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- Lizunkova, Polina
(author)
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Impact of epidemiologically identified mixtures of endocrine disrupting chemicals on metabolic programming
- 2023
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Doctoral thesis (other academic/artistic)abstract
- We are ubiquitously exposed to a plethora of endocrine-disrupting chemicals (EDCs), i.e. substances that alter the function(s) of the endocrine system. While ample evidence show individual EDC's influence on developmental processes resulting in adverse health outcomes, less is known about the effects of human-relevant EDC mixtures exposure. Additionally, there is a lack of appropriate methodology to assess the hazard and risk of complex mixtures.This doctoral project aimed to examine the effects of two EDC mixtures and to compare individual components to its mixture, on the developing metabolic system. And to investigate additivity approach for predicting effects of complex mixtures. Studied EDC mixtures (G and G1) were previously identified using Swedish Environmental Longitudinal Mother and Child Asthma and Allergy (SELMA) study data, based on their association with lower birth weight. In this thesis, these mixtures, and mixture G1’s components, were tested for effects on adipogenesis and underlying epigenetic and transcriptional changes in human mesenchymal stem cells (hMSCs) and on metabolic rate in zebrafish larvae.In hMSCs, both mixtures induced adipogenesis at concentrations corresponding to SELMA cohort measured levels. Mixture G induced early transcriptional changes of over 1000 genes in a dose-dependent manner. These genes significantly overlapped with glucocorticoid-regulated genes and were involved in early osteogenesis. Mixture G1 induced significant DNA methylation changes at 713 positions and in six genomic regions in genes whose expression or methylation was previously associated with obesity or MSC differentiation. In zebrafish larvae, mixture G1 increased oxygen consumption rate. Compared to mixture G1, none of its individual components showed equally large effects on adipogenesis or metabolic rate. However, mixture G1 effect on both endpoints could be adequately predicted by the additivity model using experimental data from its constituents.In conclusion, this doctoral project showed that mixtures corresponding to human real-life exposures, in terms of proportions and concentrations, can induce molecular, cellular, and whole-organism changes relevant to developmental metabolic programming, which could underlie adverse outcomes later in life. The results emphasise that mixtures matter and should be accounted for in regulatory risk assessments, and provide support for additivity models as a pragmatic approach to mixture risk assessment.
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| 2. |
- Engh, Lisbet, 1954-
(author)
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Skolsköterskans möjlighet att upptäcka och stödja barn som far illa eller riskerar att fara illa
- 2018
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Doctoral thesis (other academic/artistic)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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| 3. |
- Larsson, Malin, 1979-
(author)
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Indoor Environmental Factors and Chronic Diseases in Swedish Pre-School Children : Risk factors and methodological issues investigated in a longitudinal study on airway diseases and autism spectrum disorder
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Asthma and allergies have increased considerably during the past 40-50 years. Along with this increase, a heightened awareness regarding different neuro-developmental disorders such as autism spectrum disorder has occurred and it has been proposed that such disorders are also on the increase. It has been suggested that environmental factors, especially in the indoor environments, may be associated with the increase in these disorder, especially among children, who spend more than 90% of their time indoors. The aim of this thesis has been to investigate certain environmental factors in homes and their impact on children’s health, in terms of asthma, rhinitis, eczema as well as autism spectrum disorders, and to identify certain methodological difficulties in epidemiological investigations. We found that the mean incidence rate per year for doctor diagnosed asthma was in the range of 0.6-2.4% and for incidence of rhinitis 1.1-3.7%. The incidence rate of eczema ever was 2.7%. These results showed that when using a cohort established after birth the estimated incidence rates are strongly dependent of how the baseline population’s health and how the studied health outcome at follow up is defined. Our results showed that the associations between parental reported moisture problems in the home and asthma in children that were revealed in cross-sectional analyses decreased or disappeared when longitudinal data were used on the same data set. Our results therefore indicate that associations between parental reported moisture problems and asthma from cross-sectional questionnaire studies should be interpreted with caution due to the risk for reporting bias. Our results show that children who were living in homes with PVC-flooring in the bedroom in early childhood were more likely to develop asthma during the following 5-year period when compared with children living in homes without such flooring material. A similar association could be seen for children with autism spectrum disorder, where PVC-flooring in early childhood was associated with more reports of autism spectrum disorder five years later. These results indicate that building materials including suspected endocrine disrupting chemicals such as phthalates might be of importance for the development of these chronic diseases. Further studies are needed to explore the early life exposure and the mechanisms and contribution of phthalates for the development of chronic diseases.
