| 1. |
- Alarcon, Sonia, et al.
(författare)
-
Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2 ',3,4,4 ',5,5 '-heptachlorobiphenyl (PCB 180) : A postnatal follow-up study in rats
- 2021
-
Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 109-127
-
Tidskriftsartikel (refereegranskat)abstract
- PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.
|
|
| 2. |
- Ali, Imran, et al.
(författare)
-
Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women.
- 2014
-
Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 134, s. 265-269
-
Tidskriftsartikel (refereegranskat)abstract
- Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk.
|
|
| 3. |
- Ali, Imran, et al.
(författare)
-
Cadmium at nanomolar concentrations activates Raf-MEK-ERK1/2 MAPKs signaling via EGFR in human cancer cell lines.
- 2015
-
Ingår i: Chemico-Biological Interactions. - : Elsevier BV. - 0009-2797 .- 1872-7786. ; 231
-
Tidskriftsartikel (refereegranskat)abstract
- Cadmium (Cd) is an environmental contaminant classified as carcinogenic to humans by the International Agency for Research on Cancer, supported by data from occupational exposure. Environmentally relevant dietary exposure to Cd has recently been associated with osteoporosis and cancers of the prostate, endometrium, and breast in the general population. The low exposure effects have been proposed to result from endocrine modulative properties of Cd, which mimic the physiological actions of estrogen and androgen. However, the mechanism of action of Cd is an unanswered question. We have shown previously, using mouse models, that canonical estrogen receptor signaling is not involved in estrogen mimicry effects of Cd. Instead, low-level Cd exposure stimulated the mitogen-activated protein kinases (MAPKs) ERK1/2 in these mice. Here we investigate further the ERK1/2 MAPK signaling activation by Cd in vitro by using nanomolar concentrations of cadmium chloride (CdCl2) in three different human carcinoma cell lines: HepG2, MCF-7, and ECC-1. The findings also were confirmed in previously collected mouse tissue samples. We show that 10(-8)M levels of CdCl2 activate ERK1/2 (Tyr 204) and the p53 specific ubiquitin ligase Mdm2 (Ser 166) via Raf and MEK by acting through the epidermal growth factor receptor (EGFR). Furthermore, our results suggest that the CdCl2-induced activation of ERK1/2 and Mdm2 may interfere with the p53 response to genotoxic compounds in cancer cell lines. Our data collectively suggest that nanomolar levels of CdCl2 activate Raf-MEK-ERK1/2 via EGFR. We hypothesize that this signaling cascade may be involved in observed low exposure effects of Cd in certain human populations.
|
|
| 4. |
- Ali, Imran, et al.
(författare)
-
Cadmium-induced effects on cellular signaling pathways in the liver of transgenic estrogen reporter mice.
- 2012
-
Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 127:1, s. 66-75
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen-like effects of cadmium (Cd) have been reported in several animal studies, and recent epidemiological findings suggest increased risk of hormone-dependent cancers after Cd exposure. The mechanisms underlying these effects are still under investigation. Our aim was to study the effects of Cd on cellular signaling pathways in vivo with special focus on estrogen signaling and to perform benchmark dose analysis on the effects. Transgenic adult ERE-luciferase male mice were exposed subcutaneously to 0.5-500 μg CdCl(2) per kg body weight (bw) or 17α-ethinylestradiol (EE2) for 3 days. These doses had no effects on organ and bw or testicular histology, indicating subtoxic exposure levels. The transgene luciferase, reporting genomic estrogen response, was significantly increased by EE2 but not by Cd. However, Cd significantly affected kinase phosphorylation and endogenous gene expression. Interestingly, gene expression changes displayed a traditional dose-response relationship, with benchmark dose levels for the expression of Mt1, Mt2, p53, c-fos, and Mdm2 being 92.9, 19.9, 7.6, 259, and 25.9 μg/kg bw, respectively, but changes in kinase phosphorylation were only detected at low exposure levels. Phosphorylation of Erk1/2 was significantly increased even in the lowest dose group, 0.5 μg/kg bw, rendering pErk1/2 a more sensitive sensor of exposure than changes in gene expression. Collectively, our data suggest that the effects triggered by Cd in vivo are markedly concentration dependent. Furthermore, we conclude that the estrogen-like effects of Cd are likely to result from a mechanism different from steroidal estrogens.
|
|
| 5. |
- Ali, Imran, et al.
