| 1. |
- Bolin, Marie, et al.
(författare)
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Angiopoietin-1/angiopoietin-2 ratio for prediction of preeclampsia
- 2009
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 22:8, s. 891-895
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A number of different biophysical and biochemical markers have been proposed as predictors of preeclampsia. Factors involved in the angiogenic balance are suggested as candidate markers. The purpose of this prospective, longitudinal cohort study was to determine whether a ratio between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) can be used to predict preeclampsia in a low-risk population. METHODS: A cohort of healthy pregnant women (n = 469) were enrolled at gestational weeks 8-12. Plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. By using commercially available enzyme-linked immunosorbent assay kits Ang-1 and Ang-2 were analyzed. RESULTS: The median Ang-1/Ang-2 ratio increased during pregnancy in all women, but the ratios were significantly lower at gestational weeks 25 and 28 in women who later developed preeclampsia than in normal pregnant women (1.49 compared to 2.19 and 2.12 compared to 3.54, P < 0.05 and P < 0.05). CONCLUSION: Our data indicate that in a low-risk population of women the Ang-1/Ang-2 ratio in plasma constitutes a possible biomarker for prediction of later onset of preeclampsia.
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| 2. |
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| 3. |
- Bourlev, Vladimir, et al.
(författare)
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The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions
- 2006
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Ingår i: Reproduction. - : Bioscientifica. - 1470-1626 .- 1476-3990 .- 1741-7899. ; 132:3, s. 501-509
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Tidskriftsartikel (refereegranskat)abstract
- Studies were performed to elucidate the possible relationship between microvessel density, proliferative activity and angiogenesis in eutopic endometrium from women with and without endometriosis and peritoneal endometriotic lesions. The question whether changes in these parameters in endometriotic lesions were reflected by the level of vascular endothelial growth factor-A (VEGF-A) in serum and peritonea fluid was also studied. Biopsy specimens of both eutopic endometrium and peritoneal endometriotic lesions from women with endometriosis (n=25) as well as eutopic endometrium from women without endometriosis (n=14) were analysed immunohistochemically regarding microvessel density, proliferative activity, and expression of VEGF-A and its receptors vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2) in stroma, glands and blood vessels. The VEGF-A concentration was measured in peritoneal fluid and serum. Secretory phase eutopic endometrium from women with endometriosis had significantly higher microvessel density, expression of VEGF-A in glandular epithelium and VEGFR-2 in endometrial blood vessels than those from women without endometriosis. Endometriotic lesions with high proliferative activity had a higher microvessel density and showed higher vascular expression of VEGFR-2 as well as being accompanied by higher levels of VEGF-A in peritoneal fluid and serum, compared with lesions with low proliferative activity. In conclusion, there seems to be a dysregulation of angiogenic activity in the eutopic endometrium of women with endometriosis and endometriotic lesions with high proliferative activity were accompanied by higher local angiogenic activity and higher levels of VEGF in serum and peritoneal fluid.
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| 4. |
- Bredhult, Carolina, et al.
(författare)
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Effects of chlorinated biphenyls and metabolites on human uterine myocyte proliferation
- 2007
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Ingår i: Human and Experimental Toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 26:10, s. 801-809
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Tidskriftsartikel (refereegranskat)abstract
- Uterine myometrial cells are responsive to sex steroids, which could make them susceptible to actions of endocrine disrupting environmental contaminants such as some PCBs. The aim of this investigation was to identify possible effects of some chlorinated biphenyls (CBs) and their metabolites on myometrial cell proliferation. Myometrial cells obtained from women in both phases of the menstrual cycle and from pregnant women were grown in vitro and exposed to CB 101, CB 118, 3'-MeSO2-CB 101, 4'-MeSO2-CB 101, 4-OH-CB 107, 17 beta-estradiol, progesterone, ethinylestradiol or levonorgestrel. The proliferative activity was studied by a BrdU assay. Myometrial cell cultures originating from pregnant women exhibited decreased proliferation in response to 3'-MeSO2-CB 101, 4'-MeSO2-CB 101 and 4-OH-CB 107. Estradiol, a combination of 1 nM 17 beta-estradiol and 10 nM progesterone, ethinylestradiol and levonorgestrel also reduced the proliferation of the myometrial cells, regardless of whether the cells were collected from either of the menstrual cycle phases or from pregnant women. To our knowledge this study is the first to demonstrate that some CBs affect the proliferative activity of human uterine myocytes.
