| 1. |
- Murto, Tiina, 1975-, et al.
(författare)
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Compliance to the recommended use of folic acid supplements for women in Sweden is higher among those under treatment for infertility than among fertile controls and is also related to socioeconomic status and lifestyle
- 2017
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Ingår i: Food & Nutrition Research. - : TAYLOR & FRANCIS LTD. - 1654-6628 .- 1654-661X. ; 61
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Tidskriftsartikel (refereegranskat)abstract
- Background: Folate has been discussed in relation to fertility among women, but studies on women under treatment for infertility are lacking.Objective: The objective of this study was to investigate folic acid supplement use and folate status among women under treatment for infertility (hereafter infertile) and fertile women also in regard to socioeconomic and lifestyle factors.Design: Lifestyle and dietary habits, and use of dietary supplements were assessed using a questionnaire. Blood samples were obtained for analysis of folate status. 24-hour recall interviews were also performed.Results: Highly educated, employed and infertile women were most prone to using folic acid supplements. The infertile women had a significantly better folate status than the fertile women. Folate status did not correlate with socioeconomic or lifestyle factors. The infertile women were physically more active, smoked less and were employed. Our questionnaire data had only fair agreement with the data from 24-hour recalls, but the folate status data was clearly correlated to our questionnaire results.Conclusions: Infertile women were most prone to using folic acid supplements and had better folate status than the controls. High educational and employment status were found to be key factors for high compliance to the recommended use folic acid supplements.
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| 2. |
- Murto, Tiina, 1975-
(författare)
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Folate, Hormones and Infertility : Different factors affecting IVF pregnancy outcome
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Various hormones have been studied as regards prediction of pregnancy outcome after infertility treatment, but no ideal candidate has been found. Folate and genetic variations in folate metabolism have also been associated with infertility, but it remains unclear how these factors affect IVF pregnancy outcome. It is known that infertility is associated with active folic acid supplement use, but the effect of socioeconomic and lifestyle factors on folic acid supplement use in infertile women has not been well investigated. The overall aim of this work was to obtain information on the prediction of live birth, and to study factors affecting the role of folate and folic acid intake in relation to IVF pregnancy outcome. Infertile women with various infertility diagnoses were studied. Healthy, fertile non-pregnant women were used as controls in three of the studies. Blood samples were taken for assay of eight different hormones, folate and homocysteine, and for genomic DNA extraction. A questionnaire was used to assess background data and use of folic acid supplements. Twenty-four-hour recall interviews were performed for validation of the questionnaire. The studied hormones were not good predictors of live birth. The best predictor was age of the women, together with ovulatory menstrual cycles, and thyroid-stimulating hormone and anti-Müllerian hormone (AMH) status. Well-educated women, high-status employed women, and married and infertile women used the most folic acid supplements. Infertile women had better folate status than fertile women. However, pregnancy outcome after infertility treatment was not dependent on folic acid intake, folate status, genetic variation of 5,10-methylenetetrahydrofolate reductase or socioeconomic status. In conclusion, AMH levels vary less than those of other hormones during the menstrual cycle, and AMH could be used as a predictive marker of live birth together with age and ovulation. Folate might play a minor role in IVF pregnancy outcome, but the importance of folate as regards other health perspectives should not be forgotten.
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| 3. |
- Murto, Tiina, et al.
(författare)
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Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility
- 2014
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Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 28:6, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- Folic acid supplements are commonly used by infertile women and lead to a positive folate status. However, the effect of folic acid supplements on pregnancy outcome in women with unexplained infertility has not been well investigated. This study evaluated folic acid supplement use and folate status in women with unexplained infertility in relation to pregnancy outcome. In addition, use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile, nonpregnant control women. Women with unexplained infertility used significantly more folic acid supplements and had higher median total folic acid intake from supplements compared with fertile control women (both P < 0.001). Women with unexplained infertility also had significantly higher median plasma folate and lower median plasma homocysteine concentrations than fertile women (both P < 0.001), but folic acid supplementation or folate status were not related to pregnancy outcome in women with unexplained infertility. In conclusion, folic acid supplementation or good folate status did not have a positive effect on pregnancy outcome following infertility treatment in women with unexplained infertility.
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| 4. |
- Murto, Tiina, 1975-, et al.
