure was associated with idiopathic male infertility (p-value for trend: <0.0001, 0.014 and 0.001, respectively). Aside from these associations, 4-t-OP and 4-n-NP exposure was also associated with idiopathic male infertility with abnormal semen parameters. Moreover, we observed significant associations between sum alkylphenols (APs) exposure and idiopathic male infertility. There were no relationships between exposure to other phenols and idiopathic male infertility in the present study. Our study provides the first evidence that exposure to APs (4-t-OP, 4-n-OP and 4-n-NP) is associated with idiopathic male infertility. [Copyright &y& Elsevier]

Abstract: Objectives: Epoxide hydrolases are involved in detoxifying and excreting the environmental chemicals, which are associated with decreased semen quality and male infertility. We hypothesized that polymorphisms in epoxide hydrolases may be associated with risk of oligozoospermia and asthenospermia. Design and methods: In this study, 468 fertile controls and 672 idiopathic male infertile patients were recruited. SNPstream and TaqMan assay were used to genotype four single nucleotide polymorphisms in EPHX1 and EPHX2. The semen analysis was performed by computer-assisted semen analysis system. Results: Our results demonstrated that rs1042064 of EPHX2 was significantly associated with decreased risk of oligozoospermia (OR=0.65, 95% CI: 0.44–0.98) and asthenospermia (OR=0.66, 95% CI: 0.46–0.94). Conclusions: Our results provided evidence that genetic variants in epoxide hydrolases may modify the risk of oligozoospermia and asthenospermia in Han-Chinese population. [Copyright &y& Elsevier]

Abstract: Background: It is acknowledged that Cytochrome P450 1B1 (CYP1B1) plays a crucial role in metabolism and is involved in lots of diseases. We carried out this study to evaluate the association between CYP1B1 single nucleotide polymorphisms (SNPs) and male infertility in the Han-Chinese population with abnormal semen parameters. Methods: We genotyped five CYP1B1 polymorphisms by using TaqMan allelic discrimination assay and Genome Lab SNP-stream. A total of 591 idiopathic infertile men and 419 fertile controls were comprised in the research. Semen quality analysis was performed using computer assisted sperm analysis. According to semen parameters, we divided cases into 3 subgroups in the stratified analysis. Results: In our study, we only found genetic variant rs1056836 is correlated with idiopathic male infertility (P =0.012). Additionally, in strategy analysis, rs1056836 may decrease the risk of abnormal sperm motility (OR=0.11, 95% CI=0.01, 0.86). While other four variants showed no significant association with male infertility. Conclusions: Our results suggested that polymorphism of CYP1B1 modified the risk of male infertility, and men harboring this polymorphism had lower risk of abnormal sperm parameters. These findings should be validated by more epidemiological and functional studies. [Copyright &y& Elsevier]

Many pesticides possess hormonal activities and have been classified as endocrine disrupting chemicals. Synthetic pyrethroids are one kind of the most common pesticides used in the world. In the present study, we explored the association between serum reproductive hormone levels and urinary creatine (CR) adjusted concentration of 3-phenoxybenzoic acid (3-PBA), a general metabolite of pyrethroids, in Chinese adult men. The study subjects (n =212) were from the affiliated hospitals of Nanjing Medical University. By using GC–MS, urinary 3-PBA level of each subject was measured and adjusted by urinary CR. Blood samples were collected for measuring the serum levels of reproductive hormones, including follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T) and prolactin (PRL). All the subjects had detectable levels of 3-PBA in their urine samples. The median concentration of 3-PBA was 0.815μgg −1of CR. The results showed that there was positive associations between the levels of serum LH and 3-PBA (p =0.013) but negative associations between E2 and 3-PBA level (p =0.022), and the adjusting p-value was 0.044 for LH and E2, which suggested that pyrethroids are capable of disrupting the male endocrine function. In adult men, urinary 3-PBA levels were associated with increased LH and reduced E2 levels. On a population level, these reductions show potential public health importance because of widespread exposure to these pesticides. [Copyright &y& Elsevier]