(författare)
-
Estrogen-like effects of cadmium in vivo do not appear to be mediated via the classical estrogen receptor transcriptional pathway.
- 2010
-
Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 118:10, s. 1389-94
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cadmium (Cd), a ubiquitous food contaminant, has been proposed to be an endocrine disruptor by inducing estrogenic responses in vivo. Several in vitro studies suggested that these effects are mediated via estrogen receptors (ERs). OBJECTIVE: We performed this study to clarify whether Cd-induced effects in vivo are mediated via classical ER signaling through estrogen responsive element (ERE)-regulated genes or if other signaling pathways are involved. METHODS: We investigated the estrogenic effects of cadmium chloride (CdCl2) exposure in vivo by applying the Organisation for Economic Co-operation and Development (OECD) rodent uterotrophic bioassay to transgenic ERE-luciferase reporter mice. Immature female mice were injected subcutaneously with CdCl2 (5, 50, or 500 µg/kg body weight) or with 17α-ethinylestradiol (EE2) on 3 consecutive days. We examined uterine weight and histology, vaginal opening, body and organ weights, Cd tissue retention, activation of mitogen-activated protein kinase (MAPK) pathways, and ERE-dependent luciferase expression. RESULTS: CdCl2 increased the height of the uterine luminal epithelium in a dose-dependent manner without increasing the uterine wet weight, altering the timing of vaginal opening, or affecting the luciferase activity in reproductive or nonreproductive organs. However, we observed changes in the phosphorylation of mouse double minute 2 oncoprotein (Mdm2) and extracellular signal-regulated kinase (Erk1/2) in the liver after CdCl2 exposure. As we expected, EE2 advanced vaginal opening and increased uterine epithelial height, uterine wet weight, and luciferase activity in various tissues. CONCLUSION: Our data suggest that Cd exposure induces a limited spectrum of estrogenic responses in vivo and that, in certain targets, effects of Cd might not be mediated via classical ER signaling through ERE-regulated genes.
|
|
| 6. |
- Ali, Imran, et al.
(författare)
-
From pure compounds to complex exposure : Effects of dietary cadmium and lignans on estrogen, epidermal growth factor receptor, and mitogen activated protein kinase signaling in vivo.
- 2016
-
Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 253
-
Tidskriftsartikel (refereegranskat)abstract
- Exposure to environmental endocrine active compounds correlates with altered susceptibility to disease in human populations. Chemical risk assessment is single compound based, although exposure often takes place as heterogeneous mixtures of man-made and natural substances within complex matrices like diet. Here we studied whether the effects of cadmium and enterolactone on endocrine endpoints in dietary exposure can be predicted based on pure compound effects. Ovariectomized estrogen reporter ERE-luciferase (ERE-luc) mice were maintained on diets that intrinsically contain increasing concentrations of cadmium and enterolactone precursors for three and 21 days. The activation of the ERE-luc, epidermal growth factor receptor (EGFR), mitogen activated protein kinase (MAPK)-ERK1/2, and classical estrogen responses were measured. Interactions between the diets and endogenous hormone were evaluated by challenging the animals with 17β-estradiol. Compared to animals on basal purified diet, mice consuming experimental diets were exposed to significantly higher levels of cadmium and enterolactone, yet the exposure remained comparable to typical human dietary intake. Surprisingly, we could not detect effects on endpoints regulated by pure enterolactone, such as ERE-luc activation. However, cadmium accumulation in the liver was accompanied with activation of EGFR and MAPK-ERK1/2 in line with our earlier CdCl2 studies. Further, attenuation of 17β-estradiol-induced ERE-luc response in liver by experimental diets was observed. Our findings indicate that the exposure context can have substantial effects on the activity of endocrine active compounds in vivo. Thus, whenever possible, a context that mimics human exposure should be tested along with pure compounds.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Axelsson, Jeanette, et al.