(författare)
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Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR) gene variations in relation to IVF pregnancy outcome
- 2014
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:1, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study folic acid intake, folate status and pregnancy outcome after infertility treatment in women with different infertility diagnoses in relation to methylenetetrahydrofolate reductase (MTHFR) 677C>T, 1298A>C and 1793G>A polymorphisms. Also the use of folic acid supplements, folate status and the frequency of different gene variations were studied in women undergoing infertility treatment and fertile women.DESIGN: Observational study.SETTING: University hospital.POPULATION: Women undergoing infertility treatment and healthy, fertile, non-pregnant women.METHODS: A questionnaire was used to assess general background data and use of dietary supplements. Blood samples were taken to determine plasma folate and homocysteine levels, and for genomic DNA extraction. A comparison of four studies was performed to assess pregnancy outcome in relation to MTHFR 677 TT vs. CC, and 1298 CC vs. AA polymorphisms.MAIN OUTCOME MEASURES: Folic acid supplement intake, and plasma folate, homocysteine and genomic assays.RESULTS: Women in the infertility group used significantly more folic acid supplements and had better folate status than fertile women, but pregnancy outcome after fertility treatment was not dependent on folic acid intake, folate status or MTHFR gene variations.CONCLUSION: High folic acid intakes and MTHFR gene variations seem not associated with helping women to achieve pregnancy during or after fertility treatment.
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| 5. |
- Murto, Tiina, 1975-, et al.
(författare)
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Socioeconomic and lifestyle factors in relation to folic acid supplement use in infertile and fertile Swedish women
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Socioeconomic and lifestyle factors are considered to be associated with folic acid supplement use and intake in the general population, but studies on infertile women are lacking. When investigating dietary supplement intake, the validity of the assessment of reported supplement use and actual intake is crucial. The objective of the study was to investigate socioeconomic, lifestyle and dietary factors in relation to folic acid supplement use and folate status in infertile and fertile women. In addition, a sub-analysis was performed to validate the used questionnaire. Methods: In this observational study, 340 infertile women and 188 fertile women were investigated. A questionnaire was used to assess lifestyle and dietary habits and use of dietary supplements. Blood samples were obtained for analyses of plasma folate and homocysteine levels. 24-hour recall interviews were performed to validate the questionnaire. Results: Folic acid supplement use was related to marital status, educational level and employment status. Infertile women had significantly higher mean folic acid daily intake and better folate status. However, folate status did not correlate with socioeconomic or lifestyle factors. The infertile women were physically more active, smoked less and had better employment status, but they were also more obese than fertile women. Socioeconomic and lifestyle factors were not related to in vitro fertilization outcome. Dietary data from the questionnaires showed good validity compared with the data from the 24-hour recall interviews, but data regarding folic acid supplement use showed only fair agreement between these methods. Conclusions: Highly educated, employed, married and infertile women were most prone to using folic acid supplements. Only a few socioeconomic and lifestyle factors differed between infertile and fertile women, and these were not related to folate status or IVF outcome. Methods other than a questionnaire are recommended when investigating folic acid supplement use.
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| 6. |
- Skoog, Tiina, et al.
(författare)
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Matrix metalloproteinase-21 expression is associated with keratinocyte differentiation and upregulated by retinoic acid in HaCaT cells
- 2009
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 129:1, s. 119-30
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Tidskriftsartikel (refereegranskat)abstract
- In the skin, expression of several matrix metalloproteinases (MMPs) occurs in response to tissue injury, tumorigenesis, angiogenesis, apoptosis, and inflammation. The recently cloned MMP-21 has been implicated in skin development and various epithelial cancers. In this study, we found that it is also expressed by differentiated keratinocytes (KCs) in various benign skin disorders, in which it was not associated with KC apoptosis or proliferation, and in organotypic cultures. Furthermore, MMP-21 was induced in keratinocytes in association with increased calcium and presence of the differentiation marker filaggrin. In stably transfected A431 and HEK293 cell lines, MMP-21 increased invasion of cells but did not associate with increased apoptosis, proliferation, or epithelial-to-mesenchymal transition. Of various agents tested in HaCaT cell cultures, only retinoic acid (10(-6) M) and staurosporine (2.5 x 10(-8) M) upregulated MMP-21 mRNA and protein expression, whereas tumor promoters, hormones, or dexamethasone were without effect. Our results suggest that MMP-21 may be an important protease in the terminal differentiation of keratinocytes.
