| 1. |
- Álvarez-Rodríguez, Manuel, et al.
(author)
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Transgenerational and Epigenetic Impacts of Environmental Exposures in Male Reproduction
- 2018. - 2
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In: Encyclopedia of Reproduction (Second Edition). - : Elsevier. - 9780128151457 ; , s. 634-641
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Book chapter (other academic/artistic)abstract
- The vertebrate zygote results from the merging of two highly specialized gamete cells, namely the oocyte and the spermatozoon, and has the outstanding potential of creating all cells in the future developing embryo. For this to occur, however, the genome of the gametes is mostly striped of “epigenetic marks,” or proteins and methyl groups attached to the DNA. Epigenetic marks in the genome constitute the so-called epigenome and have the potential for long term regulation of gene expression. Environmental insults during the highly susceptible and delicate period of germ cell development could, by altering the epigenome of spermatozoa, affect the phenotype of future generations (transgenerational epigenetic inheritance). A brief review of how epigenetics can act transgenerationally through the male germline is hereby presented.
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| 2. |
- Fallet, Manon, 1992-, et al.
(author)
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Present and future challenges for the investigation of transgenerational epigenetic inheritance
- 2023
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In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 172
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Research review (peer-reviewed)abstract
- Epigenetic pathways are essential in different biological processes and in phenotype-environment interactions in response to different stressors and they can induce phenotypic plasticity. They encompass several processes that are mitotically and, in some cases, meiotically heritable, so they can be transferred to subsequent generations via the germline. Transgenerational Epigenetic Inheritance (TEI) describes the phenomenon that phenotypic traits, such as changes in fertility, metabolic function, or behavior, induced by environmental factors (e.g., parental care, pathogens, pollutants, climate change), can be transferred to offspring generations via epigenetic mecha-nisms. Investigations on TEI contribute to deciphering the role of epigenetic mechanisms in adaptation, adver-sity, and evolution. However, molecular mechanisms underlying the transmission of epigenetic changes between generations, and the downstream chain of events leading to persistent phenotypic changes, remain unclear. Therefore, inter-, (transmission of information between parental and offspring generation via direct exposure) and transgenerational (transmission of information through several generations with disappearance of the triggering factor) consequences of epigenetic modifications remain major issues in the field of modern biology.In this article, we review and describe the major gaps and issues still encountered in the TEI field: the general challenges faced in epigenetic research; deciphering the key epigenetic mechanisms in inheritance processes; identifying the relevant drivers for TEI and implement a collaborative and multi-disciplinary approach to study TEI. Finally, we provide suggestions on how to overcome these challenges and ultimately be able to identify the specific contribution of epigenetics in transgenerational inheritance and use the correct tools for environmental science investigation and biomarkers identification.
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| 3. |
- Guerrero-Bosagna, Carlos, 1975-
(author)
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DNA Methylation Research Methods
- 2014
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In: Materials and Methods. - : Labome. - 2329-5139.
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Other publication (peer-reviewed)
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| 4. |
- Guerrero-Bosagna, Carlos, 1975-, et al.
(author)
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Environmentally induced epigenetic transgenerational inheritance of male infertility
- 2014
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In: Current Opinion in Genetics and Development. - : Elsevier. - 0959-437X .- 1879-0380. ; 26, s. 79-88
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Journal article (peer-reviewed)abstract
- Decreasing male fertility has been observed for the past fifty years. Examples of affected reproductive parameters include decreases in sperm count and sperm quality and increases in testicular cancer, cryptorchidism and hypospadias. Exposures to environmental toxicants during fetal development and early postnatal life have been shown to promote infertility. Environmental exposures inducing epigenetic changes related to male infertility range from life style, occupational exposures, environmental toxicants and nutrition. Exposures during fetal gonadal sex determination have been shown to alter the epigenetic programming of the germline that then can transmit this altered epigenetic information to subsequent generations in the absence of any exposures. This environmentally induced epigenetic transgenerational inheritance of disease will be a component of the etiology of male infertility.