(författare)
-
Expression of estrogen receptor-alpha and -beta mRNA in the brain of Japanese quail embryos
- 2007
-
Ingår i: Developmental Neurobiology. - : Wiley. - 1932-8451 .- 1932-846X. ; 67:13, s. 1742-1750
-
Tidskriftsartikel (refereegranskat)abstract
- The present study was conducted to investigate the mRNA expression of the two estrogen receptor (ER) subtypes ERα and ERβ in the brain of Japanese quail embryos. We found expression of both ERα and ERβ mRNA in homogenate of whole head from 6-day-old embryos, and in brain homogenate from 9- and 12-day-old embryos using real-time PCR. In 9- and 12-day-old embryos the ERα expression was higher in females than in males. We used in situ hybridization to examine the localization of the ERs in sections from male and female brains on day 9 and day 17 of incubation. On day 9, ERβ mRNA was detected in the developing medial preoptic nucleus (POM), in the medial part of the bed nucleus of the striae terminalis (BSTm), and in the tuberal region of the hypothalamus. ERα signal could not be detected in the POM, the BSTm or the tuberal region in 9-day-old embryos. In 17-day-old embryos, ERβ was highly expressed in the preoptic area, the nucleus Taeniae of the Amygdala (TnA) and the BSTm. Expression of ERα mRNA was detected in parts of the preoptic area and in the telencephalic TnA. No ERα expression was found in the BSTm, an area known to be sexually dimorphic in adults. The high embryonic expression of ERβ in brain areas linked to sexual behavior indicates that ERβ plays a role in sexual differentiation of the Japanese quail brain.
|
|
| 10. |
|
|
| 11. |
- Berg, Cecilia, et al.
(författare)
-
Methods for studying xenoestrogenic effects in birds
- 1998
-
Ingår i: TOXICOLOGY LETTERS. - 0378-4274. ; 103, s. 671-676
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The embryonated bird egg provides a simple whole organism test system that allows examination of xenoestrogenic effects at different levels of biological organisation. Test compounds are injected into the yolk, the albumen or the air chamber at defined st
|
|
| 12. |
- Bogdanska, Jasna, et al.
(författare)
-
Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose
- 2011
-
Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 284:1-3, s. 54-62
-
Tidskriftsartikel (refereegranskat)abstract
- The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g., hepatotoxicity, immunotoxicity and developmental toxicity. However, detailed information on the tissue distribution of PFOS in mammals is scarce and, in particular, the lack of available information regarding environmentally relevant exposure levels limits our understanding of how mammals (including humans) may be affected. Accordingly, we characterized the tissue distribution of this compound in mice, an important experimental animal for studying PFOS toxicity. Following dietary exposure of adult male C57/BL6 mice for 1-5 days to an environmentally relevant (0.031 mg/kg/day) or a 750-fold higher experimentally relevant dose (23 mg/kg/day) of (35)S-PFOS, most of the radioactivity administered was recovered in liver, bone (bone marrow), blood, skin and muscle, with the highest levels detected in liver, lung, blood, kidney and bone (bone marrow). Following high daily dose exposure, PFOS exhibited a different distribution profile than with low daily dose exposure, which indicated a shift in distribution from the blood to the tissues with increasing dose. Both scintillation counting (with correction for the blood present in the tissues) and whole-body autoradiography revealed the presence of PFOS in all 19 tissues examined, with identification of thymus as a novel site for localization for PFOS and bone (bone marrow), skin and muscle as significant body compartments for PFOS. These findings demonstrate that PFOS leaves the bloodstream and enters most tissues in a dose-dependent manner.
|
|
| 13. |
- Bondesson, Maria, et al.
(författare)
-
A CASCADE of effects of bisphenol A.
- 2009
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 28:4, s. 563-7
-
Tidskriftsartikel (refereegranskat)
|
|
| 14. |
- Borg, Daniel, et al.
(författare)
-
Perinatal tissue distribution of perfluorooctane sulphonate (PFOS) in mice.
