[The involvement and underlying mechanism of the aryl hydrocarbon receptor (AhR) in the impairment of male mammalian fertility induced by environmental pollutants].

In recent decades, there has been a consistent decline in semen quality across the globe, with environmental pollution emerging as the predominant factor. Persistent organic pollutants (POPs) have garnered considerable attention due to their potent biological toxicity and resistance to natural degradation. Within this class of pollutants, polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) have been identified as detrimental agents that can disrupt cellular physiological functions by activating aryl hydrocarbon receptor (AhR). However, the precise role of AhR in the adverse effects of environmental pollutants on male mammalian fertility remains incompletely understood. This article provides a comprehensive review of the impact of various environmental pollutants, specifically PAHs such as benzo[a]pyrene, 3-methylcholanthrene, and 7,12-dimethylbenzo[a]anthracene, HAHs including 2,3,7,8-tetrachlorodibenzo-p-dioxins, polychlorinated biphenyls, polybrominated diphenyl ethers, and the pollutant complex PM2.5, as well as cigarette smoke condensates, on male mammalian reproductive function. Additionally, this review focuses on the role of the AhR in mediating these effects. The objective of this review is to elucidate the involvement of AhR in the regulation of male mammalian fertility, thereby offering insights for prospective investigations into the interplay between AhR and male reproductive function, as well as the etiology of idiopathic male infertility in clinic.

Immunity and inflammatory responses in gilthead sea bream (Sparus aurata L.) exposed to sub-lethal mixture of carbamazepine, cadmium chloride and polybrominated diphenyl ether.

Chemical contaminants such as industrial and urban by-products, pharmaceuticals, drugs metabolites and, plastics, are continuously found in the oceans, affecting its quality and organism's welfare. Although these compounds are found at concentrations ranged ng L-1, there is an increasing concern about the potential adverse effects of the interactions among those substances present, simultaneously, in a mixture. In the present study, specimens of sea bream (Sparus aurata) were exposed, by food, to rising concentrations of a mixture of carbamazepine, polybrominated diphenyl ether-47 and cadmium chloride, for 15 days and then, maintained, with the same control diet, without contaminants, for other 15 days. Samples of skin mucus, serum, head-kidney, liver and intestine were sampled at 0, 15 and 30 days. Cellular immune parameters were evaluated on head-kidney, as well as humoral parameters were determined on skin mucus and serum. In addition, the expression of some genes, related to immunity, was analysed on liver and intestine. Both cellular and humoral response were affected at 15 days, showing slightly signs of recovery at 30 days. Besides, the expression of immune-related genes was highly affected, suggesting the development of inflammatory processes, as well as a reduction of immune parameters. Overall, the mixture of compounds severally affected the immune system of sea bream, suggesting a lower degree of recovery. The prolonged exposure to a mixture of these compounds could entail serious change on population immunity and, eventually, promote changes on marine biota.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth.

OBJECTIVES: Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. METHODS: Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. RESULTS: We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. CONCLUSIONS: These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

Associations between prenatal maternal exposure to per- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) and birth outcomes among pregnant women in San Francisco.

BACKGROUND: Perfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are used in consumer products for their water repellent and flame retardant properties, respectively. However, there is widespread prenatal exposure and concern about their potential harm to the developing fetus. Here, we utilized data from a demographically diverse cohort of women in San Francisco, CA to examine associations between prenatal exposure to PFAS and PBDEs with gestational age and birth weight for gestational age z-scores. METHODS: Women included in this analysis were enrolled in the Chemicals in our Bodies (CIOB) cohort study (N = 506). PFAS and PBDEs were measured in serum obtained during the second trimester of pregnancy. Linear regression models were used to calculate crude and adjusted ß coefficients for the association between PFAS and PBDE concentrations in tertiles and gestational age and birth weight z-scores. Individual PFAS and PBDE concentrations, as well as their sums, were examined in separate models. RESULTS: The highest compared to lowest tertile of BDE-47 was associated with shorter gestational age (ß = - 0.49, 95% confidence interval [CI] = - 0.95, - 0.02). Additionally, exposure to BDE-47 and BDE-99 in the middle tertile was also associated with a reduction in birth weight z-scores (ß = - 0.26, 95% CI = -0.48, - 0.04; ß = - 0.25, 95% CI = -0.47, - 0.04, respectively) compared to those in the lowest tertile of exposure. No consistent associations were observed between increasing PFAS concentrations and gestational age or birth weight z-scores. DISCUSSION: Among a diverse group of pregnant women in the San Francisco Bay Area, we found non-linear associations between prenatal exposure to PBDEs during the second trimester of pregnancy and birth weight z-scores. However, most PFAS congeners were not associated with adverse birth outcomes. PFAS and PBDE concentrations were lower in our cohort relative to other studies. Future research should assess the effects of emerging and persistent PFAS and PBDEs on birth outcomes, as some congeners are being phased out and replaced by chemically similar structures.