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| 5. |
- Guerrero-Bosagna, Carlos, 1975-
(author)
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Epigenetics, evolution and the survival of the non-unfit
- 2017
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In: The Biochemist. - : Biochemical Society. - 0954-982X .- 1740-1194. ; 39:5, s. 8-11
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Journal article (other academic/artistic)abstract
- The transition that occurred in vertebrates moving from water to land was a major step in the evolution of terrestrial animals. This is an evolutionary step that has always fascinated scientists and the general public. The land-to-water vertebrate transition happened around the Devonian period and involved structural changes such as the transition from fin to limb, a reduction of the gill arch, loss of the mid-fin and a reduction in the number of scales, among others. I will use this interesting example to depict how the same evolutionary process can be seen through two different lenses. One view, which is the most widespread way of seeing evolution, is the 'survival of the fittest'. The other is intentionally stated in the title as the double negative 'survival of the non-unfit'. Only semantic differences? Not in my view.
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| 6. |
- Guerrero-Bosagna, Carlos, 1975-, et al.
(author)
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Globalization, climate change, and transgenerational epigenetic inheritance: will our descendants be at risk?
- 2015
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In: Clinical Epigenetics. - : BioMed Central. - 1868-7083 .- 1868-7075. ; 7:8
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Journal article (peer-reviewed)abstract
- Transgenerational epigenetic inheritance has gained increased attention due to the possibility that exposure to environmental contaminants induce diseases that propagate across generations through epigenomic alterations in gametes. In laboratory animals,exposure to environmental toxicants such as fungicides, pesticides, or plastic compounds has been shown to produce abnormal reproductive or metabolic phenotypes that are transgenerationally transmitted. Human exposures to environmental toxicants have increased due to industrialization and globalization, as well as the incidence of diseases shown to be transgenerationally transmitted in animal models. This new knowledge poses an urgent call to study transgenerational consequences of current human exposures to environmental toxicants.
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| 7. |
- Guerrero-Bosagna, Carlos, 1975-, et al.
(author)
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Identification of genomic features in environmentally induced epigenetic transgenerational inherited sperm epimutations
- 2014
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:6, s. e100194-
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Journal article (peer-reviewed)abstract
- A variety of environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. The process involves exposure of a gestating female and the developing fetus to environmental factors that promote permanent alterations in the epigenetic programming of the germline. The molecular aspects of the phenomenon involve epigenetic modifications (epimutations) in the germline (e. g. sperm) that are transmitted to subsequent generations. The current study integrates previously described experimental epigenomic transgenerational data and web-based bioinformatic analyses to identify genomic features associated with these transgenerationally transmitted epimutations. A previously identified genomic feature associated with these epimutations is a low CpG density (<12/100bp). The current observations suggest the transgenerational differential DNA methylation regions (DMR) in sperm contain unique consensus DNA sequence motifs, zinc finger motifs and G-quadruplex sequences. Interaction of molecular factors with these sequences could alter chromatin structure and accessibility of proteins with DNA methyltransferases to alter de novo DNA methylation patterns. G-quadruplex regions can promote the opening of the chromatin that may influence the action of DNA methyltransferases, or factors interacting with them, for the establishment of epigenetic marks. Zinc finger binding factors can also promote this chromatin remodeling and influence the expression of non-coding RNA. The current study identified genomic features associated with sperm epimutations that may explain in part how these sites become susceptible for transgenerational programming.
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| 8. |
- Guerrero-Bosagna, Carlos, 1975-
(author)
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Transgenerational epigenetic inheritance in birds
- 2018
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In: Environmental Epigenetics. - Oxford, United Kingdom : Oxford University Press. - 2058-5888. ; 4:2
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Research review (peer-reviewed)abstract
- While it has been shown that epigenetics accounts for a portion of the variability of complex traits linked to interactions with the environment, the real contribution of epigenetics to phenotypic variation remains to be assessed. In recent years, a growing number of studies have revealed that epigenetic modifications can be transmitted across generations in several animal species. Numerous studies have demonstrated inter- or multi-generational effects of changing environment in birds, but very few studies have been published showing epigenetic transgenerational inheritance in these species. In this review, we mention work conducted in parent-to-offspring transmission analyses in bird species, with a focus on the impact of early stressors on behaviour. We then present recent advances in transgenerational epigenetics in birds, which involve germline linked non-Mendelian inheritance, underline the advantages and drawbacks of working on birds in this field and comment on future directions of transgenerational studies in bird species.
