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Effects of egg enrichment with glucocorticoid hormone, antagonist and receptor messenger in the modulation of gene expression in zebrafish (Danio rerio) embryos

ABSTRACT: Several studies have shown the presence of large reservoirs of maternally contributed liposoluble hormones in the yolk of mature teleost oocytes, such as steroid, thyroid and retinoid hormones, as found in other oviparous vertebrates. This supports the idea that maternal hormones could play a major role in regulating developmental processes post-fertilization. The aims of this study were: A) to verify whether a cortisol treatment of zebrafish eggs affects the growth rate of the progenies as compared to controls in F1-F4 treated generations (ontogenetic programming). It was to be established whether: 1) this is due to a short-term effect of maternal cortisol, directly producing an initial growth retard that is not compensated later on in lifetime (short-term epigenetic effect); or 2) this is due to a long-term priming of growth rate by maternal cortisol that persists later on in lifetime (long-term epigenetic effect); B) to verify whether the ontogenetic programming is inheritable, being transmitted also to the untreated F4 generation. It was to be established whether the programmed genes are developmental and/or growth genes that are inhibited, or genes encoding hormones of the corticoid stress axis (hypothalamo-hypophyso-interrenal axis) that are amplified, or both gene clusters.

ORGANISM(S): Danio rerio

PROVIDER: GSE52398 | GEO | 2016/01/01

SECONDARY ACCESSION(S): PRJNA227778

REPOSITORIES: GEO

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Project description:We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol result in fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies in which we extended the duration of cortisol infusion (1mg/kg/d) to term, we found a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol and associated maternal hyperglycemia. To investigate the effects on the heart, transcriptomic analyses were performed on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the effects of 10 days of maternal cortisol infusion (130d-cortisol vs 130d control), ~25 days (term at ~140d-cortisol vs 140d control), normal maturation (140d-control vs 130d control) were performed. In all analyses gene ontology (GO) terms related to immune function and cytokine actions were significantly over-represented. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly over-represented, consistent with our previous findings. We found significantly differentially regulated genes in the term fetuses (ie after ~25 days of cortisol) in pathways consistent with altered metabolism in the heart, particularly in mitochondria, associated with responses to hypoxia and to nutrient. Analysis of mitochondrial number by quantitative real-time PCR confirmed a significant decrease. These pathways were different from those modeled following the normal increase in cortisol in late gestation which contributes to normal maturation of the heart, and thus may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by diabetes, CushingM-bM-^@M-^Ys disease and chronic stress. 2 cohorts of singleton sheep fetuses at 129-131d gestation or 139-144d gestation (approximately term) were used. The first cohort received maternal cortisol infusion of 1mg/kg/day or vehicle for 10 days until approximately day 130 of gestation (n=6/group), the second cohort received the same dose of cortisol for approximately 25 days until near term (n=7, cortisol; n=7ewes, n=8 fetuses due to one set of twins, control)

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Effects of egg enrichment with glucocorticoid hormone, antagonist and receptor messenger in the modulation of gene expression in zebrafish (Danio rerio) embryos

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