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| 5. |
- Bredhult, Carolina, 1980-
(författare)
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Effects of some Endocrine Disruptors on Human and Grey Seal Uterine Cells
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The effects of environmental contaminants in humans and animals are of great concern. Some contaminants are endocrine disruptors that may interfere with the endogenous hormonal signalling and disturb, for example, reproductive organs and functions.Primary uterine myometrial cells originating from women and Baltic grey seals were exposed to some polychlorinated biphenyls (PCBs) and their metabolites. Even though human and Baltic grey seal myometrial cells responded differently to the tested PCBs, the results indicate that PCBs can influence myometrial cell proliferation in vitro.The prevalence of uterine leiomyomas was investigated among 257 Baltic grey seals. Leiomyomas were only present in females older than 22 years, at a prevalence of 65%. Proliferation in leiomyoma cells was detected in individuals lacking ovarian proliferation support, suggesting the presence of an exogenous stimulant. By taking into account temporal alterations in the contaminant burden of the seals, PCB exposure was found to be associated with leiomyoma prevalence. In conclusion, PCB exposure may be related to uterine leiomyoma development and proliferation in Baltic grey seals in vivo.Human endometrial endothelial cells (HEECs) were exposed to some endocrine disruptors, and the effects of the endocrine disruptors on cell proliferation and viability were studied. All evaluated endocrine disruptors decreased HEEC proliferation and most also decreased HEEC viability. Further studies revealed that the reduction in HEEC proliferation after exposure to o,p’-DDT was associated with differential expression of mRNA involved in proliferation, defence response, and lipid and cholesterol metabolism compared to untreated HEEC. In conclusion, these studies suggest that endocrine disruptors affect cultured cells from the female reproductive tract of humans and grey seals, and may have deleterious effects on proliferation, viability, and genes involved in defence response, and lipid or cholesterol metabolism.
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| 6. |
- Bredhult, Carolina, et al.
(författare)
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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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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 23:4, s. 550-559
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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.
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| 7. |
- Bredhult, Carolina, et al.
(författare)
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Gene expression analysis of human endometrial endothelial cells exposed to Bisphenol A
- 2009
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 28:1, s. 18-25
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Bredhult, Carolina, et al.
(författare)
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Gene expression analysis of human endometrial endothelial cells exposed to o,p'-DDT
- 2008
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Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 14:2, s. 97-106
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Tidskriftsartikel (refereegranskat)abstract
- The endocrine disrupting chemical o, p'-dichlorodiphenyltrichloroethane (DDT) can affect reproductive organs, tissues and cells in several species. Treatment of human endometrial endothelial cells (HEECs) with 50 mu M o, p'0- DDT decreased their proliferation compared with the control. Microarray analyses revealed that o, p'-DDT affected biological processes such as the cell cycle, cell division, defence response and lipid and steroid metabolism, in cellular components such as the plasma membrane and chromosomes, with molecular functions involved in signalling, receptor and cytokine activity, confirming the results of the proliferation assay. Expression of five of the most differentially expressed genes identified in the microarray analysis was verified by real- time quantitative reverse transcription polymerase chain reaction 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 o, p'- DDT. The present study supports our previous findings of decreased proliferation and increased cell death in response to o, p'- DDT and may offer important clues to the mechanisms of action of o, p'-DDT.
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| 9. |
- Bredhult, Carolina, et al.
(författare)
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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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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 25:2, s. 247-255
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Tidskriftsartikel (refereegranskat)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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| 10. |
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