Association of polybrominated diphenyl ether (PBDE) levels with biomarkers of placental development and disease during mid-gestation.

BACKGROUND: Polybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. A hypothesized mechanism is via alterations in placental development and function. However, we lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function. METHODS: To evaluate the relationship between PBDE levels and placental biomarkers during mid-gestation of human pregnancy (n = 62), we immunolocalized three molecules that play key roles in cytotrophoblast (CTB) differentiation and interstitial/endovascular uterine invasion-integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and metalloproteinase-1 (MMP1)-and assessed three morphological parameters as potential indicators of pathological alterations using H&E-stained tissues-leukocyte infiltration, fibrinoid deposition, and CTB endovascular invasion. We evaluated associations between placental PBDE levels and of biomarkers of placental development and disease using censored Kendall's tau correlation and linear regression methods. RESULTS: PBDEs were detected in all placental samples. We observed substantial variation in antigen expression and morphological endpoints across placental regions. We observed an association between PBDE concentrations and immunoreactivity of endovascular CTB staining with anti-ITGA1 (inverse) or interstitial CTBs staining with anti-CDH5 (positive). CONCLUSIONS: We found several molecular markers that may be sensitive placental indicators of PBDE exposure. Further, this indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stage-specific antigens.

Exposure to Persistent Organic Pollutants and Birth Characteristics: The Upstate KIDS Study.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may be associated with obesogenic effects in offspring. Our study is the first to investigate associations between concentrations of POPs from newborn dried blood spots (DBS) and birth characteristics. METHODS: Concentrations of 10 polychlorinated biphenyl congeners (PCBs), polybrominated diphenyl ether-47 (PBDE-47), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were measured from DBSs collected at birth from 2,065 singleton infants. DBS samples were pooled in groups of five and assayed together to reach limits of detection. Differences in risk of large for gestational age (LGA, defined as >90th percentile of birth weight for sex and gestational age), small for gestational age (SGA, <10th), and preterm birth (gestational age <37 weeks) were estimated using logistic regression per unit (ng/ml) increase in concentration of each chemical, adjusting for individual-level covariates, including maternal age, race/ethnicity, prepregnancy BMI, education, parity, smoking, and infant sex while assuming a gamma distribution and using multiple imputation to account for pools. RESULTS: There were 215 (11.3%) singletons born LGA, 158 (7.5%) born SGA, and 157 (7.6%) born preterm. Higher concentrations of POPs were positively associated with slightly higher risk of LGA and higher birth weight. CONCLUSIONS: Relationships between POPs measured in newborn DBS and birth size were mixed. Pooled analysis methods using DBS could address challenges in limits of detection and costs for population-based research.

Alteration of Placental Deiodinase 3 Expression by BDE 209 and Possible Protection by Taurine in Human Placenta-Derived JEG Cells Under Hypoxia.

Thyroid hormones are key hormones involved in growth and development. Changes in their levels can cause embryonic brain developmental damage in the first trimester. Studies have shown that polybrominated diphenyl ethers (PBDEs) have developmental neurotoxicity as environmental pollutants, and exposure during pregnancy can cause irreversible brain damage in offspring, similar to the interference effects of thyroid hormones, but its mechanism has not yet been understood. Since the physiological environment for placental cells is highly hypoxic, in the current study, the human placenta-derived JEG cells were cultured at 1% oxygen, 4% carbon dioxide and 94% nitrogen, to reflect in vivo scenario, and the possible protection of taurine on BDE 209-mediated toxicity in JEG cells was studied. Our data showed that different concentrations of BDE 209 can have profound effects on cell viability and placental deiodinase 3 expression under hypoxic culture condition. Taurine was found to improve BDE 209-induced reductions in cell viability and altered gene and protein expressions of placental deiodinases. The results provide a reference for the establishment of early biomarkers and effective preventive measures.

