| 1. |
- Alavian-Ghavanini, Ali, et al.
(författare)
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Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA) exposure has been linked to neurodevelopmental disorders and to effects on epigenetic regulation, such as DNA methylation, at genes involved in brain function. High doses of BPA have been shown to change expression and regulation of one such gene, Grin2b, in mice. Yet, if such changes occur at relevant doses in animals and humans has not been addressed. We investigated if low-dose developmental BPA exposure affects DNA methylation and expression of Grin2b in brains of adult rats. Furthermore, we assessed associations between prenatal BPA exposure and Grin2b methylation in 7-year old children. We found that Grin2b mRNA expression was increased and DNA methylation decreased in female, but not in male rats. In humans, prenatal BPA exposure was associated with increased methylation levels in girls. Additionally, Iow APGAR scores, a predictor for increased risk for neurodevelopmental diseases, were associated with higher Grin2b methylation levels in girls. Thus, we could link developmental BPA exposure and Iow APGAR scores to changes in the epigenetic regulation of Grin2b, a gene important for neuronal function, in a sexual dimorphic fashion. Discrepancies in exact locations and directions of the DNA methylation change might reflect differences between species, analysed tissues, exposure level and/or timing.
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| 2. |
- Bornehag, Carl-Gustaf, 1957-, et al.
(författare)
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The SELMA study : a birth cohort study in Sweden following more than 2000 mother-child pairs
- 2012
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Ingår i: Paediatric and Perinatal Epidemiology. - Hoboken, USA : Wiley-Blackwell. - 0269-5022 .- 1365-3016. ; 26:5, s. 456-467
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper describes the background, aim and study design for the Swedish SELMA study that aimed to investigate the importance of early life exposure during pregnancy and infancy to environmental factors with a major focus on endocrine disrupting chemicals for multiple chronic diseases/disorders in offspring.Methods: The cohort was established by recruiting women in the 10th week of pregnancy. Blood and urine from the pregnant women and the child and air and dust from home environment from pregnancy and infancy period have been collected. Questionnaires were used to collect information on life styles, socio-economic status, living conditions, diet and medical history.Results: Of the 8394 reported pregnant women, 6658 were invited to participate in the study. Among the invited women, 2582 (39%) agreed to participate. Of the 4076 (61%) non-participants, 2091 women were invited to a non-respondent questionnaire in order to examine possible selection bias. We found a self-selection bias in the established cohort when compared with the non-participant group, e.g. participating families did smoke less (14% vs. 19%), had more frequent asthma and allergy symptoms in the family (58% vs. 38%), as well as higher education among the mothers (51% vs. 36%) and more often lived in single-family houses (67% vs. 60%).Conclusions: These findings indicate that the participating families do not fully represent the study population and thus, the exposure in this population. However, there is no obvious reason that this selection bias will have an impact on identification of environmental risk factors.
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| 3. |
- Bölling, Anette, et al.
(författare)
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Pulmonary phthalate exposure and asthma - is PPAR a plausible mechanistic link?
- 2013
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Ingår i: EXCLI Journal. - : Universität Mainz. - 1611-2156. ; 12, s. 733-759
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Tidskriftsartikel (refereegranskat)abstract
- Due to their extensive use as plasticisers in numerous consumer products, phthalates have become ubiquitous environmental contaminants. An increasing number of epidemiological studies suggest that exposure to phthalates may be associated with worsening or development of airway diseases. Peroxisome Proliferation Activated Receptors (PPAR)s, identified as important targets for phthalates in early studies in rodent liver, have been suggested as a possible mechanistic link. In this review we discuss the likelihood of an involvement of PPARs in asthma development and exacerbation due to pulmonary phthalate exposure. First, we go through the literature on indoor air levels of phthalates and pulmonary phthalate kinetics. These data are then used to estimate the pulmonary phthalate levels due to inhalation exposure. Secondly, the literature on phthalate-induced activation or modulation of PPARs is summarized. Based on these data, we discuss whether pulmonary phthalate exposure is likely to cause PPAR activation, and if this is a plausible mechanism for adverse effects of phthalates in the lung. It is concluded that the pulmonary concentrations of some phthalates may be sufficient to cause a direct activation of PPARs. Since PPARs mainly mediate antiinflammatory effects in the lungs, a direct activation is not a likely molecular mechanism for adverse effects of phthalates. However, possible modulatory effects of phthalates on PPARs deserve further investigation, including partial antagonist effects and/or cross talk with other signalling pathways. Moreover other mechanisms, including interactions between phthalates and other receptors, could also contribute to possible adverse pulmonary effects of phthalates.