- 2009
-
Ingår i: Abstracts of the 46th Congress of the European Societies of Toxicology. - : Elsevier BV. ; 189:SI, s. S147-S147
-
Konferensbidrag (refereegranskat)abstract
- Perfluorooctane sulfonate (PFOS) is an industrial chemical that has been used as a surfactant and surface protector for more than fifty years. It has during the last decade emerged as an environmental contaminant due to its widespread presence in humans and wildlife and its persistant, bioaccumulative and toxic properties. PFOS is developmentally toxic and late in utero exposure in rodents affects neonatal survival and growth. Observed symptoms suggest impaired pulmonary function, but the cause of the mortality has not been clarified. The purpose of this study was to determine the perinatal tissue distribution of S35-labelled PFOS in mice using whole-body autoradiography (WBA) combined with liquid scintillation counting (LSC). Pregnant C57Bl/6 mice were dosed orally on gestation day (GD) 16 and sampled on GD18, GD20 and postnatal day (PND) 1 (dams + pups). The results from the WBA and the LSC were unequivocal. In dams, PFOS accumulated primarily in the liver, but also the lungs contained levels higher than the blood. PFOS was readily transferred to the fetus. At GD18 general PFOS levels were higher in the fetus than in the blood of the corresponding dam with accumulation in the liver. At GD20, general PFOS levels remained higher in the fetus than in the dam, with substantial accumulation also in the lung. The accumulation in the lung persisted at PND1. Our results show that the fetus is exposed to higher levels of PFOS than the dam and point towards the lung being the main perinatal target organ of PFOS.
|
|
| 15. |
- Borg, D., et al.
(författare)
-
Tissue distribution of S-35-labelled perfluorooctane sulfonate (PFOS) in C57Bl/6 mice following late gestational exposure
- 2010
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 30:4, s. 558-565
-
Tidskriftsartikel (refereegranskat)abstract
- Exposure of rodents in utero to perfluorooctane sulfonate (PFOS) impairs perinatal development and survival Following intravenous or gavage exposure of C57Bl/6 mouse dams on gestational day (GD) 16 to S-35-PFOS (12 5 mg/kg) we determined the distribution in dams fetuses (GD18 and GD20) and pups (postnatal day 1 PND1) employing whole-body autoradiography and liquid scintillation counting In dams levels were highest in liver and lungs After placental transfer S-35-PFOS was present on GD18 at 2-3 times higher levels in lungs liver and kidneys than in maternal blood In PND1 pups levels in lungs were significantly higher than in GD18 fetuses A heterogeneous distribution of S-35-PFOS was observed in brains of fetuses and pups with levels higher than in maternal brain This first demonstration of substantial localization of PFOS to both perinatal and adult lungs is consistent with evidence describing the lung as a target for the toxicity of PFOS at these ages.
|
|
| 16. |
|
|
| 17. |
- Brunström, Björn, et al.
(författare)
-
Effects of estrogens on sex differentiation in Japanese quail and chicken
- 2009
-
Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 163:1-2, s. 97-103
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen production by the female avian embryo induces development of a female phenotype of the reproductive organs whereas the low estrogen concentration in the male embryo results in a male phenotype. Treatment of female embryos with exogenous estrogens disrupts Müllerian duct development resulting in malformations and impaired oviductal function. Exposure of male embryos to estrogens results in ovotestis formation and persisting Müllerian ducts in the embryos and testicular malformations, reduced semen production and partially developed oviducts in the adult bird. Furthermore, studies in Japanese quail show that the male copulatory behavior is impaired by embryonic estrogen treatment. Results from our experiments with selective agonists for ERalpha and ERbeta suggest that the effects of estrogens on the reproductive organs are mediated via activation of ERalpha. Abundant expression of ERalpha mRNA was shown in gonads and Müllerian ducts of early Japanese quail embryos. Both ERalpha and ERbeta transcripts were detected by real-time PCR in early embryo brains of Japanese quail indicating that both receptors may be involved in sex differentiation of the brain. However, in 9-day-old quail embryo brains in situ hybridization showed expression of ERbeta mRNA, but not of ERalpha mRNA, in the medial preoptic nucleus (POM) and the bed nucleus of the stria terminalis (BSTm), areas implicated in copulatory behavior of adult male quail. Furthermore, embryonic treatment with the selective ERalpha agonist propyl pyrazol triol (PPT) had no effect on the male copulatory behavior. These results suggest that ERbeta may be important for the effects of estrogens on brain differentiation.
|
|
| 18. |
- Danielsson, Conny, et al.
