Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish

Glucocorticoids (GCs) in utero influence embryonic development with consequent programmed effects on adult physiology and pathophysiology and altered susceptibility to cardiovascular disease. However, in viviparous species, studies of these processes are compromised by secondary maternal influences. The zebrafish, being fertilised externally, avoids this problem and has been used here to investigate the effects of transient alterations in GC activity during early development. Embryonic fish were treated either with dexamethasone (a synthetic GC), an antisense GC receptor (GR) morpholino (GR Mo), or hypoxia for the first 120h post fertilisation (hpf); responses were measured during embryonic treatment or later, post treatment, in adults. All treatments reduced cortisol levels in embryonic fish to similar levels. However, morpholino- and hypoxia-treated embryos showed delayed physical development (slower hatching and straightening of head–trunk angle, shorter body length), less locomotor activity, reduced tactile responses and anxiogenic activity. In contrast, dexamethasone-treated embryos showed advanced development and thigmotaxis but no change in locomotor activity or tactile responses. Gene expression changes were consistent with increased (dexamethasone) and decreased (hypoxia, GR Mo) GC activity. In adults, stressed cortisol values were increased with dexamethasone and decreased by GR Mo and hypoxia pre-treatments. Other responses were similarly differentially affected. In three separate tests of behaviour, dexamethasone-programmed fish appeared ‘bolder’ than matched controls, whereas Mo and hypoxia pre-treated fish were unaffected or more reserved. Similarly, the dexamethasone group but not the Mo or hypoxia groups were heavier, longer and had a greater girth than controls. Hyperglycaemia and expression of GC responsive gene (pepck) were also increased in the dexamethasone group. We conclude that GC activity controls many aspects of early-life growth and development in the zebrafish and that, like other species, manipulating GC status pharmacologically, physiologically or genetically in early life leads to programmable metabolic and behavioural traits in adulthood.

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Adaptive response to a future life challenge: consequences of early-life environmental complexity in dual-purpose chicks

Journal of Animal Science ◽

10.1093/jas/skaa348 ◽

2020 ◽

Vol 98 (11) ◽

Author(s):

Chao Yan ◽

Kate Hartcher ◽

Wen Liu ◽

Jinlong Xiao ◽

Hai Xiang ◽

...

Keyword(s):

Gene Expression ◽

Gut Microbiota ◽

Early Life ◽

Plasma Corticosterone ◽

Adaptive Plasticity ◽

Environmental Complexity ◽

Dual Purpose ◽

Stress Related Genes ◽

Life Challenge ◽

Environmental Challenge

Abstract Conditions in early life play profound and long-lasting effects on the welfare and adaptability to stress of chickens. This study aimed to explore the hypothesis that the provision of environmental complexity in early life improves birds’ adaptive plasticity and ability to cope with a challenge later in life. It also tried to investigate the effect of the gut-brain axis by measuring behavior, stress hormone, gene expression, and gut microbiota. One-day-old chicks were split into 3 groups: (1) a barren environment (without enrichment items) group (BG, n = 40), (2) a litter materials group (LG, n = 40), and (3) a perches with litter materials group (PLG, n = 40). Then, enrichment items were removed and simulated as an environmental challenge at 31 to 53 d of age. Birds were subjected to a predator test at 42 d of age. In the environmental challenge, when compared with LG, PLG birds were characterized by decreased fearfulness, lower plasma corticosterone, improved gut microbial functions, lower relative mRNA expression of GR, and elevated mRNA expressions of stress-related genes CRH, BDNF, and NR2A in the hypothalamus (all P < 0.05). Unexpectedly, the opposite was true for the LG birds when compared with the BG (P < 0.05). Decreased plasma corticosterone and fearfulness were accompanied by altered hypothalamic gene mRNA expressions of BDNF, NR2A, GR, and CRH through the HPA axis in response to altered gut microbial compositions and functions. The findings suggest that gut microbiota may integrate fearfulness, plasma corticosterone, and gene expression in the hypothalamus to provide an insight into the gut-brain axis in chicks. In conclusion, having access to both perches and litter materials in early life allowed birds to cope better with a future challenge. Birds in perches and litter materials environment may have optimal development and adaptive plasticity through the gut-brain axis.

