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PCBs (1336-36-3)

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The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Effect of 2,3',4,4',5-pentachlorobiphenyl exposure on endometrial receptivity and the methylation of HOXA10

Authors: Qu, XL; Ming-Zhang; Yuan-Fang; Wang, H; Zhang, YZ (2018) Reproductive Sciences 25:256-268. HERO ID: 3982693

[Less] Polychlorinated biphenyls (PCBs) are one of the most common endocrine-disrupting chemicals and have . . . [More] Polychlorinated biphenyls (PCBs) are one of the most common endocrine-disrupting chemicals and have obvious toxicity on human reproductive development. The aim of our study was to investigate the toxicity of chronic 2,3',4,4',5-pentachlorobiphenyl (PCB 118) exposure on embryo implantation and endometrial receptivity, with the possible mechanism of DNA methylation involved. Virgin CD-1 female mice (3 weeks old) were housed and orally treated with PCB 118 (0, 1, 10, 100 μg/kg) for a month. After mating with fertile males, the pregnant mice were killed on gestation day 4.5. Compared with the control group, implantation failures were observed in 1 μg/kg PCB 118- and 100 μg/kg PCB 118-treated groups. Abnormal endometrial morphology with open uterine lumens and densely compact stromal cells and poorly developed pinopodes were substantially in response to PCB 118 doses above, as well as the significant downregulation of implantation-associated genes (estrogen receptor 1, homeobox A10 [HOXA10], integrin subunit beta 3) and hypermethylation in the promoter region of HOXA10 further. It was confirmed that chronic exposure to PCB 118 produced an increased number of implantation failures in association with a defective uterine morphology during the implantation period. Alterations in methylation of HOXA10 could explain, at least in part, the mechanism of effects of PCB 118 exposure on the implantation process.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Impact of lactational exposure to polychlorinated biphenyl causes epigenetic modification and impairs sertoli cells functional regulators in F1 progeny

Authors: Priya, ES; Kumar, TS; Singh, PR; Balakrishnan, S; Arunakaran, J (2018) Reproductive Sciences 25:818-829. HERO ID: 3984976

[Less] Polychlorinated biphenyl (PCB) is an endocrine-disrupting chemical. Sertoli cells (SCs) provide physical . . . [More] Polychlorinated biphenyl (PCB) is an endocrine-disrupting chemical. Sertoli cells (SCs) provide physical and nutritional support for developing germ cells. Dysfunction in SCs has adverse effects on spermatogenesis. Previously, we found that the lactational exposure of PCBs (1, 2, and 5 mg/kg birth weight/day, orally from postnatal days 1 to 20) decreased the follicle-stimulating hormone receptor (FSHR) and androgen receptor (AR) expression in SCs of F1 progeny. Transcription factors initiate and regulate the transcription of genes. DNA methylation plays an important role in epigenetic gene regulation. Hence, this study was aimed to identify the level of transcription factors regulating FSHR, AR gene expression, and DNA methylation in the promoter of these genes in SCs of both F1 prepuberal and puberal offspring. DNA methylation in the promoter of FSHR and AR genes was examined by sodium bisulfite conversion technique. The protein levels of transcription factors (steroidogenic factor 1 [SF1], upstream stimulatory factors 1 and 2, c-fos, c-jun, and CREB-binding protein) and enzymes DNA methyltransferases (Dnmt1, Dnmt3ab, Dnmt3l, and histone deacetylase 1 [HDAC1]) were analyzed by Western blotting. The transcription factors that regulate the FSHR and AR gene in SCs were decreased in both the PCB-exposed F1 progeny. Methylation was observed in the promoter of FSHR, AR, and SF1. The protein levels of Dnmt1, Dnmt3ab, Dnmt3l, and HDAC1 were increased in the PCBs-treated groups. Subsequently, it leads to transcriptional repression of the genes in SCs. Our finding suggests that PCBs caused epigenetic change in SCs, thereby it impaired SCs function in F1 progeny.

