Biology subjects

Stoger, R.

Publications and source records attributed to Stoger, R..

5 recordsLinked to original sources

bioRxiv2020

Childhood location correlates with epigenetic age and methylation stability in British-Bangladeshi migrants

BackgroundMigration from one environment to another often causes marked changes in developmental conditions. Here we compare epigenetic ageing and stability of the epigenetic maintenance system among British-Bangladeshi women who grew up in Bangladesh (adult migrants), where there are higher pathogen loads and poorer health care, to second-generation Bangladeshis who grew up in the UK. In our previous studies of these migrants, those who spent their childhoods in Bangladesh also had lower levels of reproductive hormones and a shorter reproductive lifespan compared to those who grew up in the UK, suggesting life history trade-offs during development. In the present study, we hypothesised that women who grew up in Bangladesh would have i) an older epigenetic/biological age compared to the women with a childhood in the UK and ii) that differences in the pace of epigenetic ageing might also be reflected by altered stability of DNA methylation marks. ResultsIllumina EPIC array methylation data from buccal tissue was used to establish epigenetic age estimates from 15 adult migrants and 11 second-generation migrants, aged 18-35 years. Using residuals from linear regression of DNA methylation-based biological age (DNAm age) on the chronological age, the results showed significant differences (p=0.016) in epigenetic age estimates: women whose childhood was in Bangladesh are on average 6.02 ({+/-} 2.34) years older, than those who grew up in London. We further investigated the efficiency of the epigenetic maintenance system which purportedly is reflected by epigenetic clocks. Methylation states of CpGs at the LHCGR/LHR locus, which contributes to Horvaths multi tissue epigenetic clock were evaluated. Based on the Ratio of Concordance Preference (RCP) approach that uses double-stranded methylation data, we find that maintenance of epigenetic information is more stable in women who grew up in Bangladesh. ConclusionsThe work supports earlier findings that adverse childhood environments lead to phenotypic life history trade-offs. The data indicate that childhood environments can induce subtle changes to the epigenetic maintenance system that are detectable long after exposure occurred. The implication of such a finding warrants further investigation as it implies that a less flexible epigenetic memory system established early in life could reduce the capacity to respond to different environmental conditions in adult life.

genetics↗

bioRxiv2020

Early-life environment programs reproductive strategies through epigenetic regulation of SRD5A1

Reproductive function and duration of the reproductive life span are phenotypically plastic and programmed in response to the early-life environment. Such adaptive responses are described and rationalized in life history theory in the context of resource availability, but the molecular mechanisms responsible have remained enigmatic. In this study, we hypothesized that epigenetic modifications underlie adaptive reproductive strategies, and found distinct methylation patterns in buccal DNA of Bangladeshi women who grew up in Bangladesh or the UK. The later pubertal onset and lower ovarian reserve associated with Bangladeshi childhood was seen to correlate with more numerous childhood infections, so we adopted a mouse model of pre-pubertal colitis to mimic these conditions. These mice have a similarly-altered reproductive phenotype, which enabled us to determine its mechanistic basis. Several genes encoding proteins with known functions in follicle recruitment were differentially expressed in the mice ovaries, and were also differentially methylated in the womens buccal DNA. One of these, SRD5A1 which encodes the steroidogenic enzyme 5 reductase-1, was down-regulated in the mice ovaries and hyper methylated at the same putative transcriptional enhancer as in the womens DNA; the levels of methylation correlating with gene expression levels. Srd5a1 expression was down-regulated also in the hypothalamus where 5 reductase-1 catalyzes production of neurosteroids that regulate gonadotropin releasing hormone (GnRH). Chemical inhibition of this enzyme affected both GnRH synthesis and release, and resulted in delayed pubertal onset in vivo. The activity of 5 reductase-1 in hypothalamus and ovary and the sensitivity of SRD5A1 to epigenetic regulation attest to its role in directing long-term physiological strategies in response to environmental conditions. In the reproductive axis, this includes timing of pubertal onset, adult reproductive function and duration of the reproductive lifespan.

