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Andrey HöglundForskare

Om mig

I'm a postdoctoral researcher at Stockholm University with a PhD in Genetics. My primary research interest is to understand the transcriptional mechanisms and epigenetic landscapes that facilitate biological responses to adverse exposures. In my currect projects the adverse effects of the environmental pollutants PFOS and DBP are investigated

Publikationer

I urval från Stockholms universitets publikationsdatabas

  • Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates

    2024. Denise Strand (et al.). Cell Biology and Toxicology 40 (1)

    Artikel

    Many persistent organic pollutants (POPs) are suspected endocrine disruptors and it is important to investigate their effects at low concentrations relevant to human exposure. Here, the OECD test guideline #456 steroidogenesis assay was downscaled to a 96-well microplate format to screen 24 POPs for their effects on viability, and testosterone and estradiol synthesis using the human adrenocortical cell line H295R. The compounds (six polyfluoroalkyl substances, five organochlorine pesticides, ten polychlorinated biphenyls and three polybrominated diphenyl ethers) were tested at human-relevant levels (1 nM to 10 µM). Increased estradiol synthesis, above the OECD guideline threshold of 1.5-fold solvent control, was shown after exposure to 10 µM PCB-156 (153%) and PCB-180 (196%). Interestingly, the base hormone synthesis varied depending on the cell batch. An alternative data analysis using a linear mixed-effects model that include multiple independent experiments and considers batch-dependent variation was therefore applied. This approach revealed small but statistically significant effects on estradiol or testosterone synthesis for 17 compounds. Increased testosterone levels were demonstrated even at 1 nM for PCB-74 (18%), PCB-99 (29%), PCB-118 (16%), PCB-138 (19%), PCB-180 (22%), and PBDE-153 (21%). The MTT assay revealed significant effects on cell viability after exposure to 1 nM of perfluoroundecanoic acid (12%), 3 nM PBDE-153 (9%), and 10 µM of PCB-156 (6%). This shows that some POPs can interfere with endocrine signaling at concentrations found in human blood, highlighting the need for further investigation into the toxicological mechanisms of POPs and their mixtures at low concentrations relevant to human exposure.

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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. Andrey Höglund (et al.). PLOS Genetics 20 (3)

    Artikel

    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, 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.

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  • Automated Image-Based Fluorescence Screening of Mitochondrial Membrane Potential in Daphnia magna: An Advanced Ecotoxicological Testing Tool

    2024. Cedric Abele (et al.). Environmental Science and Technology 58 (36), 15926-15937

    Artikel

    This study demonstrated thestrengths ofinvivo molecular staining coupled with automated imaging analysis in Daphnia magna. Amultiwell plate protocol wasdeveloped toassess mitochondrial membrane potential using theJC-1 dye. The suitability offivecommon anesthetics wasinitially tested, and5% ethanol performed bestinterms ofanesthetic effects andhealthy recovery. The staining conditions were optimized to30min staining with 2 μM JC-1 forbest J-aggregate formation. The protocol wasvalidated with themodel compound carbonyl cyanide 3-chlorophenylhydrazone (CCCP) andused tomeasure theeffect offour environmental contaminants, 2,4-dinitrophenol, triclosan, n-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), and ibuprofen, onmitochondrial health. Test organisms were imaged using anautomated confocal microscope, and fluorescence intensities were automatically quantified. The effect concentrations forCCCP were lower byafactor of30compared with thetraditional OECD 202acute toxicity test.Mitochondrial effects were alsodetected atlower concentrations foralltested environmental contaminants compared totheOCED 202test.For 2,4-dinitrophenol, mitochondria effects were detectable after 2hexposure toenvironmentally relevant concentrations andpredicted organism death wasobserved after 24h.Thehigh sensitivity andtime efficiency ofthisnovel automated imaging method make ita valuable toolforadvancing ecotoxicological testing.

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  • Genomic and gene expression associations to morphology of a sexual ornament in the chicken

    2022. Vid Bakovic (et al.). G3 12 (9)

    Artikel

    How sexual selection affects the genome ultimately relies on the strength and type of selection, and the genetic architecture of the involved traits. While associating genotype with phenotype often utilizes standard trait morphology, trait representations in morphospace using geometric morphometric approaches receive less focus in this regard. Here, we identify genetic associations to a sexual ornament, the comb, in the chicken system (Gallus gallus). Our approach combined genome-wide genotype and gene expression data (>30k genes) with different aspects of comb morphology in an advanced intercross line (F8) generated by crossing a wild-type Red Junglefowl with a domestic breed of chicken (White Leghorn). In total, 10 quantitative trait loci were found associated to various aspects of comb shape and size, while 1,184 expression QTL were found associated to gene expression patterns, among which 98 had overlapping confidence intervals with those of quantitative trait loci. Our results highlight both known genomic regions confirming previous records of a large effect quantitative trait loci associated to comb size, and novel quantitative trait loci associated to comb shape. Genes were considered candidates affecting comb morphology if they were found within both confidence intervals of the underlying quantitative trait loci and eQTL. Overlaps between quantitative trait loci and genome-wide selective sweeps identified in a previous study revealed that only loci associated to comb size may be experiencing on-going selection under domestication. 

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