Effect of Taurine on Alterations in Deiodinase 3 Expression Induced by BDE 209 in Human Neuroblasoma-Derived SK-N-AS Cells.

PBDEs (stands for polybrominated diphenyl ethers) are extensively utilized flame retardants, and BDE 209 is one of the most widely used congeners. Studies have suggested the general toxic effects of PBDEs on the endocrine system and neural development. Our previous studies found that BDE 209 changed Type 3 iodothyronine deiodinase (Dio 3) expression in human SK-N-AS neuroblastoma cells. The current study was designed to examine the potential protection of taurine on alterations of Dio 3 expression induced by BDE 209 in SK-N-AS cells. Briefly, SK-N-AS cells were pretreated with taurine prior to the BDE 209 treatment, and the cell viability was evaluated by the MTT (methyl-thiazolyl-tetrazolium) assay. The disturbance or restoration in the levels of Dio 3 proteins and mRNA were observed separately by the western blot and qRT-PCR. Our data showed that taurine moderately attenuated BDE 209-mediated the loss of cell viability. Also, taurine moderately prevented the reduction in the Dio 3 protein expression and mRNA expression induced by BDE 209 in the SK-N-AS cells. Our findings indicated that taurine potentially provide the protection on PBDEs-induced toxicity on endocrine and neuro-development.

The Protection of Taurine on Abnormal Expression of Deiodinase 3 Induced by BDE 209 in JEG Cells Under the Normal Culture Conditions.

Taurine is an important amino acid for the growth and development of the central nervous system and plays an important role in the development of the nervous system. Many studies have shown that taurine can prevent and repair neurodevelopmental damage, and its mechanism has also become a research hotspot. While most studies focus on nerve cells, less on placental cells that are closely related to early neurodevelopment (developmental neurotoxicity) by modulating fetal circulation level of thyroid hormones. Studies have shown that exposure of placental cells to the common environmental endocrine disruptor BDE 209 during early pregnancy may lead to developmental neurotoxicity due to thyroid hormone interference caused by abnormal expression of deiodinases. Therefore, in this study, the placenta-derived JEG cells cultured at 95% air/5% CO2 was used as a in vitro model, and the potential protection from taurine on BDE 209-mediated cytotoxicity was examined. When BDE 209 was found to cause a decrease in cell viability and disturbance in the gene and protein expressions of placental deiodinase 3, pretreatment of the JEG cells with taurine can moderately reduce the BDE 209-meditated cytotoxicity, and restore gene and protein expressions of placental deiodinase, so that thyroid hormone levels tend to be normal in cell culture medium. Our data suggest that taurine may have some protection on the developmental neurotoxicity caused by BDE 209.

Maternal and paternal serum concentrations of persistent organic pollutants and the secondary sex ratio: A population-based preconception cohort study.

Recent declines in the secondary sex ratio (SSR), defined as the ratio of males to females at birth, in some industrialized countries may be attributed to exposure to environmental toxicants such as persistent organic pollutants (POPs). This study aimed to evaluate the association of couples' preconception exposure to POPs with the SSR. The study cohort comprised 235 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and prospectively followed through delivery of a singleton birth. Upon enrollment, couples' serum concentrations (ng/g) were measured for 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, and 36 polychlorinated biphenyls (PCBs). Birth outcome data including infant sex were collected upon delivery. Modified Poisson regression models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of a male birth for each chemical. Of the 56 POPs examined, maternal PCB 128 and paternal hexachlorobenzene were significantly associated with a female excess (RRs, 0.75 [95% CI, 0.60-0.94] and 0.81 [95% CI, 0.68-0.97] per 1SD increase in log-transformed serum chemical concentrations, respectively), whereas maternal mirex and paternal PCB 128 and p,p'-dichlorodiphenyldichloroethylene were significantly associated with a male excess (RR range, 1.10-1.22 per 1SD increase in log-transformed serum chemical concentrations). After adjusting for multiple comparisons, only maternal mirex remained significantly associated with the SSR. This exploratory study on multiple classes of POPs demonstrated no conclusive evidence on the association between parental preconception exposure to POPs and the SSR.