(författare)
-
Comparison of Levels of PCDD/Fs and non-Ortho PCBs in PCB 153 from seven different suppliers
- 2008
-
Ingår i: Organohalogen Compounds. ; 70, s. 001201-3
-
Tidskriftsartikel (refereegranskat)abstract
- Twelve PCBs with dioxin-like (DL) properties have been carefully studied through the years to facilitate risk assessment and they have been assigned WHO-TEF values [1] based on their relative toxicity and endocrine effects compared to 2,3,7,8-TCDD. From a toxicological point of view, the non-dioxin-like PCBs (NDL-PCBs) are less characterized but usually account for more than 90% of the total mass of PCBs in food samples [2]. Furthermore, over 90% of the NDL-PCB exposure in the general population is via food and the average daily intake can be estimated to be 10-45 ng/kg (bw)/day according to the European Food Safety Authority EFSA [3]. The EFSA committee concluded that a proper risk assessment of this abundant and environmentally significant class of compounds could not be accomplished. In 2006, the European Commission initiated a project which has as its aim to better examine the toxicity of NDL-PCBs: ATHON- "Assessing the toxicity and hazard of nondioxin-like PCBs present in food". The ATHON project will perform all in vivo and in vitro studies with ultra pure PCBs with known levels of DL-PCBs, PCDD/Fs and total TEQ-levels. As a first step in this study the major suppliers of PCB 153 were identified and the aim of the research was to investigate if there were any clear differences in the quality of their products based on possible impurities of PCDD/Fs and non-ortho PCBs. PCB 153 was selected because of its relatively high presence in environmental compartments and biota and since it has been the most frequently studied NDL-PCB in a few major in vivo studies [2]. Impurities of PCDD/Fs and DL-PCBs, even at trace levels, in PCB 153 may make a significant contribution to the effects seen in in vivo studies as the highest concentrations being studied are at mg/g (bw)/day during a period of time. These high daily exposure levels in combination with possible accumulation of toxic impurities may by time pose a threat to the significance of observed effects. Within the ATHON project all NDL-PCBs used for both in vitro and in vivo tests are analyzed and in many cases purified to remove possible traces of PCDD/Fs and non-ortho PCBs.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Halldin, Krister, 1971-
(författare)
-
Endocrine modulators and sexual differentiation in Japanese quail : With emphasis on the neuroendocrine system
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chemical disruption of the endocrine system in various animal species is currently attracting considerable interest, but avian models are not yet widely used in studying endocrine disturbances. This thesis shows the occurrence of alterations in sexual behavior and reproductive organs in adult Japanese quail (Coturnix japonica) following embryonic exposure to estrogen-like chemicals.Exposure to synthetic estrogens and the environmental pollutant o,p´-DDT caused depressed male sexual behavior. Testis weight asymmetry, cloacal gland area and plasma testosterone levels were also changed, albeit not by all compounds. In females, o,p´-DDT caused disturbed egg laying and malformations of the oviducts. The pollutants bisphenol A and tetrabromobisphenol A did not cause estrogen-like effects at the doses tested. Sexual differentiation of the brain in birds is directed by estrogen, and in adult males, sexual behavior is activated by testosterone after local aromatization into estrogen in the brain. Consequently, the expression of estrogen receptors (ERs) is important both during differentiation and for activation of sexual behavior. The localization of ERα and ERβ mRNA in the brain was studied by in situ hybridization in embryos and adults of both sexes. Both receptors were localized in brain areas regulating sexual behavior. No distinct sex differences in localization or density of the mRNAs were found, but ERβ seemed to be present in higher density in the male nucleus taeniae. In embryos, ERβ was detected earlier than ERα, but by the end of incubation, both receptors were shown to be present. In conclusion, it was found that several reproductive variables in adult quail are disturbed by exposure to estrogen-like chemicals during the critical period of sexual differentiation. Sexual behavior was the most sensitive endpoint in males and it is suggested in the thesis that this variable be included in avian in vivo testing for endocrine modulating chemicals. In females, functional and morphological changes of the oviducts are useful endpoints for estrogen-like effects. The roles of ERα and ERβ in normal sexual differentiation in birds and in chemically induced disruptions of this process need to be elucidated further.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Hollert, Henner, et al.