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| 9. |
- Höglund, Andrey, 1985-, et al.
(author)
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The methylation landscape and its role in domestication and gene regulation in the chicken
- 2020
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In: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 4, s. 1713-1724
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Journal article (peer-reviewed)abstract
- Domestication is one of the strongest examples of artificial selection and has produced some of the most extreme within-species phenotypic variation known. In the case of the chicken, it has been hypothesized that DNA methylation may play a mechanistic role in the domestication response. By inter-crossing wild-derived red junglefowl with domestic chickens, we mapped quantitative trait loci for hypothalamic methylation (methQTL), gene expression (eQTL) and behaviour. We find large, stable methylation differences, with 6,179 cis and 2,973 trans methQTL identified. Over 46% of the trans effects were genotypically controlled by five loci, mainly associated with increased methylation in the junglefowl genotype. In a third of eQTL, we find that there is a correlation between gene expression and methylation, while statistical causality analysis reveals multiple instances where methylation is driving gene expression, as well as the reverse. We also show that methylation is correlated with some aspects of behavioural variation in the inter-cross. In conclusion, our data suggest a role for methylation in the regulation of gene expression underlying the domesticated phenotype of the chicken.
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| 10. |
- Höglund, Andrey, 1985-, et al.
(author)
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The regulation of methylation on the Z chromosome and the identification of multiple novel Male Hyper-Methylated regions in the chicken
- 2024
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In: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 20:3
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Journal article (peer-reviewed)abstract
- DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. To investigate how variation in DNA methylation is regulated on the Z chromosome we utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals. The relatively large numbers of individuals allowed us to identify additional genomic MHM regions on the Z chromosome that were significantly differentially methylated between the sexes. These regions appear to down-regulate local gene expression in males, but not remove it entirely (unlike the lncRNAs identified in the initial MHM regions). These MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes. In addition, trans effect hotspots were also identified that were based on the autosomes but affected the Z, and also that were based on the Z chromosome but that affected autosomal DNA methylation regulation. In addition, quantitative trait loci (QTL) that regulate variation in methylation on the Z chromosome, and those loci that regulate methylation on the autosomes that derive from the Z chromosome were mapped. Trans-effect hotspots were also identified that were based on the autosomes but affected the Z, and also one that was based on the Z chromosome but that affected both autosomal and sex chromosome DNA methylation regulation. We show that both cis and trans loci that originate from the Z chromosome never exhibit an interaction with sex, whereas trans loci originating from the autosomes but affecting the Z chromosome always display such an interaction. Our results highlight how additional MHM regions are actually present on the Z chromosome, and they appear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Z chromosome to the autosomes. DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. We utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals, to investigate the role that methylation plays in regulating gene expression on the Z chromosome. Our results highlight how additional MHM regions are actually present on the Z chromosome, and they appear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Z chromosome to the autosomes. In addition, these MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes.
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| 11. |
- Jacobs, MN, et al.
(author)
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Marked for Life: Epigenetic Effects of Endocrine Disrupting Chemicals
- 2017
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In: ANNUAL REVIEW OF ENVIRONMENT AND RESOURCES, VOL 42. - : Annual Reviews. - 1543-5938 .- 1545-2050. - 9780824323424 ; 42, s. 105-160
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Research review (other academic/artistic)abstract
- The presence of human-made chemical contaminants in the environment has increased rapidly during the past 70 years. Harmful effects of such contaminants were first reported in the late 1950s in wildlife and later in humans. These effects are predominantly induced by endocrine disrupting chemicals (EDCs), chemicals that mimic the actions of endogenous hormones and leave marks at several levels of organization in organisms, from physiological outcomes (phenotypes) to molecular alterations, including epigenetic modifications. Epigenetic mechanisms play pivotal roles in the developmental processes that contribute to determining adult phenotypes, through so-called epigenetic programming. While there is increasing evidence that EDC exposure during sensitive periods of development can perturb epigenetic programming, it is unclear whether these changes are truly predictive of adverse outcomes. Understanding the mechanistic links between EDC-induced epigenetic changes and phenotypic endpoints will be critical for providing improved regulatory tools to better protect the environment and human health from exposure to EDCs.