Ingested microplastic as a two-way transporter for PBDEs in Talitrus saltator.

The presence and accumulation of plastic waste into the marine environment are well known environmental issues. Microplastics (MPs) end up in sea waters and, due to their hydrophobicity and high surface/volume ratio, POPs tend to sorb and accumulate to their surface. The supralittoral amphipod Talitrus saltator (T. saltator) was selected to study the role of MPs in the transfer of organic pollutants and to investigate if ingested MPs could either transfer contaminants to biota or clean it adsorbing pollutants taken from the diet. T. saltator is an established POPs (Persistent Organic Pollutants) biomonitor in coastal environments and it is able to swallow microplastics in natural condition. Two laboratory experiments were performed and T. saltator was exposed to a labelled polybrominated diphenyl ether (13C-labelled BDE-47) to investigate the opposite gradient role of MPs. X Ray Micro-CT (Micro-Computed Tomography) analyses were also performed on sandhopper samples to evaluate the uptake of MPs via digestive tract. The results showed that MPs ingestion could whether transfer and remove contaminants from T. saltator, indicating a partial balance among positive and negative effects. This study has underlined MP potential double role demonstrating that MP can act both as a carrier and scavenger for the bioaccumulation of organic pollutants (i.e. PBDEs), suggesting that chemicals leaching from MPs could have a limited impact to biota.

Effects of halogenated contaminants on reproductive development in wild mink (Neovison vison) from locations in Canada.

The concept of the Anthropocene, that humans are now re-engineering global ecosystems, is in part evidenced by the pervasive pollution by persistent organic pollutants (POPs). Certain POPs are hormone mimics and can disrupt endocrine and hence reproductive processes, shown mainly by laboratory studies with model species. There are, in contrast, fewer confirmations of such disruption from eco-epidemiological studies of wild mammals. Here we used the American mink (Neovison vison) as a sentinel species for such a study. Over the period 1998-2006, 161 mink carcasses were obtained from commercial trappers in the Canadian provinces of British Columbia and Ontario. Mink were aged, sexed, measured, and body condition assessed. Livers were analyzed either individually or pooled for organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), and subsets for polybrominated diphenyl ethers (PBDEs). We primarily addressed whether contaminants affected male reproductive development by measuring baculum size and assessing the influences of age and body condition. We also considered the influence of spatial variation on relative exposure and size of baculum. Statistical models separated by age class revealed that significant relationships between baculum length or mass and juvenile mink were mostly positive, whereas for adults and first year mink they were mostly negative. A significant negative relationship for adult mink was determined between DDE and both baculum length and mass. For juvenile mink we found significant positive relationships between ∑PCBs, DDE and ∑PBDEs with baculum length. Our results provide some indication of negative effects of halogenated contaminants on male reproductive development in wild mink, and the most likely candidate chemical is the confirmed anti-androgenic compound, DDE, rather than PCBs or other compounds.

Infection by Nanophyetus salmincola and Toxic Contaminant Exposure in Out-migrating Steelhead from Puget Sound, Washington: Implications for Early Marine Survival.

Out-migrating steelhead Oncorhynchus mykiss from four Puget Sound rivers and associated marine basins of Puget Sound in Washington State were examined for the parasite, Nanophyetus salmincola in 2014 to determine whether recent trends in reduced marine survival are associated with the presence of this pathogen. A subset of steelhead from three of these river-marine basin combinations was analyzed for the presence of persistent organic pollutants (POPs) to assess whether exposure to these contaminants is a contributing factor to their reduced marine survival. The prevalence and parasite load of N. salmincola were significantly higher in fish from central and southern Puget Sound than in fish from river systems in northern Puget Sound. The proportion of steelhead samples with concentrations of POPs higher than adverse effects thresholds (AETs) or concentrations known to cause adverse effects was also greater in fish from the central and southern regions of Puget Sound than in those from the northern region. Polybrominated diphenyl ether concentrations associated with increased disease susceptibility were observed in 10% and 40% of the steelhead sampled from central and southern Puget Sound regions, respectively, but in none of the fish sampled from the northern region. The AET for polychlorinated biphenyls was exceeded in steelhead collected from marine habitats: 25% of the samples from the marine basins in the central and southern regions of Puget Sound and 17% of samples from northern Puget Sound region. Both N. salmincola and POP levels suggest there are adverse health effects on out-migrating steelhead from one southern and one central Puget Sound river that have lower early marine survival than those from a river system in northern Puget Sound.