(författare)
-
Biological and Chemical Determination of Dioxin-like Compounds in Sediments by Means of a Sediment Triad Approach in the Catchment Area of the River Neckar
- 2002
-
Ingår i: Ecotoxicology. - 0963-9292 .- 1573-3017. ; 11:5, s. 323-36
-
Tidskriftsartikel (refereegranskat)abstract
- To evaluate the sediment quality of selected sites in the catchment area of the River Neckar, an integrative assessment approach was used to assess the ecological hazard potential of dioxin-like sediment compounds. The approach is based on 7-ethoxyresorufin-O -deethylase (EROD) induction in embryonic chicken liver culture and comprehensive chemical analyses of polycyclic aromatic hydrocarbons (priority PAHs according to the US Environmental Protection Agency). The majority of the sediment extracts exhibited high potencies as EROD-inducers. In one sediment sample, which was influenced by a sewage treatment plant, a very high concentration of 930 ng bioassay 2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD) equivalents (bio-TEQs )/g organic carbon could be determined. However, in none of the samples, more than 6% of the EROD-inducing potency could be explained by the PAHs analyzed chemically. Thus, non-analyzed compounds with EROD-inducing potency were present in the extracts. A fractionation of sediment samples according to pH allowed to localize the major part of EROD-inducing compounds in the neutral fractions. However, a significant portion of the EROD induction could also be explained by the acidic fractions. Following the concept of the Sediment Quality Triad according to Chapman, in situ alterations of macrozoobenthos were examined. A comparison of the results predicted by the EROD assay and chemical analyses with alterations in situ , as measured by means of the saprobic index and the ecotoxicological index according to Carmargo, revealed a high ecological relevance of the results of bioassays and chemical analyses for major sites.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Mattsson, Anna, 1979-
(författare)
-
Roles of ERα and ERβ in Normal and Disrupted Sex Differentiation in Japanese Quail
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Exposure to xenoestrogens during development has been shown to impair sexual differentiation in various species. The major aim of this thesis was to elucidate the respective roles of the two estrogen receptors ERα and ERβ in normal and disrupted differentiation of sex organs and copulatory behavior in the Japanese quail (Coturnix japonica). The expression of ERα mRNA was much stronger than that of ERβ mRNA in the gonads and Müllerian ducts (embryonic oviducts) in early embryos. By contrast, ERβ seemed to be predominantly expressed in regions of the embryonic brain that are associated with male sexual behavior. Embryos were exposed to the selective ERα agonists propyl-pyrazole-triol (PPT) and 16α-lactone-estradiol (16α-LE2). The estrogens 17β-estradiol (E2) and 17α-ethynylestradiol (EE2), which activate both ERα and ERβ, were used as positive controls. All substances impaired reproductive organ differentiation. The effects observed included oviductal malformations in females and partial development of oviducts in males. All substances also induced testis feminization (ovotestis) in male embryos. The male copulatory behavior was severely impaired by the positive controls but was unaffected by PPT and 16α-LE2 at doses that disrupted sex organ differentiation. A higher dose of 16α-LE2 significantly suppressed the behavior. However, it is possible that this effect was caused by cross-activation of ERβ. The substances also induced hepatic expression of mRNA encoding the egg-yolk proteins vitellogenin II and very low-density apolipoprotein II, which are commonly used as indicators of estrogen exposure. In conclusion, the results suggest that ERα is important for female reproductive organ differentiation. Excess activation of ERα by xenoestrogens impairs differentiation in both females and males and induces hepatic expression of egg-yolk proteins. The results also indicate that ERα alone cannot mediate demasculinization of male copulatory behavior in quail, although further studies are needed to test this hypothesis.
|
|
| 32. |
- Mattsson, Anna, et al.
(författare)
-
Selective activation of estrogen receptor alpha in Japanese quail embryos affects reproductive organ differentiation but not the male sexual behavior or the parvocellular vasotocin system
- 2008
-
Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 159:2-3, s. 150-157
-
Tidskriftsartikel (refereegranskat)abstract
- Estradiol is crucial for normal female differentiation in birds. Developmental effects of estrogen are believed to be mediated by slow genomic actions through the nuclear estrogen receptors alpha (ERα) and/or beta (ERβ). Consequently, exogenous compounds that interfere with the ERs may disrupt sexual differentiation of the reproductive organs and of the brain areas controlling sexual behaviors. The present study was conducted to elucidate the role of ERα in xenoestrogen-induced disruption of sexual differentiation in the Japanese quail (Coturnix japonica). Embryonic treatment with the synthetic estrogen, ethinylestradiol (EE2), and with the ERα-selective agonist, propyl pyrazole triol (PPT), induced oviductal malformations in females and retention of oviducts in males. Both EE2 and PPT caused weight asymmetry between left and right testes and reduced the cloacal gland area in males. EE2 significantly reduced the copulatory behavior in males whereas PPT had no effect on this behavior. The sexually dimorphic parvocellular vasotocin-immunoreactive (VT-ir) system in the medial preoptic nucleus (POM), the lateral septum (SL) and the medial part of the nucleus of the stria terminalis (BSTm), was not affected by EE2 or PPT. Our results suggest that xenoestrogen-induced effects on reproductive organ differentiation are mediated by ERα, whereas demasculinization of male copulatory behavior and the VT-ir system appears not to be induced by activation of ERα alone.