developmental biology↗

bioRxiv2020

Feeding recombinant Royalactin: Measures of improved lifespan and mitochondrial function in Caenorhabditis elegans

Ageing, the decline of biological functions over time, is inherent to eukaryotes. Female honeybees attain a long-lived queen phenotype upon continuous consumption of royal jelly, whereas restricted supply of this nutritional substance promotes the development of worker bees, which are short-lived. An abundant protein found within royal jelly is major royal jelly protein 1 (MRJP1), also known as Royalactin. Health- and lifespan promoting effects have been attributed to Royalactin in species from diverse animal taxa, suggesting it acts on phylogenetically conserved physiological processes. Here, we explore the effects of feeding the nematode Caenorhabditis elegans with Escherichia coli that express a recombinant form of Royalactin (RArec). We confirm that consumption of RArec increases body size, improves locomotion and extends lifespan. We discover a link between Royalactin and mitochondria, organelles which play a key part in the ageing process: both spare respiratory capacity and morphology indicate improved mitochondrial function in RArec fed C. elegans. These results demonstrate the feasibility of using recombinant Royalactin to gain further insight into processes of healthy ageing in many species. RArec production allows insight into potential beneficial effects across species.

physiology↗

bioRxiv2019

Thiamethoxam exposure in honey bees deregulates short ORF gene expression in the brain and compromises the immune response

Maximizing crop yields relies on the use of agrochemicals to control insect pests. One of the most widely used classes of insecticides are neonicotinoids that interfere with signalling of the neurotransmitter acetylcholine, but these can also disrupt crop-pollination services provided by bees. Here, we analysed whether chronic low dose long-term exposure to the neonicotinoid thiamethoxam alters gene expression and alternative splicing in brains of Africanized honey bees, Apis mellifera, as adaptation to altered neuronal signalling. We find differentially regulated genes that show concentration-dependent responses to thiamethoxam, but no changes in alternative splicing. Most differentially expressed genes have no annotated function but encode short Open Reading Frames (sORFs), a characteristic feature of anti-microbial peptides. As this suggested that immune responses may be compromised by thiamethoxam exposure, we tested the impact of thiamethoxam on bee immunity by injecting bacteria. We show that intrinsically sub-lethal thiamethoxam exposure makes bees more vulnerable to normally non-pathogenic bacteria. Our findings imply a synergistic mechanism for the observed bee population declines that concern agriculturists, conservation ecologists and the public.

pharmacology and toxicology↗

bioRxiv2019

Acute Thiamethoxam exposure in Apis mellifera : Absence of both stress-induced changes in mRNA splicing and synergistic effects of common fungicide and herbicide

Securing food supply for a growing population is one of the current major challenges and heavily relies on the use of agrochemicals to maximize crop yield. Neonicotinoids are globally one of the most widely used insecticides. It is increasingly recognized, that neonicotinoids have a negative impact on non-target organisms, including important pollinators such as the European honey bee Apis mellifera. Toxicity of neonicotinoids may be enhanced through simultaneous exposure with additional pesticides, which could help explain, in part, the global decline of honey bee colonies. Here we examined whether exposure effects of the neonicotinoid Thiamethoxam are enhanced by the commonly used fungicide Carbendazim and the herbicide Glyphosate. For the first time, we also analysed alternative splicing changes upon pesticide exposure in the honey bee. In particular, we examined transcripts of three genes: i) the stress sensor gene X box binding protein-1 (Xbp1), ii) the Down Syndrome Cell Adhesion Molecule (Dscam) gene and iii) the embryonic lethal/abnormal visual system (elav) gene, both important genes for neuronal function. Our results indicate that neonicotinoid toxicity applied at sub-lethal doses is not enhanced by Carbendazim nor Glyphosate. Likewise, toxicity of these compounds did not impact on the complex process of spliceosomal-directed joining of exons and non-spliceosomal intron excision in the analysed mRNAs.

pharmacology and toxicology↗