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| 4. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 5. |
- Engh, Lisbet, 1954-
(författare)
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Skolsköterskans möjlighet att upptäcka och stödja barn som far illa eller riskerar att fara illa
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since children are a vulnerable group, the society has a special responsibility to protect them. The school nurse sees all pupils at school at regular health visits and thereby gains knowledge of their health and living conditions. The overall aim of the thesis was to develop empirical knowledge and understanding of the ability of the school nurse to detect and support children who are maltreated or at risk to be maltreated. The thesis is based on four studies. Study I was based on focus group interviews with school nurses. Data was analysed in accordance with Grounded Theory. Study II was a secondary analysis of study I and performed with Thematic Analysis. Studies III and IV were based on population data which was analysed by univariate and multivariate logistic regressions. The results showed that the school nurse has ability to detect children who are maltreated or at risk to be maltreated. However, also obstacles for detection were found such as lack of trust, avoidance, strong feelings and insufficient documentation. The obstacles were partly due to organisational shortcomings and dearth of resources affecting also internal and external collaboration. The school nurse strived for building trustful relations to pupils, to parents and to professionals. If the school nurse failed to report suspected child maltreatment to the child protection services it was because of worries that the reporting did not benefit the child. The school nurse avoided addressing child sexual abuse because of its particular sensitiveness, which affected the possibility to detect the abuse. Pupils in foster care were at higher risk of health problems, a more risky lifestyle, a lower degree of school attachment and lower school performance compared to pupils not in foster care. The results emphasize the potential of the school nurse to detect and support maltreated children through regular contacts with pupils, their confidence in the school nurse and trustful relations with other professionals.
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| 6. |
- Guo, Jing, et al.
(författare)
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Pulmonary toxicity and adjuvant effect of di-(2-exylhexyl) phthalate in ovalbumin-immunized BALB/c mice
- 2012
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Asthma is a complex pulmonary inflammatory disease, which is characterized by airway hyperresponsiveness, variable airflow obstruction and inflammation in the airways. The majority of asthma is allergic asthma, which is a disease caused by type I hypersensitivity mediated by IgE. Exposures to a number of environmental chemicals are suspected to lead to asthma, one such pollutant is di-(2-ethylheyl) phthalate (DEHP). DEHP is a manufactured chemical that is commonly added in plastic products to make them flexible. Epidemiological studies have revealed a positive association between DEHP exposure and asthma prevalence.METHODOLOGY/PRINCIPAL FINDINGS: The present study was aimed to determine the underlying role of DEHP exposure in airway reactivity, especially when combined with allergen exposure. The biomarkers include pulmonary histopathology, airway hyperresponsiveness (lung function), IgE, IL-4, IFN-γ and eosinophils. Healthy balb/c mice were randomly divided into eight exposure groups (n = 8 each): (1) saline control, (2) 30 µg/(kg•d) DEHP, (3) 300 µg/(kg•d) DEHP, (4) 3000 µg/(kg•d) DEHP, and (5) ovalbumin (OVA)-sensitized group, (6) OVA-combined with 30 µg/(kg•d) DEHP, (7) OVA-combined with 300 µg/(kg•d) DEHP, and (8) OVA-combined with 3000 µg/(kg•d) DEHP. Experimental tests were conducted after 52-day DEHP exposure and subsequently one week of challenge with aerosolized OVA. The principal findings include: (1) Strong postive associations exist between OVA-combined DEHP exposure and serum total IgE (T-IgE), as well as histological findings. These positive associations show a dose-dependent low dose sensitive effect of DEHP. (2) IL-4, eosinophil recruitment and lung function are also indicators for adjuvant effect of DEHP.CONCLUSIONS/SIGNIFICANCE: Our results suggest that except the significant changes of immunological and inflammatory biomarkers (T-IgE, IL-4, IFN-γ and eosinophils), the pulmonary histological (histopathological examination) and physiological (lung function) data also support that DEHP may promote and aggravate allergic asthma by adjuvant effect.