|
|
| 33. |
|
|
| 34. |
- Nordén, Marcus, 1982-
(författare)
-
Comparative avian developmental toxicity of PFAAs
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perfluoroalkyl acids (PFAAs) are persistent organic pollutants that can commonly be found in environmental matrixes and wildlife from all over the globe. The PFAAs have been used in applications such as water and dirt repelling treatments for textiles, oil-resistant paper coatings and fire-fighting foams. Four studies were designed to evaluate the occurrence of PFAAs in Swedish populations of birds, the developmental toxicity of different PFAAs and species sensitivity differences as well as possible modes of action for the toxicity. The studied species were domestic chicken, and the wild species great cormorant and herring gull. Cormorant and gull eggs were collected from bird colonies in Lake Vänern, Sweden. Chemical analyses were performed on some of the eggs to determine the occurrence of 15 PFAAs in the eggs. The other eggs and eggs of domestic chicken were incubated and injected with solutions of the PFAAs PFOS, PFOA, PFBS and PFUnDA. The eggs were candled every 1-3 days to determine viability. High levels of PFAAs, mainly PFOS followed by PFUnDA, were found in the herring gull and great cormorant eggs. PFOS was found at concentrations up to 1163 ng/g and 771 ng/g in cormorant and herring gull, respectively. In the toxicity tests, chicken was found to be more sensitive than the wild species and cormorant was in general the least sensitive species. PFOA was found to be the most toxic of the chemicals followed by PFOS, PFBS and PFUnDA in decreasing order. Comparing these results with the levels of these chemicals found in the eggs of herring gull and great cormorant, PFOS is the chemical of most concern. Although PFOA had the highest toxicity, the levels found in the eggs were very low. In an additional study, the hepatic β-oxidation in developing chicken embryos after in ovo exposure to PFOS was studied with a tritium release assay. PFOS was found to increase the β-oxidation of palmitic acid at PFOS concentrations 3-7 times lower than the average egg levels in cormorant and herring gull. Therefore the occurrence of effects on the fatty acid metabolism cannot be ruled out. The doses of effect on embryo survival in the toxicity and the levels found in the herring gulls and cormorants gives a small margin of safety for the wild populations. Continued environmental monitoring and further studies on the toxicity of PFAAs that occur at high environmental concentrations is important.
|
|
| 35. |
- Nordén, Marcus, et al.
(författare)
-
Gene expression analysis of chicken during development subsequent to PFOS and PFOA exposure
- 2010
-
Ingår i: In Vivo. - : International Institute of Anticancer Research. - 0258-851X .- 1791-7549. ; 24:3, s. 358-358
-
Tidskriftsartikel (refereegranskat)abstract
- Perfluorinated compounds have been manufactured for over50 years and have a wide range of applications due to theirsurfactant properties. They have been used as fabricprotectors to repel water and dirt, fire-fighting foams, nonstickcoatings, insecticides and all weather clothing. PFCsare widespread in the environment and are found globally inwildlife. Among the most abundant are perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA). Thelevels in common guillemot eggs from the Baltic Sea areamong the highest found in the Scandinavian environment.Previous studies show effects on embryo survival of chickenat levels close to levels found in the Baltic guillemot. Toinvestigate the possible mechanisms of action, microarraygene expression analysis was conducted. Chicken eggs wereincubated at 37.5 degrees and 60% relative humidity. PFOSor PFOA was administered to eggs on day 4 of incubationby injection into the air cell of the egg. 1 μl injectionsolution per gram egg was used. The injection solutionscontained PFOS or PFOA dissolved at differentconcentrations in sterile water with 5% or 2.5% dimethylsulfoxide respectively. The doses were 10 and 3 mg/kg forPFOS and 1.6 and 0.5 mg/kg for PFOA. The vehiclesolutions were used as control treatment. At day 19 theembryos were sacrificed and the liver was extracted. Four livers per dose and each vehicle control were used. RNA wasextracted from the livers using Qiagen RNeasy Mini Kit.cDNA was synthesized from mRNA and used for microarrayanalysis on Agilent two-color chicken microarrays.
|
|
| 36. |
- Roos, Robert, et al.
