| 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. |
- Andreucci, Alessandro, et al.
(författare)
-
Cadmium may impair prostate function as measured by Prostate Specific Antigen in semen: a cross-sectional study among European and Inuit men.
- 2015
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 53:Feb 3, s. 33-38
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the association between cadmium in blood and the concentration of the prostate specific antigen (PSA) in semen, including the modifying effects of zinc or the CAG polymorphism in the androgen receptor (AR). Blood and semen samples were collected from 504 partners of pregnant women in Greenland, Poland and Ukraine. We found an inverse trend between cadmium and PSA (log (ß)= -0.121, 95% Confidence Interval (CI):-0.213; -0.029, P=0.0103) in Greenlandic men. Similar results were observed in men with a high number of CAG repeats (CAG 24) (log (ß)=-0.231, 95% CI:-0.363; -0.098, P=0.0009). Inverse trends between cadmium and PSA were found when semen zinc concentrations were below the median value for men from Ukraine and Greenland. These outcomes suggest that cadmium may impair prostate function, as measured by PSA in semen, while high zinc levels and a low number of CAG repeats protects against this action.
|
|
| 3. |
- Baburamani, Ana A, et al.
(författare)
-
Microglia toxicity in preterm brain injury
- 2014
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 48, s. 106-112
-
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.
|
|
| 4. |
- Bereketoglu, Ceyhun, et al.
(författare)
-
The brominated flame retardants TBECH and DPTE alter prostate growth, histology and gene expression patterns in the mouse
- 2021
-
Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 43-55
-
Tidskriftsartikel (refereegranskat)abstract
- The brominated flame retardants (BFRs), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) bind to the androgen receptor (AR). In vitro bioassays have shown that TBECH is a potent androgen agonist while DPTE is a potent AR antagonist. Both TBECH and DPTE alter gene expression associated with AR regulation. However, it remains to be determined if TBECH and DPTE can affect the prostate. For this reason, we exposed CD1 mice to a 1:1 mixture of TBECH diastereomers α and β, a 1:1 mixture of γ and δ, and to DPTE, and tested their effects on prostate growth, histology and gene expression profiles. Castrated (C) mice were used to study the androgenic effects of TBECHαβ and TBECHγδ while the antagonistic effects of DPTE were studied in non-castrated (NC) mice. We observed that testosterone and TBECHγδ increased body and prostate weights while TBECHαβ affected neither of them; and that DPTE had no effect on body weight but reduced prostate weight drastically. Histomorphometric analysis of the prostate revealed epithelial and glandular alterations in the TBECHγδ group comparable to those in testosterone group while alterations in the TBECHαβ group were less pronounced. DPTE displayed androgen antagonist activity reminiscent of castration. The transcription profile of the prostate was altered by castration and exposure to testosterone and to TBECHγδ reversed several of these changes. Testosterone and TBECHγδ also regulated the expression of several androgen responsive genes implicated in prostate growth and cancer. While DPTE resulted in a drastic reduction in prostate weight, it only affected a small number of genes. The results indicate that TBECHγδ and DPTE are of high human health concern as they may contribute to changes in prostate growth, histology and function.
|
|
| 5. |
- Beronius, Anna, et al.
(författare)
-
Risk to all or none? A comparative analysis of controversies in the health risk assessment of Bisphenol A
- 2010
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 29:2, s. 132-146
-
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.
|
|
| 6. |
- Björk, Christel, et al.
(författare)
-
Androgen receptor CAG repeat length modifies the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor activity in human prostate cells.
- 2012
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238.
-
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.
|
|
| 7. |
- Björk, Christel, et al.
(författare)
-
Persistent organic pollutants have dose and CAG repeat length dependent effects on androgen receptor activity in vitro
- 2011
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 32, s. 293-297
-
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.
|
|
| 8. |
- 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)
|
|
| 9. |
- 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.
|
|
| 10. |
- Bredhult, Carolina, et al.
(författare)
-
Effects of some endocrine disruptors on the proliferation and viability of human endometrial endothelial cells in vitro
- 2007
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 23:4, s. 550-559
-
Tidskriftsartikel (refereegranskat)abstract
- Endocrine disrupting chemicals (EDCs) pose a potential threat to human reproductive health. We studied the proliferation and viability of human endometrial endothelial cells (HEECs) in vitro after exposure to 2,2-bis(o,p-chlorophenyl)-1,1,1-trichloroethane (o,p′-DDT), 3,3′,4,4′-tetrachlorobiphenyl (CB 77), 3,3′,4,4′,5-pentachlorobiphenyl (CB 126), di-n-butyl phthalate (DBP), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and 17β-oestradiol, progesterone, 17α-ethynyl oestradiol and levonorgestrel. Cell proliferation was studied using immunocytochemistry for PCNA expression and a 5-bromo-2′-deoxyuridine assay. Cell viability was studied by vital staining with propidium iodide and Hoechst 33258. HEECs in primary culture responded with increased proliferation to oestradiol and with decreased proliferation to levonorgestrel and the EDCs. Some EDCs also affected cell viability and increased the proportion of necrotic cells. However, the decrease in proliferation in response to DBP and TCDD cannot be explained by cell death. In light of these results, it is possible that the EDCs could have effects in vivo as well as in vitro, and influence processes involving for example endometrial angiogenesis.
|
|