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Pentraxin 3: A Novel Biomarker for Inflammatory Cardiovascular Disease

International Journal of Vascular Medicine ◽

10.1155/2012/657025 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 18

Author(s):

Kenji Inoue ◽

Tatsuhiko Kodama ◽

Hiroyuki Daida

Keyword(s):

Gene Expression ◽

Cardiovascular Disease ◽

Pentraxin 3 ◽

Human Endothelial Cells ◽

C Reactive Protein ◽

Physiological Concentration ◽

Reactive Protein ◽

Atherosclerotic Lesions ◽

Human Genes

Numerous studies have recently examined the role of pentraxin 3 (PTX3) in clinical situations. The pentraxin family includes C-reactive protein (CRP); however, unlike CRP, PTX3 is expressed predominantly in atherosclerotic lesions that involve macrophages, neutrophils, dendritic cells, or smooth muscle cells. Interestingly, PTX3 gene expression in human endothelial cells is suppressed to a greater extent by pitavastatin than the expression of 6,000 other human genes that have been examined, suggesting that PTX3 may be a novel biomarker for inflammatory cardiovascular disease. The expression and involvement of PTX3 in cardiovascular diseases are discussed in this paper, along with the characteristics of PTX3 that make it a suitable biomarker; namely, that the physiological concentration is known and it is independent of other risk factors. The results discussed in this paper suggest that further investigations into the potential novel use of PTX3 as a biomarker for inflammatory cardiovascular disease should be undertaken.

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Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety

Developmental Neuroscience ◽

10.1159/000374108 ◽

2015 ◽

Vol 37 (3) ◽

pp. 203-214 ◽

Cited By ~ 14

Author(s):

Joshua L. Cohen ◽

Matthew E. Glover ◽

Phyllis C. Pugh ◽

Andrew D. Fant ◽

Rebecca K. Simmons ◽

...

Keyword(s):

Gene Expression ◽

Psychological Health ◽

Early Life ◽

Developmental Trajectory ◽

Emotional Behavior ◽

Developmental Gene ◽

Developmental Gene Expression ◽

Maternal Style ◽

Anxiety Depression ◽

Cross Fostering

The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations.

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DNA methylation and gene expression integration in cardiovascular disease

Clinical Epigenetics ◽

10.1186/s13148-021-01064-y ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Guillermo Palou-Márquez ◽

Isaac Subirana ◽

Lara Nonell ◽

Alba Fernández-Sanlés ◽

Roberto Elosua

Keyword(s):

Gene Expression ◽

Cardiovascular Disease ◽

Dna Methylation ◽

Cardiovascular Diseases ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Risk Function ◽

Predictive Biomarkers ◽

Independent Study ◽

Cell Type

Abstract Background The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event. Results Four independent latent factors (9, 19, 21—only in women—and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination. Conclusions Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.

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Factors affecting thyroid volume in adolescent students attending a rural middle school in East Hangzhou, China

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0422 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Qiaoyong Liu ◽

Yiqian Jiang ◽

Lijun Shen ◽

Jiming Zhu

Keyword(s):

Middle School ◽

Middle School Students ◽

Growth And Development ◽

Univariate Analysis ◽

Thyroid Volume ◽

Physical Development ◽

School Students ◽

Spearman's Rho ◽

Spearman’S Rho ◽

Rural Middle School

AbstractObjectiveTo investigate the thyroid volume (Tvol) and to explore factors that affects it among 12 to 15-year-olds attending a rural middle school in east Hangzhou, China.MethodsA cross-sectional survey of middle school students attending a rural middle school in east Hangzhou, China was conducted. Height, weight and other physical development related indicators in middle school students were measured. The thyroid size was measured using ultrasound, and the thyroid volume calculated.ResultsThe median (P25, P75) of the thyroid volume in 596 middle school students from a rural middle school in east Hangzhou, China was 6.69 (5.66, 7.98) mL. Our study enrolled 305 male students (51.2%) and 291 female students (48.8%). The height, weight and thyroid volume of middle school students increased with age. Univariate analysis revealed that height, weight, body mass index (BMI) and body surface area (BSA) were positive correlated with thyroid volume (p<0.01).The correlation between BSA and thyroid volume was significant (Spearman’s rho=0.473, p<0.01). Multiple linear regression analysis revealed that BSA was positive and significantly correlated with the thyroid volume (p<0.05). Regression equation was Y=−2.532 + 6.186×BSA.ConclusionThe thyroid volume is not only affected by age, but it is also affected by growth and development. Goiter cannot only be assessed based on age, gender and thyroid volume. However, this study established that BSA not only presented the strongest correlation with thyroid volume (Spearman’s rho=0.473), but also had a strong correlation with physical development, taking into account the growth and development of middle school students, and showed greater stability. Therefore, we recommend inclusion of BSA as a reference standard in the measurement of the thyroid volume.

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Protective effects of a unique combination of nutritionally active ingredients on risk factors and gene expression associated with atherosclerosis in C57BL/6J mice fed a high fat diet

Food & Function ◽

10.1039/d0fo02867c ◽

2021 ◽

Author(s):

Joe W. E. Moss ◽

Jessica O Williams ◽

Wijdan Al-Ahmadi ◽

Victoria O'Morain ◽

Yee-Hung Chan ◽

...