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| 4. |
- Shu, Huan, 1980-
(author)
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Phthalates : On the issue of sources, human uptake, time trends and health effects
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Human health depends on a well-functioning endocrine system to regulate hormone release for normal bodily functions. Endocrine disrupting chemicals (EDCs) constitutes a group of chemicals, included in many commonly used products, (e.g., PVC flooring), with properties proven or suspected to interact with the natural hormone system in humans and animals. EDCs are manmade compounds (there are also natural compounds with such properties) that can bind to cell receptors and mimic or block the functions of natural hormones potentially resulting in adverse human health effects.One type of widely concerning EDC is phthalates. Since phthalates create weak chemical bonds when they are added into different products, they readily leach into the surrounding environment. Phthalate metabolites can therefore be frequently measured in human biological samples. Major public health concerns regarding EDCs over the past three decades have focused on phthalates. According to the World Health Organization, EDCs are suspected to be associated with altered reproductive function in males and females, increased incidence of breast cancer, abnormal growth patterns and neurodevelopmental delays in children, as well as changes in immune function.The thesis shows that PVC flooring in the home is a source for human uptake of phthalates, that replacement of phthalates in soft PVC products have an impact on human uptake of these chemicals, and that exposure for phthalates in early life increase the risk for airway disorders in children.As we have shown, ongoing regulations on phthalates is of importance for human uptake. Ultimately, individuals can make small changes in their consumer product choices that can lead to changes in uptake of chemicals with endocrine disrupting properties. Philosophically, we all have a responsibility to protect future generations from dangerous chemicals.
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| 5. |
- Svensson, Katherine
(author)
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Early life environmental exposures and children's growth : A longitudinal study evaluating prenatal exposure for endocrine disrupting chemicals and nutrition in relation to children's growth up to seven years of age
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Endocrine disrupting chemicals (EDCs) have the potential to disrupt the endocrine system in humans and animals with importance for health and development. Additionally, optimal nutrition during pregnancy is critical for fetal growth and pregnancy outcomes. However, further knowledge on the importance of EDC mixtures and nutrition, on birthweight and growth during childhood is needed. The overall aim of this thesis was to evaluate the associations between prenatal exposure to EDC mixtures and nutrition respectively, with birthweight, growth and body composition in early- and mid-childhood, and to determine if these associations differed by sex. Data from mother-child pairs in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study was analyzed, including 26 EDCs in prenatal urine and serum samples, children’s anthropometric and body composition measures up to seven years of age, and sociodemographic data from questionnaires and registers.Results suggest that higher prenatal exposure to EDC mixtures were associated with lower birthweight, and slower weight gain in early childhood, including a later peak growth velocity among girls. At 5.5 and 7 years of age, EDC mixtures were associated with lower BMI, less odds of overweight and less body fat among girls, but more body fat among boys at 7 years of age. Chemicals of concern in the mixtures were e.g., phthalates, bisphenols, perfluorinated alkyl substances (PFASs) and pesticides. Finally, maternal nutrition during pregnancy, i.e., better adherence to nutritional guidelines, was associated with more body fat for boys but less body fat for girls.In conclusion, prenatal exposure to both EDC mixtures and nutrition suggests to have an influence on birthweight, and children´s growth. Several of the found associations also differed by sex.
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