(författare)
-
Hepatic effects of a highly purified 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180) in male and female rats.
- 2011
-
Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 284:1-3, s. 42-53
-
Tidskriftsartikel (refereegranskat)abstract
- PCB 180 (2,2',3,4,4',5,5'-heptachlorobiphenyl) is a persistent and accumulating polychlorinated biphenyl abundantly present in food and the environment. In this study, we used highly purified PCB 180 (dioxinlike impurities: 2.7 ng TEQ(WHO)/g PCB 180) in a 28-day toxicity study in young adult Sprague-Dawley rats. Male and female rats were given total doses of 3, 10, 30, 100, 300, 1000 or 1700 mg/kg b.w. PCB 180 by gavage. Increased liver weights were observed at ≥ 300 mg/kg b.w. in males and females. No increases in serum ALT or ALP activities were found. A significant increase in liver pentoxyresorufin O-dealkylase (PROD) activity was found in males at ≥ 10 mg/kg b.w. and in females at ≥ 30 mg/kg b.w. In both genders, a significant induction of hepatic 7-ethoxyresorufin O-deethylase (EROD) activity was also observed in males at ≥ 10 mg/kg b.w. and in females at ≥ 300 mg/kg b.w. Western blotting showed that mainly cytochromes P450 (CYPs) 2B1/2 and 3A1 were induced while slight effects were seen on CYP1A1, CYP1A2 and CYP1B1. However, no induction of CYP1A1, 1A2 and 1B1 was found on the mRNA level, except for a slight effect in females at 1000 mg/kg b.w. Furthermore, hepatic UDP-glucuronosyltransferases (UGTs) 1A1 and 1A6 were markedly induced in males and slightly induced in females. The hepatic concentrations of apolar retinoids were decreased in males at ≥ 30 mg/kg b.w. and in females at ≥ 300 mg/kg b.w. Taken together our findings show that pure PCB 180 leads to hepatic changes in a dose range which did not cause CYP1A1 induction but causes centrilobular liver hypertrophy, affects drug-metabolizing enzymes involved in the metabolism of exogenous and endogenous substrates and leads to changes in liver retinoid levels. A benchmark dose (BMD) approach is presented in order to model lowest effective dose levels for these effects. Comparison of PCB 180 liver level related to BMDL₅ for hepatic hypertrophy in rats with human data on 'total' hepatic PCB levels in individuals without history of specific exposure suggests a relatively small margin of tissue burden in the range of 37-fold. Our results show that the highly pure non dioxin-like PCB 180 exerted strong effects different to dioxin-like compounds and that the low TEQ contamination allowed a characterization of the PCB as non-dioxinlike.
|
|
| 37. |
|
|
| 38. |
- Scholz, Birger, et al.
(författare)
-
Sex-dependent gene expression in early brain development of chicken embryos
- 2006
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 7, s. 12-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms.RESULTS:Using cDNA microarrays and real-time PCR we found gene expression differences between the male and female embryonic brain (or whole head) that may be independent of morphological differentiation of the gonads. Genes located on the sex chromosomes (ZZ in males and ZW in females) were common among the differentially expressed genes, several of which (WPKCI-8, HINT, MHM non-coding RNA) have previously been implicated in avian sex determination. A majority of the identified genes were more highly expressed in males. Three of these genes (CDK7, CCNH and BTF2-P44) encode subunits of the transcription factor IIH complex, indicating a role for this complex in neuronal differentiation.CONCLUSION:In conclusion, this study provides novel insights into sexually dimorphic gene expression in the embryonic chicken brain and its possible involvement in sex differentiation of the nervous system in birds.
|
|
| 39. |
- Viluksela, Matti, et al.
(författare)
-
Toxicological profile of ultrapure 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180) in adult rats.
- 2014
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e104639-
-
Tidskriftsartikel (refereegranskat)abstract
- PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.
|
|