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| 12. |
- Lees, John, 1986-, et al.
(author)
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The mitoepigenome responds to stress, suggesting novel mito-nuclear interactions in vertebrates
- 2023
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In: BMC Genomics. - : BMC. - 1471-2164. ; 24
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Journal article (peer-reviewed)abstract
- The mitochondria are central in the cellular response to changing environmental conditions resulting from disease states, environmental exposures or normal physiological processes. Although the influences of environmental stressors upon the nuclear epigenome are well characterized, the existence and role of the mitochondrial epigenome remains contentious. Here, by quantifying the mitochondrial epigenomic response of pineal gland cells to circadian stress, we confirm the presence of extensive cytosine methylation within the mitochondrial genome. Furthermore, we identify distinct epigenetically plastic regions (mtDMRs) which vary in cytosinic methylation, primarily in a non CpG context, in response to stress and in a sex-specific manner. Motifs enriched in mtDMRs contain recognition sites for nuclear-derived DNA-binding factors (ATF4, HNF4A) important in the cellular metabolic stress response, which we found to be conserved across diverse vertebrate taxa. Together, these findings suggest a new layer of mito-nuclear interaction in which the nuclear metabolic stress response could alter mitochondrial transcriptional dynamics through the binding of nuclear-derived transcription factors in a methylation-dependent context.
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| 13. |
- Ludvigsson, Johnny, 1943-, et al.
(author)
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Toxic metals in cord blood and later development of Type 1 diabetes.
- 2019
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In: Pediatric dimensions. - 2397-950X. ; 4:2
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Journal article (peer-reviewed)abstract
- The incidence of type 1 diabetes (T1D) has increased explained by changes in environment or lifestyle. In modern society dissemination of heavy metals has increased. As the autoimmune process usually starts already, we hypothesized that exposure to toxic metals during fetal life might contribute to development of T1D in children. We analysed arsenic (AS), aluminium (Al), cadmium (Cd), lithium (Li), mercury (Hg), lead (Pb), in cord blood of 20 children who later developed T1D (probands), and in 40 age-and sex-matched controls. Analysis of heavy metals in cord blood was performed by ALS Scandinavia AB (Luleå, Sweden) using the 'ultrasensitive inductively coupled plasma sector field mass spectrometry method' (ICP-SFMS) after acid digestion with HNO3. Most children had no increased concentrations of the metals in cord blood. However, children who later developed T1D had more often increased concentrations (above limit of detection; LOD) of aluminium (p = 0.006) in cord blood than the non-diabetic controls, and also more often mercury and arsenic (n.s). Our conclusion is that exposure to toxic metals during pregnancy might be one among several contributing environmental factors to the disease process if confirmed in other birth cohort trials.
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| 14. |
- Rezaei, Shiva, et al.
(author)
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GBS-MeDIP : A protocol for parallel identification of genetic and epigenetic variation in the same reduced fraction of genomes across individuals
- 2022
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In: STAR protocols. - : Cell Press. - 2666-1667. ; 3:1
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Journal article (peer-reviewed)abstract
- The GBS-MeDIP protocol combines two previously described techniques, Geno-type-by-Sequencing (GBS) and Methylated-DNA- Immunoprecipitation (MeDIP). Our method allows for parallel and cost-efficient interrogation of genetic and methylomic variants in the DNA of many reduced genomes, taking advantage of the barcoding of DNA samples performed in the GBS and the subsequent creation of DNA pools, then used as an input for the MeDIP. The GBS-MeDIP is particularly suitable to identify genetic and methylomic biomarkers when resources for whole genome interrogation are lacking.
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| 15. |
- Rezaei, Shiva, et al.
(author)
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GBS-MeDIP: A protocol for parallel identification of genetic and epigenetic variation in the same reduced fraction of genomes across individuals
- 2022
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In: STAR Protocols. - : Cell Press. - 2666-1667. ; 3:1
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Journal article (peer-reviewed)abstract
- Summary:The GBS-MeDIP protocol combines two previously described techniques, Genotype-by-Sequencing (GBS) and Methylated-DNA-Immunoprecipitation (MeDIP). Our method allows for parallel and cost-efficient interrogation of genetic and methylomic variants in the DNA of many reduced genomes, taking advantage of the barcoding of DNA samples performed in the GBS and the subsequent creation of DNA pools, then used as an input for the MeDIP. The GBS-MeDIP is particularly suitable to identify genetic and methylomic biomarkers when resources for whole genome interrogation are lacking.