Cross-sectional study of social behaviors in preschool children and exposure to flame retardants.

BACKGROUND: Children are exposed to flame retardants from the built environment. Brominated diphenyl ethers (BDE) and organophosphate-based flame retardants (OPFRs) are associated with poorer neurocognitive functioning in children. Less is known, however, about the association between these classes of compounds and children's emotional and social behaviors. The objective of this study was to determine if flame retardant exposure was associated with measurable differences in social behaviors among children ages 3-5 years. METHODS: We examined teacher-rated social behaviors measured using the Social Skills Improvement Rating Scale (SSIS) and personal exposure to flame retardants in children aged 3-5 years who attended preschool (n = 72). Silicone passive samplers worn for 7 days were used to assess personal exposure to 41 compounds using gas chromatography-mass spectrophotometer. These concentrations were then summed into total BDE and total OPFR exposure prior to natural log transformation. Separate generalized additive models were used to evaluate the relationship between seven subscales of the SSIS and lnΣBDE or lnΣOPFR adjusting for other age, sex, adverse social experiences, and family context. RESULTS: All children were exposed to a mixture of flame retardant compounds. We observed a dose dependent relationship between lnΣOPFR and two subscales where children with higher exposures were rated by their preschool teachers as having less responsible behavior (p = 0.07) and more externalizing behavior problems (p = 0.03). Additionally, children with higher lnΣBDE exposure were rated by teachers as less assertive (p = 0.007). CONCLUSIONS: We observed a cross-sectional association between children's exposure to flame retardant compounds and teacher-rated social behaviors among preschool-aged children. Children with higher flame retardant exposures exhibited poorer social skills in three domains that play an important role in a child's ability to succeed academically and socially.

Association of Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs) with Hyperthyroidism in Domestic Felines, Sentinels for Thyroid Hormone Disruption.

BACKGROUND: Hyperthyroidism is the most common endocrine disorder observed in domestic felines; however, its etiology is largely unknown. Two classes of persistent organic pollutants, polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are known to interfere with thyroid hormone (TH) signaling and regulation; thus, it is postulated that they contribute to the etiopathogenesis of feline hyperthyroidism and pose a risk to humans and other species. In this case-control study, the concentrations of 13 PBDE and 11 PCB congeners were measured by gas chromatography mass spectrometry in serum or plasma samples from 20 hyperthyroid and 31 control cats in order to investigate the association between concentration of PBDE and PCB congeners and feline hyperthyroidism. Logistic regression analysis was used to determine whether elevated concentrations of individual congeners were associated with a higher risk of feline hyperthyroidism. RESULTS: Hyperthyroid cats had higher concentrations of four PBDE congeners (BDE17, BDE100, BDE47, and BDE49) and five PCB congeners (PCB131, PCB153, PCB174, PCB180, and PCB196), compared to control cats. In addition, the sum of both PBDE and PCB congener concentrations were elevated in the hyperthyroid group compared to control cats; however, only the increased PCB concentrations were statistically significant. The sum total PBDE concentrations in our feline samples were approximately 50 times greater than concentrations previously reported in human populations from a geographically similar area, whereas sum total PCB concentrations were comparable to those previously reported in humans. CONCLUSIONS: These observational findings support the hypothesis that PBDEs and PCBs may contribute to the etiopathogenesis of hyperthyroidism in felines. As domestic house cats are often exposed to higher concentrations of PBDEs than humans, they may serve as sentinels for the risk of TH disruption that these pollutants pose to humans and other species.

[Human exposure and thyroid toxicity of polybrominated diphenyl ethers].

