| 1. |
- Baburamani, Ana A, et al.
(författare)
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Microglia toxicity in preterm brain injury
- 2014
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 48, s. 106-112
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Tidskriftsartikel (refereegranskat)abstract
- Microglia are the resident phagocytic cells of the central nervous system. During brain development they are also imperative for apoptosis of excessive neurons, synaptic pruning, phagocytosis of debris and maintaining brain homeostasis. Brain damage results in a fast and dynamic microglia reaction, which can influence the extent and distribution of subsequent neuronal dysfunction. As a consequence, microglia responses can promote tissue protection and repair following brain injury, or become detrimental for the tissue integrity and functionality. In this review, we will describe microglia responses in the human developing brain in association with injury, with particular focus on the preterm infant. We also explore microglia responses and mechanisms of microglia toxicity in animal models of preterm white matter injury and in vitro primary microglia cell culture experiments. © 2014 The Authors.
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| 2. |
- Beronius, Anna, et al.
(författare)
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Risk to all or none? A comparative analysis of controversies in the health risk assessment of Bisphenol A
- 2010
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 29:2, s. 132-146
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA) is an endocrine disruptor for which health risk assessment has proven controversial. Conclusions regarding health risks of BPA vary between assessments from "there is no risk to any part of the population" to "there is risk to the entire population". We have carried out a literature study investigating what might be the scientific and/or policy-related reasons for these differences. Ten risk assessments for BPA were scrutinized and several factors were compared between assessments, including estimations of exposure levels, identification of critical study and NOAEL, assessment factors and significance attributed to reports of low-dose effects. Differences in conclusions were mainly influenced by the evaluation of low-dose effects and the uncertainties surrounding the significance of these data for health risk assessment. The results illustrate the impact of differences in risk assessment policy and expert judgment on the risk assessment process and highlight the importance of transparency in this process.
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| 3. |
- Björk, Christel, et al.
(författare)
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Androgen receptor CAG repeat length modifies the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor activity in human prostate cells.
- 2012
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238.
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Tidskriftsartikel (refereegranskat)abstract
- Increased incidence of prostate cancer has been reported in men exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD acts through the aryl hydrocarbon receptor (AhR), which interacts with the androgen receptor (AR). The AR gene contains a polymorphic CAG repeat that influences its transcriptional activity. We investigated the influence of TCDD on prostate cancer cells (PC-3) and non-tumor prostate cells (PNT1A) on 5α-dihydrotestosterone-activated ARs containing CAG repeats within normal length range (16, 22, and 28). The AhR target gene CYP1A1 mRNA expression was induced by TCDD, but was not affected by the AR CAG length. TCDD had no effect on AR activity in PC-3 cells, whereas the shortest AR variant was induced by TCDD in PNT1A cells. In conclusion, the CAG length dependent effect of TCDD on AR activity in PNT1A, but not in PC-3 cells, indicates as a cell-specific effect of TCDD on AR activity.
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| 4. |
- Björk, Christel, et al.
(författare)
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Persistent organic pollutants have dose and CAG repeat length dependent effects on androgen receptor activity in vitro
- 2011
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 32, s. 293-297
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the effect of exposure to persistent organic pollutants (POPS) on sperm concentration was only seen in men with a short androgen receptor (AR) gene CAG repeat. In order to investigate whether these effects could be observed also in vitro, we tested the impact of 2,2’,4,4’,5,5’-hexachlorobiphenyl (CB-153) and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (4,4’-DDE) on 5 alpha-dihydrotestosterone activated ARs containing 16,22 and 28 CAG repeats, respectively. Single exposure to 4,4’-DDE had the most pronounced effect on the AR activity containing 16 CAG repeats, whereas 28 CAG was the most sensitive variant when a mixture of the two compounds was added. Thus, our in vitro results have confirmed the in vivo data indicating a CAG repeat length dependent effect of endocrine disrupters on the AR activity.
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| 5. |
- Borg, D., et al.
(författare)
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Tissue distribution of S-35-labelled perfluorooctane sulfonate (PFOS) in C57Bl/6 mice following late gestational exposure
- 2010
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 30:4, s. 558-565
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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.
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| 6. |
- Brokken, Leon, et al.
(författare)
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Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality.