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| 16. |
- Rodriguez, Emiliano A. Videla, et al.
(author)
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Practical application of a Bayesian network approach to poultry epigenetics and stress
- 2022
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In: BMC Bioinformatics. - : BioMed Central. - 1471-2105. ; 23:1
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Journal article (peer-reviewed)abstract
- Background Relationships among genetic or epigenetic features can be explored by learning probabilistic networks and unravelling the dependencies among a set of given genetic/epigenetic features. Bayesian networks (BNs) consist of nodes that represent the variables and arcs that represent the probabilistic relationships between the variables. However, practical guidance on how to make choices among the wide array of possibilities in Bayesian network analysis is limited. Our study aimed to apply a BN approach, while clearly laying out our analysis choices as an example for future researchers, in order to provide further insights into the relationships among epigenetic features and a stressful condition in chickens (Gallus gallus). Results Chickens raised under control conditions (n = 22) and chickens exposed to a social isolation protocol (n = 24) were used to identify differentially methylated regions (DMRs). A total of 60 DMRs were selected by a threshold, after bioinformatic pre-processing and analysis. The treatment was included as a binary variable (control = 0; stress = 1). Thereafter, a BN approach was applied: initially, a pre-filtering test was used for identifying pairs of features that must not be included in the process of learning the structure of the network; then, the average probability values for each arc of being part of the network were calculated; and finally, the arcs that were part of the consensus network were selected. The structure of the BN consisted of 47 out of 61 features (60 DMRs and the stressful condition), displaying 43 functional relationships. The stress condition was connected to two DMRs, one of them playing a role in tight and adhesive intracellular junctions in organs such as ovary, intestine, and brain. Conclusions We clearly explain our steps in making each analysis choice, from discrete BN models to final generation of a consensus network from multiple model averaging searches. The epigenetic BN unravelled functional relationships among the DMRs, as well as epigenetic features in close association with the stressful condition the chickens were exposed to. The DMRs interacting with the stress condition could be further explored in future studies as possible biomarkers of stress in poultry species.
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| 17. |
- Skinner, Michael K., et al.
(author)
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Epigenetics and the Evolution of Darwin's Finches
- 2014
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In: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 6:8, s. 1972-1989
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Journal article (peer-reviewed)abstract
- The prevailing theory for the molecular basis of evolution involves genetic mutations that ultimately generate the heritable phenotypic variation on which natural selection acts. However, epigenetic transgenerational inheritance of phenotypic variation may also play an important role in evolutionary change. A growing number of studies have demonstrated the presence of epigenetic inheritance in a variety of different organisms that can persist for hundreds of generations. The possibility that epigenetic changes can accumulate over longer periods of evolutionary time has seldom been tested empirically. This study was designed to compare epigenetic changes among several closely related species of Darwin's finches, a well-known example of adaptive radiation. Erythrocyte DNA was obtained from five species of sympatric Darwin's finches that vary in phylogenetic relatedness. Genome-wide alterations in genetic mutations using copy number variation (CNV) were compared with epigenetic alterations associated with differential DNA methylation regions (epimutations). Epimutations were more common than genetic CNV mutations among the five species; furthermore, the number of epimutations increased monotonically with phylogenetic distance. Interestingly, the number of genetic CNV mutations did not consistently increase with phylogenetic distance. The number, chromosomal locations, regional clustering, and lack of overlap of epimutations and genetic mutations suggest that epigenetic changes are distinct and that they correlate with the evolutionary history of Darwin's finches. The potential functional significance of the epimutations was explored by comparing their locations on the genome to the location of evolutionarily important genes and cellular pathways in birds. Specific epimutations were associated with genes related to the bone morphogenic protein, toll receptor, and melanogenesis signaling pathways. Species-specific epimutations were significantly overrepresented in these pathways. As environmental factors are known to result in heritable changes in the epigenome, it is possible that epigenetic changes contribute to the molecular basis of the evolution of Darwin's finches.
