| 1. |
- Bondesson, Maria, et al.
(author)
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A CASCADE of effects of bisphenol A.
- 2009
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 28:4, s. 563-7
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Journal article (peer-reviewed)
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| 2. |
- Bredhult, Carolina, et al.
(author)
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Effects of some endocrine disruptors on the proliferation and viability of human endometrial endothelial cells in vitro
- 2007
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 23:4, s. 550-559
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Journal article (peer-reviewed)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.
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| 3. |
- Bredhult, Carolina, et al.
(author)
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Gene expression analysis of human endometrial endothelial cells exposed to Bisphenol A
- 2009
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 28:1, s. 18-25
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Journal article (peer-reviewed)abstract
- Bisphenol A (BPA) can affect reproductive tissues in several species. Recently, treatment of human endometrial endothelial cells (HEECs) with 100 microM BPA decreased their proliferation and viability. In the present study, 50 microM BPA decreased HEEC proliferation, and microarray analyses of five HEEC cultures revealed that BPA affected biological processes associated with proliferation. Expression of three of the most differentially expressed genes identified in the gene array analysis, SPBC25, SGOL2 and CDCA8, was verified by real-time qRT-PCR in five HEEC cultures obtained from women in the proliferative phase and in five cultures obtained from women in the secretory phase of the menstrual cycle after treatment with BPA. This study supports our previous findings of decreased cell proliferation and increased cell death in response to BPA, and may offer important clues to the mechanisms of action of BPA. Furthermore, the study implies a possible impact of BPA on female fertility functions.
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| 4. |
- Bredhult, Carolina, et al.
(author)
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Study of the relation between the incidence of uterine leiomyomas and the concentrations of PCB and DDT in Baltic gray seals
- 2008
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 25:2, s. 247-255
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Journal article (peer-reviewed)abstract
- Exposure to environmental contaminants is believed to be associated with the previously described decrease in the reproduction rate of Baltic gray seals. In the present study the prevalence of uterine leiomyomas was investigated in 257 Baltic gray seal females examined during 1973-2007, in relation to the levels of polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) in Baltic biota, using an estimated exposure index. Additionally, the proliferative activity in leiomyomas, occurrence of corpora lutea, and blubber concentrations of PCB and DDT were investigated in a subset of females. Leiomyomas were only found in females 22-41 years old, at a prevalence of 65%. No differences in blubber concentrations of PCB or DDT were detected between the subset of leiomyoma-bearing females and reference females, but the estimated exposure index indicated that the PCB level in Baltic biota might be related to the leiomyoma prevalence in Baltic gray seal females.
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| 5. |
- Danielsson, Bengt R., et al.
(author)
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Embryonic cardiac arrhythmia and generation of reactive oxygen species : common teratogenic mechanism for IKr blocking drugs
- 2007
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 24:1, s. 42-56
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Journal article (peer-reviewed)abstract
- In the adult organism, it is well established that hypoxia followed by reperfusion may be fatal and result in generation of reactive oxygen species (ROS) and subsequent tissue damage. There is also considerable evidence that temporary decrease or interruption in oxygen supply to the embryo and ROS generation during reperfusion result in tissue damage in embryonic tissues. A wide spectrum of different malformations by transient embryonic hypoxia could be produced, depending on the duration, extent, and timing of the hypoxic event. It is the contention of this paper that drugs that block the potassium channel IKr, either as an intended pharmacologic effect or as an unwanted side-effect, are potentially teratogenic by a common ROS related mechanism. Drugs blocking the IKr channel, such as almokalant, dofetilide, phenytoin, cisapride and astemizole, do all produce a similar pattern of hypoxia-related malformations. Mechanistic studies show that the malformations are preceded by embryonic cardiac arrhythmia and periods of hypoxia/reoxygenation in embryonic tissues. Pretreatment or simultaneous treatment with radical scavengers with capacity to capture ROS, markedly decrease the teratogenicity of different IKr blocking drugs. A second aim of this review is to demonstrate that the conventional design of teratology studies is not optimal to detect malformations caused by IKr blocking drugs. Repeated high doses result in high incidences of embryonic death due embryonic cardiac arrhythmia, thus masking their teratogenic potential. Instead, single dosing on specific days is proposed to be a better way to characterize the teratogenic potential of Ikr blocking drugs.
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| 6. |
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| 7. |
- Fernández, Estíbaliz L., et al.