Journal Article
Journal Article

Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-κB signaling via downregulation of HNF1b

Authors: Wu, H; Yu, W; Meng, F; Mi, J; Peng, J; Liu, J; Zhang, X; Hai, C; Wang, X (2017) Redox Biology 12:300-310. HERO ID: 3872275

[Less] Polychlorinated biphenyls (PCB) is a major type of persistent organic pollutants (POPs) that act as . . . [More] Polychlorinated biphenyls (PCB) is a major type of persistent organic pollutants (POPs) that act as endocrine-disrupting chemicals. In the current study, we examined the mechanism underlying the effect of PCB-153 on glucose and lipid metabolism in vivo and in vitro. We found that PCB-153 induced per se and worsened high fat diet (HFD)-resulted increase of blood glucose level and glucose and insulin intolerance. In addition, PCB-153 induced per se and worsened HFD-resulted increase of triglyceride content and adipose mass. Moreover, PCB-153 concentration-dependently inhibited insulin-dependent glucose uptake and lipid accumulation in cultured hepatocytes and adipocytes. PCB-153 induced the expression and nuclear translocation of p65 NF-κB and the expression of its downstream inflammatory markers, and worsened HFD-resulted increase of those inflammatory markers. Inhibition of NF-κB significantly suppressed PCB-153-induced inflammation, lipid accumulation and decrease of glucose uptake. PCB-153 induced oxidative stress and decreased hepatocyte nuclear factor 1b (HNF1b) and glutathione peroxidase 1 (GPx1) expression in vivo and in vitro. Overexpression of HNF1b increased GPx1 expression, decreased ROS level, decreased Srebp1, ACC and FAS expression, and inhibited PCB-153-resulted oxidative stress, NF-κB-mediated inflammation, and final glucose/lipid metabolic disorder. Our results suggest that dysregulation of HNF1b/ROS/NF-κB plays an important role in PCB-153-induced glucose/lipid metabolic disorder.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Detection of 3,3'-dichlorobiphenyl in human maternal plasma and its effects on axonal and dendritic growth in primary rat neurons

Authors: Sethi, S; Keil, KP; Chen, H; Hayakawa, K; Li, X; Lin, Y; Lehmler, HJ; Puschner, B; Lein, PJ (2017) Toxicological Sciences 158:401-411. HERO ID: 3982690

[Less] 3,3'-Dichlorobiphenyl (PCB 11), a byproduct of pigment production, is increasingly detected in environmental . . . [More] 3,3'-Dichlorobiphenyl (PCB 11), a byproduct of pigment production, is increasingly detected in environmental samples. While more highly chlorinated PCB congeners are known developmental neurotoxicants, nothing is known about the potential developmental neurotoxicity of PCB 11. To address this critical data gap, we measured PCB 11 levels in human maternal plasma and quantified the effects of PCB 11 and its major metabolites on morphometric parameters of neuronal connectivity in cultured primary neurons. Mass spectrometry analyses of plasma from 241 pregnant women enrolled in the MARBLES study (University of California, Davis) detected PCB 11 in all samples at concentrations ranging from 0.005 ng/ml to 1.717 ng/ml. Morphometric analyses of primary neuron-glia co-cultures dissociated from the neocortices or hippocampi of neonatal Sprague Dawley rats exposed to vehicle or concentrations ranging from 1 attamolar (aM) to 1 micromolar (µM) of PCB 11, OH-PCB 11, or PCB 11 sulfate indicated that PCB 11 and both metabolites significantly increased axonal and dendritic growth in cortical and hippocampal pyramidal neurons. PCB 11 significantly altered neuronal morphogenesis at concentrations as low as 1 femtomolar (fM), which is approximately 0.22 ng/ml. These data suggest the potential for the developing human brain to be exposed to PCB 11, and demonstrate that environmentally relevant levels of PCB 11 alter axonal and dendritic growth in neuronal cell types critically involved in cognitive and higher-order behaviors. These findings identify PCB 11 as a potential environmental risk factor for adverse neurodevelopmental outcomes in humans.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Polychlorinated biphenyls target Notch/Dll and VEGF R2 in the mouse placenta and human trophoblast cell lines for their anti-angiogenic effects

Authors: Kalkunte, S; Huang, Z; Lippe, E; Kumar, S; Robertson, LW; Sharma, S (2017) Scientific Reports 7:39885. HERO ID: 3982742

[Less] The intrauterine environment is particularly vulnerable to environmental exposures. We previously established . . . [More] The intrauterine environment is particularly vulnerable to environmental exposures. We previously established a mouse model that provided evidence for pregnancy complications and placental anti-angiogenesis in response to Aroclor 1254 (A-1254), a mixture of polychlorinated biphenyls (PCBs). Importantly, these effects were observed in IL-10(-/-), but not wild type, mice, suggesting that IL-10 deficiency predisposes to pregnancy disruptive effects of environmental toxicants. However, the mechanisms by which PCBs cause anti-angiogenic effects are unclear. Here, we evaluated PCB-mediated anti-angiogenic effects by diverse but complementary approaches, including HUVEC-mediated trophoblast invasion in nude mice, in vitro three-dimensional capillary tube formation involving HUVEC and/or HTR8 trophoblasts, and aortic ring endothelial cell outgrowth/sprouting. Taken together, our data suggest that PCBs act as potent anti-angiogenic agents. Importantly, we show that treatment of pregnant IL-10(-/-) mice with A-1254 resulted in placental activation of the Notch/Delta-like ligand (Dll) pathway, a master regulator of cell-cell interaction and vascular patterning. Similar results were obtained with HUVEC and HTR8 trophoblasts. Rescue of A-1254-induced disruption of HUVEC-based tube formation by γ-secretase inhibitor L1790 confirmed the critical role of the Notch/Dll pathway. Our data suggest that PCBs impart pregnancy disruptive functions by activating the Notch/Dll pathway and by inducing anti-angiogenic effects at the maternal-fetal interface.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Polychlorinated biphenyls disrupt hepatic epidermal growth factor receptor signaling

