Preimplantation embryo ketone body exposure exerts sex-specific effects on mouse fetal and placental transcriptomes
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ABSTRACT:
PROVIDER: PRJNA900606 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22263900.fastq.gz | Fastqsanger.gz | |||
| SRR22263901.fastq.gz | Fastqsanger.gz | |||
| SRR22263902.fastq.gz | Fastqsanger.gz | |||
| SRR22263903.fastq.gz | Fastqsanger.gz | |||
| SRR22263904.fastq.gz | Fastqsanger.gz |
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Project description:Ketogenic diet consumption elevates circulating levels of the ketones β-hydroxybutyrate (βOHB) and acetoacetate (AcAc). In vitro ketone exposure perturbs preimplantation mouse embryo viability and female-specific fetal development post-transfer. Here we assessed whether transient exposure of preimplantation embryos to ketones impacts post-implantation fetal and placental gene expression. Blastocysts cultured in vitro with or without 2 mmol/L βOHB alone (‘βOHB’) or combined with 0.8 mmol/L AcAc (‘Keto’) underwent embryo transfer. Transcriptional profiles of sexed E14.5 placentae, liver, and brain were examined via RNA-Seq and DAVID functional analysis, revealing a sexually dimorphic transcriptomic response. βOHB and Keto exposure both downregulated genes related to oxidative phosphorylation specifically in female liver. βOHB downregulated female placental steroid biosynthetic processes, while Keto treatment upregulated genes relevant to blood vessel formation and cell migration in male placentae. Brain transcriptomes were minimally affected. X-linked genes and chromatin modifiers were identified as differentially expressed, alluding to a sex-specific regulatory mechanism. Transient preimplantation ketone exposure therefore perturbs sex-specific fetal liver and placental gene expression demonstrating a developmental programming effect that warrants future investigation of male and female offspring postnatal metabolic health.
2023-09-15 | GSE217821 | GEO
Project description:Assisted Reproductive Technologies (ART) employ gamete/embryo handling and culture in vitro to produce offspring. ART pregnancies have increased risk of low birth weight, abnormal placentation, pregnancy complications, and imprinting disorders. We and others have previously shown that embryo culture induces low birth weight, abnormal placental morphology, and lower levels of DNA methylation in placentas in a mouse model of ART. We hypothesized that these adverse effects are linked to a subtle disruption of specific biological processes during preimplantation development. To test this hypothesis, we performed embryo culture for several discrete periods of preimplantation development and assessed fetal and placental outcomes at term. We observed a reduction in fetal:placental ratio in two distinct windows of preimplantation embryo development, while placental morphological abnormalities and reduced imprinting control region methylation were associated with culture prior to the morula stage. We also provide evidence that extended culture to the blastocyst stage induces additional placental DNA methylation changes compared to embryos transferred at the morula stage, and that female concepti exhibited a higher loss of DNA methylation than males. Altogether, this study identifies specific developmental windows of susceptibility and potential targets for embryo culture optimization.
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Project description:Targeting Ketone Body Metabolism in Mitigating Gemcitabine Resistance
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Project description:Preimplantation mouse embryo development on Affymetrix MOE430B. Zeng et al (2004) Dev Biol 272:483-496. Keywords: other
2004-09-10 | GSE1745 | GEO
Project description:Preimplantation mouse embryo development study on Affymetrix MOE430A. Zeng et al (2004) Dev Biol 272:483-496. Keywords: other
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Project description:Preimplantation mouse embryo development study on Affymetrix U74Av2. Zeng et al Dev Biol (2004) 272:483-496. Keywords: other
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Project description:Diets characterized by increased blood levels of ketone bodies can protect the brain against a variety of acute and chronic neurological diseases. Moreover, ketone bodies are neuroprotective in many in vitro models of neurological injury. The underlying mechanisms remain unknown however. Recently, we have shown that ketone bodies do not only decrease neuronal injury and death but also protect long-term potentiation in acute hippocampal slices exposed to oxidative stress in the form of exogenous hydrogen peroxide. Elucidating the mechanisms behind the effects of ketone bodies on neuronal survival and function will undoubtedly lead to the development of novel neuroprotective treatments. Our aim is to determine acute changes in gene expression of CA1 pyramidal neurons exposed to various duration of the ketone bodies acetoacetate and beta-hydroxybutyrate. CA1 hippocampal pyramidal neurons exposed to oxidative stress do not display any long-term potention following burst stimulation of Schaffer collaterals. Incubation with the ketone bodies acetoacetate and beta-hydroxybutyrate for at least 20 min prior to hydrogen peroxide application restores long-term potentiation to control levels. We hypothesize that the neuroprotective effects of ketone bodies are mediated by changes in gene expression. Acute hippocampal slices (400 microns in thickness) were obtained from 4 week-old rats and exposed to acetoacetate and beta-hydroxybutyrate (1 mM each) for 1 h and 6 h. A control group was incubated in artificial cerebrospinal fluid only. After treatment, the hippocampal slices were used immediately for RNA isolation. Isolated RNA was sent for analysis. Each sample sent for analysis included tissue from 7 separate animals. Hybridization to an Affymetrix array is being performed 3 times for each experimental condition.
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Project description:Preimplantation mouse embryo development study on Affymetrix MOE430A. Zeng et al (2004) Dev Biol 272:483-496.
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Project description:Purpose: The goals of this study are to define transcriptome (RNA-seq) of mouse preimplantation embryos at different stages of development under a range of different environmental conditions. Methods: Mouse preimplantation embro transcriptional profiles were generated using embryos at several different developmental stages using Smart-seq2. Results: RNA-seq analysis finds that there is a highly dynamic pattern of gene expression during the preimplantation period. The sensitiivty to nutrient conditions varies markedly at different stages of development, with 2C embryos more sensitive to pyruvate omission than later stage embryos. Conclusions: Our study represents a comprehensive analysis of the mouse preimplantation development transcriptome, and how pyruvate provision impacts different developmental stages.
2020-10-14 | GSE159484 | GEO
Project description:Developing embryos are susceptible to fluctuations in the nutrients and metabolites concentrations within the reproductive tract, which can lead to alterations in their developmental trajectory. Ketotic dairy cows have diminished fertility, and elevated levels of the ketone body beta-hydroxybutyrate (BHB) have been associated with poor embryonic development. We used an in vitro model based on either in vitro fertilization (IVF) or parthenogenesis to investigate the effects of BHB on the preimplantation bovine embryo development, epigenome, and transcriptome. Embryo culture medium was supplemented with BHB at a similar concentration to that present in the blood of cows suffering with severe ketosis, followed by analysis of blastocysts formation rate, diameter, total number of cells, levels of H3K9 beta-hydroxybutyrylation (H3K9bhb), apoptosis, and transcriptional alterations. As a result, we observed that BHB reduced the blastocysts rates, the diameter and the total number of cells in both parthenotes and IVF embryos. Exposure to BHB for either 3 or 7 days greatly increased the H3K9bhb levels in parthenotes at the 8-cells and blastocyst stages, and affected the expression ofHDAC1,TET1,DNMT1,KDM6B,NANOGandMTHFD2genes. Additionally, culture of IVF embryos with BHB for 7 days dramatically increased H3K9bhb and reduced NANOG in blastocysts. RNA-seq analysis of IVF blastocysts revealed that BHB modulated the expression of 118 genes, which were involved with biological processes such as embryonic development, implantation, reproduction, proliferation, and metabolism. These findings provided valuable insights into the mechanisms through which BHB disrupts preimplantation embryonic development and affects the fertility in dairy cows.
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