(author)
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Expression of ZnT-1 (Slc30al) and MT-1 (Mt1) in the conceptus of cadmium treated mice
- 2007
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 24:3-4, s. 353-358
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Journal article (peer-reviewed)abstract
- There are indications that Cd-induced malformations in rodents are related to a disrupted flux of Zn to the developing embryo. The aim of the present study was to detect ZnT-1 (Slc30al) and MT (Mt1) protein in structures within the decidua, yolk sac and embryo of mice and to determine whether Cd affects ZnT-1 or MT-1 gene expression in these tissues. ZnT-1 was detected in the placental labyrinth, in the ventral part around the floor plate, in the inner cell layers of the rhombencephalon and in the ventral area of the otic vesicle. MT protein was detected in the yolk sac and in the Surface ectoderm of some embryonic areas, such as the pharyngeal arches. ZnT-1 and MT-1 transcripts were most abundant in the decidua and yolk sac, whereas the abundance of these genes was relatively low in the embryo. Cd exposure down-regulated ZnT-1 and up-regulated MT-1 gene expression in all structures investigated, indicating that maternal Cd exposure may alter Zn homeostasis in the conceptus.
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| 8. |
- Gäreskog, Mattias, et al.
(author)
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Maternal diabetes in vivo and high glucose concentration in vitro increases apoptosis in rat embryos
- 2007
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 23:1, s. 63-74
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Journal article (peer-reviewed)abstract
- Apoptosis may be involved in diabetes-induced embryonic dysmorphogenesis. We estimated the occurrence of apoptosis in embryos of a rat model for diabetic pregnancy. We found decreased Bcl-2, increased Bax and cleaved Caspase 3 proteins in embryos from diabetic rats. Moreover, we found increased activation of Caspase 3 in cells from embryos previously exposed to a diabetes-like environment (in vivo, in vitro) compared to cells from control embryos, which was normalized by supplementation of N-acetylcysteine or apoptosis inhibitor. We detected increased propidium iodide uptake in embryonic cells exposed to maternal diabetes, a finding confirmed by vital staining. Additionally, we found increased dysmorphogenesis in embryos exposed to a diabetic environment in vivo and in vitro. Exposure to a diabetic milieu during organogenesis increases apoptosis in embryonic cells and dysmorphogenesis in embryos. Enhanced apoptotic rate may have a role in diabetic embryopathy by inducing disturbed embryonic maturation, increased rates of resorptions and congenital malformations.
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| 9. |
- Johansson, Stefan, et al.
(author)
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Infection with Parvovirus B19 and Herpes viruses in early pregnancy and risk of second trimester miscarriage or very preterm birth
- 2008
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 26:3-4, s. 298-302
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Journal article (peer-reviewed)abstract
- We investigated whether infections with Parvovirus B19 and Herpes viruses in early pregnancy increase risks of second trimester miscarriage or delivery before 32 gestational weeks. Blood samples taken in early pregnancy were analyzed for Parvovirus B19 or Herpes viruses. Viremia was found in blood samples of 11 (4.7%) women with second trimester miscarriage and 10 (3.7%) women with very preterm birth, compared to 5 (1.7%) women who delivered at term, corresponding to adjusted odds ratios [95% CI] of 3.32 [0.93, 11.8] and 2.21 [0.71, 6.84], respectively. In stratified analyses, Parvovirus B19 viremia was associated with adjusted odds ratios of 3.76 [0.77, 18.3] for second trimester miscarriage and 2.66 [0.64, 11.1] for very preterm birth. Corresponding odds ratios for Human Herpes virus 6 viremia was 2.52 [0.33, 19.5] and 1.08 [0.14, 8.08], respectively. In conclusion, this study lends some support to the hypothesis that women with viremia in early pregnancy may face an increased risk of second trimester miscarriage or very preterm birth. Studies with larger sample sizes are needed.
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| 10. |
- Kultima, Kim, et al.
(author)
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Cadmium-induced gene expression changes in the mouse embryo, and the influence of pretreatment with zinc
- 2006
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 22:4, s. 636-646
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Journal article (peer-reviewed)abstract
- Cadmium (Cd) administered to female C57BL/6 mice on gestation day 8 induces a high incidence of anterior neural tube defects (exencephaly). This adverse effect can be attenuated by maternal pretreatment with zinc (Zn). In this study we used replicated microarray analysis and real-time PCR to investigate gene expression changes induced in the embryo 5 and 10h after maternal Cd exposure in the absence or presence of Zn pretreatment. We report nine genes with a transcriptional response induced by Cd, none of which was influenced by Zn pretreatment, and two genes induced only by combined matemal Cd exposure and Zn pretreatment. We discuss the results in relation to the possibility that Cd is largely excluded from the embryo, that the teratogenic effects of Cd may be secondary to toxicity in extraembryonic tissues, and that the primary protective role of Zn may not be to reverse Cd-induced transcription in the embryo.
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