- 2014
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 49:Jul 30, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) may affect male reproductive function. Many dioxin-like POPs exert their effects by activation of the aryl hydrocarbon receptor (AHR) signalling pathway. We analysed whether gene-environment interactions between polymorphisms in AHR (R554K) and AHR repressor (AHRR P185A) and serum levels of markers of POP exposure 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) are associated with 21 parameters of male reproductive function in 581 proven-fertile European and Greenlandic men. In Greenlandic men, AHR variants significantly modified the association between serum levels of both p,p'-DDE and CB-153 and inhibin B levels, sperm chromatin integrity, and seminal zinc levels. In the total cohort, interactions between AHRR variants and serum levels of CB-153 were associated with sperm chromatin integrity and the expression of the pro-apoptotic marker protein Fas. The data indicate that susceptibility to adverse effects of POP exposure on male reproductive function is dependent on polymorphisms in genes involved in AHR signalling.
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| 7. |
- Carlsson, Gunnar, et al.
(författare)
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Developmental toxicity of albendazole and its three main metabolites in zebrafish embryos
- 2011
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 32, s. 129-137
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Tidskriftsartikel (refereegranskat)abstract
- Albendazole (ABZ) is used as an anthelmintic drug in humans and animals. ABZ has been shown to cause developmental toxicity in experimental animals, however it is not clear if this is caused by the parent compound or a metabolite. Zebrafish embryos were exposed from 1 to 144 hpf (hours post fertilization) to investigate the developmental toxicity of ABZ, the first metabolite albendazole sulphoxide and the subsequent metabolites albendazole sulphone (ABZSO(2)) and albendazole-2-aminosulphone (ABZSO(2)NH(2)). The results showed that ABZ caused malformations of head and tail and embryonic lethality from 0.3 mu M. In contrast, the metabolites did not display developmental toxicity at any tested concentration. Dechorionation did not influence the developmental toxic potential of ABZ and ABZSO, indicating that bioavailability was not a limiting factor. Chemical analysis showed that at sublethal concentrations, most of ABZ was metabolized to ABZSO. The results demonstrate that in zebrafish embryos ABZ rather than ABZSO displays developmental toxicity. (C) 2011 Elsevier Inc. All rights reserved.
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| 8. |
- Danielsson, Bengt, et al.
(författare)
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Use of ondansetron during pregnancy and congenital malformations in the infant.
- 2014
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 50, s. 134-137
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Tidskriftsartikel (refereegranskat)abstract
- The study investigates teratogenic risks with ondansetron (Zofran(®)). Data from the Swedish Medical Birth Register combined with the Swedish Register of Prescribed Drugs were used to identify 1349 infants born of women who had taken ondansetron in early pregnancy, 1998-2012. Presence of congenital malformations in the offspring was identified with three national health registers. In a Mantel-Haenszel analysis adjustment was made for year of delivery, maternal age, parity, smoking in early pregnancy and pre-pregnancy body mass index. Risks were expressed as odds or risk ratios with 95% confidence intervals. No statistically significantly increased risk for a major malformation was found. The risks for a cardiovascular defect and notably a cardiac septum defect were increased and statistically significant (OR=1.62, 95% CI 1.04-2.14, and RR 2.05, 95% CI 1.19-3.28, respective). The teratogenic risk with ondansetron is low but an increased risk for a cardiac septum defect is likely.
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| 9. |
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| 10. |
- Gardner, Renee M., et al.
(författare)
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Arsenic methylation efficiency increases during the first trimester of pregnancy independent of folate status
- 2011
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 31:2, s. 210-218
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to inorganic arsenic during pregnancy may negatively influence the offspring, though efficient metabolism of arsenic to dimethylarsinic acid (DMA) likely reduces the health risks. This study aimed to evaluate methylation of arsenic over the entire pregnancy and the influence of nutritional status. We studied longitudinally the arsenic metabolite pattern in the urine of 324 pregnant women exposed to arsenic via drinking water and food in rural Bangladesh. Metabolism of arsenic to DMA increased markedly over the course of pregnancy, with the greatest improvement occurring in the first trimester, along with a marked decrease in the most risk-associated monomethylated metabolite. This improvement in methylation was not associated with nutritional status, including vitamin B(12) and folate. Efficient methylation to DMA was associated with improved urinary excretion of arsenic, relative to blood arsenic concentrations, indicating that micronutrient-independent up-regulation of arsenic metabolism already in early pregnancy may provide protection for the fetus.
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