Authors: Hardesty, JE; Wahlang, B; Falkner, KC; Clair, HB; Clark, BJ; Ceresa, BP; Prough, RA; Cave, MC (2017) Xenobiotica 47:807-820. HERO ID: 3983528

[Less] 1. Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that disrupt hepatic xenobiotic . . . [More] 1. Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that disrupt hepatic xenobiotic and intermediary metabolism, leading to metabolic syndrome and nonalcoholic steatohepatitis (NASH).
2. Since phenobarbital indirectly activates Constitutive Androstane Receptor (CAR) by antagonizing growth factor binding to the epidermal growth factor receptor (EGFR), we hypothesized that PCBs may also diminish EGFR signaling.
3. The effects of the PCB mixture Aroclor 1260 on the protein phosphorylation cascade triggered by EGFR activation were determined in murine (in vitro and in vivo) and human models (in vitro). EGFR tyrosine residue phosphorylation was decreased by PCBs in all models tested.
4. The IC50 values for Aroclor 1260 concentrations that decreased Y1173 phosphorylation of EGFR were similar in murine AML-12 and human HepG2 cells (∼2-4 μg/mL). Both dioxin and non-dioxin-like PCB congeners decreased EGFR phosphorylation in cell culture.
5. PCB treatment reduced phosphorylation of downstream EGFR effectors including Akt and mTOR, as well as other phosphoprotein targets including STAT3 and c-RAF in vivo.
6. PCBs diminish EGFR signaling in human and murine hepatocyte models and may dysregulate critical phosphoprotein regulators of energy metabolism and nutrition, providing a new mechanism of action in environmental diseases.

Journal Article
Journal Article

Independent Maternal and Fetal Genetic Effects on Midgestational Circulating Levels of Environmental Pollutants

Authors: Traglia, M; Croen, LA; Lyall, K; Windham, GC; Kharrazi, M; Delorenze, GN; Torres, AR; Weiss, LA (2017) 7:1287-1299. HERO ID: 3926503

[Less] Maternal exposure to environmental pollutants could affect fetal brain development and increase autism . . . [More] Maternal exposure to environmental pollutants could affect fetal brain development and increase autism spectrum disorder (ASD) risk in conjunction with differential genetic susceptibility. Organohalogen congeners measured in maternal midpregnancy blood samples have recently shown significant, but negative associations with offspring ASD outcome. We report the first large-scale maternal and fetal genetic study of the midpregnancy serum levels of a set of 21 organohalogens in a subset of 790 genotyped women and 764 children collected in California by the Early Markers for Autism (EMA) Project. Levels of PCB (polychlorinated biphenyl) and PBDE (polybrominated diphenyl ether) congeners showed high maternal and fetal estimated SNP-based heritability (h(2)g ) accounting for 39-99% of the total variance. Genome-wide association analyses identified significant maternal loci for p,p'-DDE (P = 7.8 × 10(-11)) in the CYP2B6 gene and for BDE-28 (P = 3.2 × 10(-8)) near the SH3GL2 gene, both involved in xenobiotic and lipid metabolism. Fetal genetic loci contributed to the levels of BDE-100 (P = 4.6 × 10(-8)) and PCB187 (P = 2.8 × 10(-8)), near the potential metabolic genes LOXHD1 and PTPRD, previously implicated in neurodevelopment. Negative associations were observed for BDE-100, BDE153, and the sum of PBDEs with ASD, partly explained by genome-wide additive genetic effects that predicted PBDE levels. Our results support genetic control of midgestational biomarkers for environmental exposures by nonoverlapping maternal and fetal genetic determinants, suggesting that future studies of environmental risk factors should take genetic variation into consideration. The independent influence of fetal genetics supports previous hypotheses that fetal genotypes expressed in placenta can influence maternal physiology and the transplacental transfer of organohalogens.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Aroclor1254 disrupts the blood-testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway