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| 7. |
- Skoog, Tiina
(författare)
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Regulation of TNF-alpha : implications for health and disease
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine, which is implicated in some metabolic disorders and may play a role in the development of cardiovascular disease. When healthy 50-year-old men were studied, the plasma TNF-alpha concentration was associated with systolic and diastolic blood pressure, degree of alimentary lipaemia, plasma VLDL triglyceride and LDL cholesterol concentrations, peak LDL particle size and all measured cell adhesion molecules. Two indices of insulin resistance also correlated positively with TNF-alpha. The plasma TNF-alpha concentration was associated with common carotid IMT in univariate but not in multivariate analysis where soluble E-selectin and postprandial triglycerides were independent predictors of IMT. The regulation of TNF-alpha expression in man is indicated to be partly genetically determined. Therefore, a 1263 base pair section of the proximal promoter of the TNF-alpha gene was screened for common functional polymorphisms. A C to A substitution at position -863 was found to exhibit distinct differences between the alleles in the binding of monocytic and hepatic nuclear factors. The rare -863A-allele was associated with 31% lower basal transcriptional activity (p<0.05) in-CAT reporter gene studies in human HepG2 cells. Allele frequency for the rare A- allele was 17% amongst 254 apparently healthy men of Swedish origin, aged 35-50 years. In 156 men, carriers of the rare allele had significantly lower TNF-alpha serum levels (p<0.05). Further, the molecular mechanism underlying the allele-specific regulation of TNF-alpha gene expression under both basal and LPS-stimulated conditions was studied. Several transcription factors, in particular the NF-kappaB p50/p65 heterodimer, were shown to be involved in LPS-induced allele-specific regulation of TNF-alpha gene expression. Despite a strong LPS-dependent activation of the endogenous TNF-alpha gene expression, LPS did not activate the TNF-alpha promoter in transient transfections. Accordingly, it was hypothesized that the lack of LPS- mediated transcriptional activation in transient transfection assays could be explained by the missing chromatin structure, normally acting as a repressor of the transcriptional machinery. It was demonstrated with DNase I hypersensitivity assays that the chromatin structure is remodeled upon LPS stimulation and that the DNA-chromatin configuration is changed over time. The association of different TNF-alpha promoter polymorphisms with TNF-alpha secretion from human subcutaneous adipose tissue was studied in 24 non-obese (BMI<30) healthy control subjects and 59 obese subjects (BMI>30). The secretion rate of TNF-alpha was about 3 times greater in non-obese subjects homozygous for the -863C allele than in carriers of the A-allele (p<0.05). Of note, the levels of TNF-alpha did not differ between carriers and non-carriers of the A- allele in obese individuals. In conclusion, our results show that the plasma TNF-alpha concentration is associated with degree of early atherosclerosis and correlates with metabolic and cellular perturbations that are considered important for the progression of atherosclerosis. The common -863C/A polymorphism in the promoter region of the TNF-alpha gene is functional in vitro in monocytic and hepatic cells, and influences the serum TNF-alpha concentration in vivo in healthy middle-aged men and the secretion of TNF-alpha from adipose tissue from non-obese individuals ex vivo.
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| 8. |
- Wedenoja, Satu, et al.
(författare)
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Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia
- 2020
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 59
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses.Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth. We studied placental mRNA expression of 136 genes by sequencing and HLA-G and interferon alpha (IFNα) protein expression by immunohistochemistry.Findings: We found underrepresentation of males in preeclamptic births, especially those delivered preterm or small for gestational age. Balancing selection at HLA-G associated with the sex ratio, stillbirth, and preeclampsia. We observed downregulation of HLA-G, its receptors, and many other tolerogenic genes, and marked upregulation of IFNA1 in preeclamptic placentas.Interpretation: These findings indicate that an evolutionary trade-off between immune tolerance and protection against infections at the maternal-fetal interface promotes genetic diversity in fetal HLA-G, thereby affecting survival, preeclampsia, and sex ratio. We highlight IFNA1 as a potential mediator of preeclampsia and a target for therapeutic trials.
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