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| 18. |
- Skinner, Michael K., et al.
(author)
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Role of CpG deserts in the epigenetic transgenerational inheritance of differential DNA methylation regions
- 2014
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In: BMC Genomics. - : BioMed Central. - 1471-2164. ; 15:692
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Journal article (peer-reviewed)abstract
- BACKGROUND:Previously a variety of environmental toxicants were found to promote the epigenetic transgenerational inheritance of disease through differential DNA methylation regions (DMRs), termed epimutations, present in sperm. The transgenerational epimutations in sperm and somatic cells identified in a number of previous studies were further investigated.RESULTS:The epimutations from six different environmental exposures were found to be predominantly exposure specific with negligible overlap. The current report describes a major genomic feature of all the unique epimutations identified (535) as a very low (<10 CpG/100 bp) CpG density in sperm and somatic cells associated with transgenerational disease. The genomic locations of these epimutations were found to contain DMRs with small clusters of CpG within a general region of very low density CpG. The potential role of these epimutations on gene expression is suggested to be important.CONCLUSIONS:Observations suggest a potential regulatory role for lower density CpG regions termed "CpG deserts". The potential evolutionary origins of these regions is also discussed.
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| 19. |
- Tatemoto, Patricia, et al.
(author)
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An enriched maternal environment and stereotypies of sows differentially affect the neuro-epigenome of brain regions related to emotionality in their piglets
- 2023
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In: Epigenetics. - : Taylor & Francis. - 1559-2294 .- 1559-2308. ; 18:1
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Journal article (peer-reviewed)abstract
- Epigenetic mechanisms are important modulators of neurodevelopmental outcomes in the offspring of animals challenged during pregnancy. Pregnant sows living in a confined environment are challenged with stress and lack of stimulation which may result in the expression of stereotypies (repetitive behaviours without an apparent function). Little attention has been devoted to the postnatal effects of maternal stereotypies in the offspring. We investigated how the environment and stereotypies of pregnant sows affected the neuro-epigenome of their piglets. We focused on the amygdala, frontal cortex, and hippocampus, brain regions related to emotionality, learning, memory, and stress response. Differentially methylated regions (DMRs) were investigated in these brain regions of male piglets born from sows kept in an enriched vs a barren environment. Within the latter group of piglets, we compared the brain methylomes of piglets born from sows expressing stereotypies vs sows not expressing stereotypies. DMRs emerged in each comparison. While the epigenome of the hippocampus and frontal cortex of piglets is mainly affected by the maternal environment, the epigenome of the amygdala is mainly affected by maternal stereotypies. The molecular pathways and mechanisms triggered in the brains of piglets by maternal environment or stereotypies are different, which is reflected on the differential gene function associated to the DMRs found in each piglets' brain region . The present study is the first to investigate the neuro-epigenomic effects of maternal enrichment in pigs' offspring and the first to investigate the neuro-epigenomic effects of maternal stereotypies in the offspring of a mammal.
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| 20. |
- Wegmann, Bertil, 1978-, et al.
(author)
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Identification of potentially relevant metals for the etiology of autism by using a Bayesian multivariate approach for partially censored values
- 2023
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In: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Heavy metals are known to be able to cross the placental and blood brain barriers to affect critical neurodevelopmental processes in the fetus. We measured metal levels (Al, Cd, Hg, Li, Pb and Zn) in the cord blood of newborns and in the serum of the same children at 5 years of age, and compared between individuals with or without (controls) autism spectrum disorder (ASD) diagnosis. The samples were from a biobank associated with the All Babies in Southeast Sweden (ABIS) registry. We proposed a Bayesian multivariate log-normal model for partially censored values to identify potentially relevant metals for the etiology of ASD. Our results in cord blood suggest prenatal Al levels could be indicative of later ASD incidence, which could also be related to an increased possibility of a high, potentially toxic, exposure to Al and Li during pregnancy. In addition, a larger possibility of a high, potentially beneficial, exposure to Zn could occur during pregnancy in controls. Finally, we found decisive evidence for an average increase of Hg in 5-year-old ASD children compared to only weak evidence for controls. This is concordant with previous research showing an impaired ability for eliminating Hg in the ASD group.
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