Polybrominated diphenyl ethers (PBDEs), a kind of important Brominated Flame Retardant (BFR), are widely used in electronic products, construction materials and textiles. PBDEs have been detected in many environmental media (including air, water, dust, sediment and food), many animal and human tissues. For their environmental persistence, high bioaccumulative and multiple biotoxicitiies, PBDEs have been viewed as one of the most concerned environmental Endocrine Disrupting Chemicals (EDCs) at present. Although detailed mechanisms are not clear, studies have found that PBDEs can induce toxicity to liver, endocrine system, nervous system, reproduction and immune system. What's more, lots of experiments indicate that PBDEs exposure can alter the levels of thyroid hormones. Recently, studies on the impact of PBDEs exposure on thyroid hormones have been quite a few and have not reached an agreement, especially on the alternation of thyroid hormones caused by PBDEs exposure, which has also been a hot issue. This paper reviews from the basic properties, usage, exposure and biotoxicity of PBDEs. We mainly introduce the impact PBDEs have on the thyroid and thyroid hormones in terms of biotoxicity, and attach importance to the endocrine disruption and neurodeveloptoxicity. We also give a preliminary introduction to hydroxylated and methoxylated polybrominated diphenyl ethers, structural analogs of PBDEs, which researchers start late to study. This paper can be a reference for the further research on PBDEs exposure and biotoxicity.

[Research progress of health effect of polybrominated diphenyl ethers].

Polybrominated diphenyl ethers (PBDEs) was one of the most common brominated flame retardants, it has been widely used in products such as furnitures, polymer and plastical material, textiles, electronic products and building materials. PBDEs have potential effect such as neurodevelopmental toxicity, reproductive toxicity, thyroid toxicity, immunological toxicity, embryo toxicity, liver toxicity, teratogenicity and potential carcinogenicity. This paper was aimed to review the environmental exposure way, current level, neurotoxicity, neurodevelopmental toxicity and reproductive toxicity of PBDEs. In recent years, PBDEs has been detected in environment, wildlife animal and human body around the world, there were the significant differences of exposure levels of PBDEs. The most abundant congener were tetra-BDE or BDE-47, hexa-BDE or BDE-153, and deca-BDE or BDE-209. Prenatal exposure to PBDEs has great impact on the infants' neurodevelopmental function, induces changes in neuropsychological developmental behavior, decreases of congnition, motivation and attention. High levels of PBDEs have positive relationship with Luteinizing hormone levels, testis disfunction and children's cryptorchidism, and have negative relationship with sperm number and testis size.

[Effects of extracellular regulated protein kinases protein and impairment of blood testis barriar stucturein of mice with exposure to decabromodiphenyl ether].

Objective: To study changes in expression of claudin-11 and proteins related to mitogen-activated protein kinase (MAPK) signaling pathways, as well as the ultrastructure of the blood testis barrier (BTB), in male ICR mice exposed to decabromodiphenyl ether (BDE-209). Methods: Fifty-two mice, 4 weeks of age, weighing 15-21 g, were provided with adaptive feeding for 1 week. Mice were randomly divided into 4 groups, named control, low-dose, medium-dose and high-dose groups. The treated groups received BDE-209, by intragastric gavage, at doses, respectively, of 100, 300 and 500 mg/kg. Mice were sacrificed after 6 weeks and organs harvested on ice, weighed and stored at -80 °C. The ultrastructure of testicular tissues was examined by electron microscopy. Western blotting was used to detect proteins related to the MAPK pathway, including p38 mitogen activated protein kinase (p38), phosphorylated p38 (p-p38), extracellular regulated protein kinase 1/2 (ERK1/2) , phosphorylated ERK1/2 (p-ERK1/2) , c-jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK) and the BTB tight junction protein claudin-11. Analyze the difference between each groups. Results: At sacrifice, the body weights in each treated group were compared with those in the control group weighing (41.14 ± 0.60) g. Compared with controls, body weights were significantly different (P<0.05) in the middle dose, at (39.97 ± 0.66) g and high dose, at (39.98± 0.55) g in control group. The coefficients of the testis were significantly lower (P<0.05) in each treated group than in controls, with values of (0.37±0.0)%, (0.31±0.05)% and (0.31±0.04)% for low-dose, medium-dose and high-dose groups, respectively. The epidymus coefficient values were also significantly lower than controls (P<0.05), with values of (0.16±0.06)%, (0.11±0.05)% and (0.07±0.03)%, respectively in the same three dose groups. Electron microscopy ultrastructure showed that, compared with the control group, the testes in the middle and high dose groups had closely connected fractures, cell edema and more vacuoles. Compared with in the control group, levels of p-p38 and p-JNK in testicular tissue were significantly increased (P<0.05). In the control group and in low-, medium- and high-dose groups, the p-p38/p38 ratios were 1.35±0.13, 3.46±0.10, 5.71±0.26 and 4.79±0.21, respectively. The corresponding p-JNK/JNK ratios were 2.07±0.0, 4.77±0.18, 3.63±0.06 and 4.85±0.15. Claudin-11 levels were significantly lower (P<0.05) than control values in each dosed group. The corresponding values in control, low-dose, medium-dose and high-dose groups were 8.33±0.36, 2.06±0.27, 3.37±0.27 and 1.55±0.19, respectively. Conclusion: BDE-209 increased expression of proteins in the MAPK pathway and decreased expression of the BTB tight junction protein claudin-11 in testicular tissue. It also caused ultrastructural damage to the Sertoli cell BTB tight junctions. This suggested that BDE-209 might damage Sertoli cells BTB through effects on the MAPK pathway.