Keyword(s):

Gene Expression ◽

Risk Factors ◽

Cardiovascular Disease ◽

High Fat Diet ◽

Inflammatory Disorder ◽

Protective Effects ◽

Unique Combination ◽

Omega 3 ◽

High Fat ◽

Food Ingredients

Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease, is responsible for one in three global deaths. Consumption of active food ingredients such as omega-3...

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Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease

Journal of Human Genetics ◽

10.1038/s10038-020-00895-6 ◽

2021 ◽

Author(s):

Andrew A. Crawford ◽

◽

Sean Bankier ◽

Elisabeth Altmaier ◽

Catriona L. K. Barnes ◽

...

Keyword(s):

Gene Expression ◽

Cardiovascular Disease ◽

Genetic Variants ◽

Plasma Cortisol ◽

Statistical Power ◽

Mendelian Randomisation ◽

Eqtl Analysis ◽

Causative Role ◽

Peripheral Tissues ◽

Corticosteroid Binding Globulin

AbstractThe stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06–0.59) and myocardial infarction (0.21, 95% CI 0.00–0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.

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Transcriptome Analysis of Differentially Expressed mRNA Related to Pigeon Muscle Development

Animals ◽

10.3390/ani11082311 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2311

Author(s):

Hao Ding ◽

Yueyue Lin ◽

Tao Zhang ◽

Lan Chen ◽

Genxi Zhang ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Differentially Expressed Genes ◽

Growth And Development ◽

Muscle Development ◽

Expression Patterns ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Growth Stages ◽

Gene Expression And Regulation

The mechanisms behind the gene expression and regulation that modulate the development and growth of pigeon skeletal muscle remain largely unknown. In this study, we performed gene expression analysis on skeletal muscle samples at different developmental and growth stages using RNA sequencing (RNA−Seq). The differentially expressed genes (DEGs) were identified using edgeR software. Weighted gene co−expression network analysis (WGCNA) was used to identify the gene modules related to the growth and development of pigeon skeletal muscle based on DEGs. A total of 11,311 DEGs were identified. WGCNA aggregated 11,311 DEGs into 12 modules. Black and brown modules were significantly correlated with the 1st and 10th day of skeletal muscle growth, while turquoise and cyan modules were significantly correlated with the 8th and 13th days of skeletal muscle embryonic development. Four mRNA−mRNA regulatory networks corresponding to the four significant modules were constructed and visualised using Cytoscape software. Twenty candidate mRNAs were identified based on their connectivity degrees in the networks, including Abca8b, TCONS−00004461, VWF, OGDH, TGIF1, DKK3, Gfpt1 and RFC5, etc. A KEGG pathway enrichment analysis showed that many pathways were related to the growth and development of pigeon skeletal muscle, including PI3K/AKT/mTOR, AMPK, FAK, and thyroid hormone pathways. Five differentially expressed genes (LAST2, MYPN, DKK3, B4GALT6 and OGDH) in the network were selected, and their expression patterns were quantified by qRT−PCR. The results were consistent with our sequencing results. These findings could enhance our understanding of the gene expression and regulation in the development and growth of pigeon muscle.

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Social environment influences the relationship between genotype and gene expression in wild baboons

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0345 ◽

2013 ◽

Vol 368 (1618) ◽

pp. 20120345 ◽

Cited By ~ 19

Author(s):

Daniel E. Runcie ◽

Ralph T. Wiedmann ◽

Elizabeth A. Archie ◽

Jeanne Altmann ◽

Gregory A. Wray ◽

...

Keyword(s):

Gene Expression ◽

Individual Differences ◽

Social Environment ◽

Group Size ◽

Early Life ◽

Social Connectedness ◽

Dominance Rank ◽

Social Stressors ◽

The Social ◽

Wild Baboons

Variation in the social environment can have profound effects on survival and reproduction in wild social mammals. However, we know little about the degree to which these effects are influenced by genetic differences among individuals, and conversely, the degree to which social environmental variation mediates genetic reaction norms. To better understand these relationships, we investigated the potential for dominance rank, social connectedness and group size to modify the effects of genetic variation on gene expression in the wild baboons of the Amboseli basin. We found evidence for a number of gene–environment interactions (GEIs) associated with variation in the social environment, encompassing social environments experienced in adulthood as well as persistent effects of early life social environment. Social connectedness, maternal dominance rank and group size all interacted with genotype to influence gene expression in at least one sex, and either in early life or in adulthood. These results suggest that social and behavioural variation, akin to other factors such as age and sex, can impact the genotype–phenotype relationship. We conclude that GEIs mediated by the social environment are important in the evolution and maintenance of individual differences in wild social mammals, including individual differences in responses to social stressors.

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