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| 7. |
- Rendel, Filip, et al.
(författare)
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Effects of Di-Isononyl Phthalate on Neuropeptide Y Expression in Differentiating Human Neuronal Cells
- 2017
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Blackwell Publishing. - 1742-7835 .- 1742-7843. ; 120:3, s. 218-323
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) is an abundant neuropeptide in the mammalian brain important for behavioural consequences of stress and energy metabolism. We have addressed possible effects of the phthalate DiNP on NPY expression in human SH‐SY5Y cells, a neuronal in vitro differentiation model. Pico‐ to nanomolar doses of DiNP and its metabolite MiNP resulted in decreased NPY mRNA and peptide expression in retinoid‐differentiated cells. Thus, dys‐regulated NPY may be an adverse outcome for exposure to low doses of DiNP in human beings.
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| 8. |
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| 9. |
- Shu, Huan, 1980-, et al.
(författare)
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PVC flooring at home and development of asthma among young children in Sweden, a 10-year follow-up
- 2014
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Ingår i: Indoor Air. - : Blackwell Publishing. - 0905-6947 .- 1600-0668. ; 24:3, s. 227-235
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of asthma and allergy has increased throughout the developed world over the past decades. During the same period of time, the use of industrial chemicals such as phthalates, commonly used as plasticizers in polyvinylchloride (PVC) flooring material, has increased. The aim of this study was to investigate whether PVC flooring in the home of children in the age of 1–5 years is associated with the development of asthma in 5‐ and 10‐year follow‐up investigations (n = 3228). Dampness in Buildings and Health Study (DBH Study) commenced in 2000 in Värmland, Sweden. The current analyses included subjects who answered all baseline and follow‐up questionnaires. Logistic regression analyses were applied to questionnaire results. Children who had PVC floorings in the bedroom at baseline were more likely to develop doctor‐diagnosed asthma during the following 10‐year period when compared with children living without. There were indications that PVC flooring in the parents' bedrooms was strongly associated with the new cases of doctor‐diagnosed asthma when compared with child′s bedroom. Our results suggest that PVC flooring exposure during pregnancy could be a critical period in the development of asthma in children at a later time; prenatal exposure and measurements of phthalate metabolites should be included in the future.
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| 10. |
- Shu, Huan, 1980-, et al.
(författare)
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PVC flooring at home and uptake of phthalates in pregnant women
- 2019
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Ingår i: Indoor Air. - : John Wiley & Sons. - 0905-6947 .- 1600-0668. ; 29:1, s. 43-54
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it is known that phthalates may migrate into the surrounding environment and then become a source for human uptake. The aim of the study was to investigate whether residential PVC flooring was related to the urinary levels of phthalate metabolites determined in pregnant women. The data were from the Swedish SELMA study where sampling was conducted during the time period 2007-2010. Spot urine samples from 1674 women at the end of the first trimester were analyzed for 14 metabolites from seven phthalates and one phthalate alternative. Data on flooring material in the kitchen and the parents' bedrooms as well as potential confounders were collected by postal questionnaires at the same time as the urine samples were taken. Multiple regression modeling by least square geometric mean and weighted quantile sum regression was applied to log-transformed and creatinine-adjusted phthalate metabolite concentrations adjusted for potential confounders from questionnaire data. This study has found significantly higher urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes with PVC flooring as compared to homes with other flooring materials
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