Prenatal exposure to polybrominated diphenyl ethers and polyfluoroalkyl chemicals and infant neurobehavior.

OBJECTIVE: To assess the impact of prenatal exposure to polybrominated diphenyl ethers (PBDEs) and polyfluoroalkyl chemicals (PFCs) on early infant neurobehavior. STUDY DESIGN: In a cohort of 349 mother/infant pairs, we measured maternal serum concentrations during pregnancy of PBDEs, including BDE-47 and other related congeners, as well as 2 common PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid. When the infants were 5 weeks of age, we measured their neurobehavior by using the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS). RESULTS: Neither PBDE nor PFC exposures during gestation were associated with the 11 individual NNNS outcomes included in our study; however, when we used latent profile analysis to categorize infants into neurobehavioral profiles based on performance on the NNNS (social/easygoing, high arousal/difficult, or hypotonic), a 10-fold increase in prenatal PFOA concentrations significantly increased the odds of being categorized as hypotonic compared with social/easygoing (aOR 3.79; 95% CI 1.1-12.8). CONCLUSIONS: Infants of mothers with greater serum concentrations of PFOA during pregnancy were more likely to be categorized as hypotonic. No association between PBDE concentrations and hypotonia was found. Additional studies should further investigate possible associations of prenatal PFC exposure and muscle tone in infants and children.

Prenatal Exposure to Polybrominated Flame Retardants and Fetal Growth in the INMA Cohort (Spain).

Our aim was to investigate the relation between PBDEs and fetal growth or newborn anthropometry in a Spanish cohort (2003-2008). PBDE congeners (BDE-47, -99, -153, -154, and -209) were determined in serum of 670 mothers at gestational week 12 and in 534 umbilical cord samples. Abdominal circumference (AC), estimated fetal weight (EFW), femur length (FL), and biparietal diameter (BPD) during gestation were measured by ultrasounds. At birth, weight (BW), head circumference (HC), and length (BL) were also measured. We assessed growth in the intervals between 12-20 and 20-34 weeks of gestation and size at birth by standard deviation (SD)-scores adjusted for constitutional characteristics. We conducted multivariate linear regression analyses between PBDE congeners and their sum (ΣPBDEs) and outcomes. We found statistically significant inverse associations between ΣPBDEs and AC, EFW, and BPD at weeks 20-34 and HC at birth. Regarding congeners, the association was clearer with BDE-99, with inverse associations being found with AC, EFW, and BPD at weeks 20-34, and with BW and HC at delivery. These outcomes decreased between 1.3% and 3.5% for each 2-fold PBDE increase. Concerning matrices, we found statistically significant inverse associations with BPD, HC, and BW when using maternal serum, and for AC and EFW with cord serum. In conclusion, PBDEs may impair fetal growth in late pregnancy and reduce birth size.