Authors: Jia, X; Xu, Y; Wu, W; Fan, Y; Wang, G; Zhang, T; Su, W (2017) Cell Death & Disease 8:e2823. HERO ID: 3984521

[Less] The blood-testis barrier (BTB) constituted by coexisting junction apparatus between Sertoli cells (SCs) . . . [More] The blood-testis barrier (BTB) constituted by coexisting junction apparatus between Sertoli cells (SCs) plays an important role in spermatogenesis, which is a known target of various environmental toxicants. The commercial polychlorinated biphenyls mixture, Aroclor1254, has been shown to impair male reproduction by decreasing sperm count and affecting SC metabolism. This study was designed to investigate the effects of Aroclor1254 on the BTB integrity and elucidate the underlying mechanisms. We found that Aroclor1254 treatment in rats (1 or 3 mg/kg per day for 21 consecutive days) and in primary cultured SCs (5 or 10 μg/ml for 48 h) could induce BTB disruption via p38 MAPK pathway, concurrently with increments in junction proteins (JAM-A, N-cadherin, and β-catenin) endocytosis, and occludin ubiquitination. Either inhibition of caveolin-dependent membrane protein internalization by cholesterol oxidase or silencing E3 ubiquitine ligase Itch by small interfering RNA could partially counteract the effects of Aroclor1254 on the barrier function of cultured SCs. These results demonstrate that Aroclor1254 disrupts the BTB function by promoting the caveolin-dependent endocytosis and ubiquitine-proteasome degradation of junction proteins through the p38 MAPK pathway, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Effects of Aroclor 1254 on the DNA methylation of imprinted genes in the adult mouse sperm

Authors: Wang, CY; Cui, JT; Lu, ZL; Ma, XL; Wang, JH; Sun, YC (2017) Applied Ecology and Environmental Research 15:999-1012. HERO ID: 3985579

[Less] As estrogen-like and anti- androgenic endocrine-disrupting chemicals, polychlorinated biphenyls have . . . [More] As estrogen-like and anti- androgenic endocrine-disrupting chemicals, polychlorinated biphenyls have been reported to affect the male reproductive axis resulting in infertility. In the present study, Aroclor 1254 was administered to adult male mice, and its possible effects on the differentially methylated regions of two paternally (H19 and Gtl2) and three maternally (Mest, Snrpn and Igf2r) imprinted genes were tested in the sperm DNA. In the control, the percentages of methylated CpGs were close to 100% and 0% in paternally or maternally imprinted genes respectively. Aroclor 1254 significantly decreased the percentages of methylated CpGs of H19 and Gtl2 and markedly increased those of Mest, Snrpn, and Igf2r. In addition, dramatically increased mRNA expression of estrogen receptor alpha and beta were obtained in the treatment. We postulate that the effects of PCBs on male spermatogenesis and fertility rates might involve imprinting alterations in the sperm.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Persistent Organic Pollutants Impair Insulin Secretory Function of Pancreatic Beta-Cells: Human and in Vitro Evidence

Authors: Lee, YM; Ha, CM; Kim, SA; Thoudam, T; Yoon, YR; Kim, DJ; Kim, HC; Moon, HB; Park, S; Lee, IK; Lee, DH (2017) Diabetes 66:2669-2680. HERO ID: 3861018

[Less] Persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated . . . [More] Persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), have emerged as a new risk factor of type 2 diabetes (T2D). We evaluated whether chronic exposure to low-dose POPs affects insulin secretory function of beta-cells in humans and in vitro cells. Serum concentrations of OCPs and PCBs were measured in 200 nondiabetic adults. Mathematical-model-based insulin secretion indices were estimated using a 2-hour 7-sample oral glucose tolerance test. Insulin secretion by INS1E beta-cells was measured after 48-hour treatment with 3 OCPs or a PCB mixture. Static second-phase insulin secretion significantly decreased with increasing serum concentrations of OCPs. Adjusted means were 63.2, 39.3, 44.1, 39.3, 39.7, and 22.3 across six categories of a summary measure of OCPs (Ptrend = 0.02). Dynamic first-phase insulin secretion remarkably decreased only among insulin-sensitive individuals with increasing concentrations of OCPs (Ptrend = 0.02); the insulin levels among subjects with high OCPs were about 30% of those with low OCPs. Compared to OCPs, PCBs showed weaker associations. The decreased insulin secretion by INS1E beta-cells was observed for even 1 pM OCPs. Our data from human subjects and in vitro cell experiments suggest that chronic exposure to low-dose POPs, especially OCPs, can induce pancreatic beta-cell dysfunction.