Genetic differences in estrous cycle effects on the rat brain transcriptome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA667342 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12772600_1.fastq.gz | Fastqsanger.gz | |||
| SRR12772600_2.fastq.gz | Fastqsanger.gz | |||
| SRR12772601_1.fastq.gz | Fastqsanger.gz | |||
| SRR12772601_2.fastq.gz | Fastqsanger.gz | |||
| SRR12772602_1.fastq.gz | Fastqsanger.gz |
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Project description:Males and females often differ on propensity for a substance use disorder (SUD), etiology and clinical manifestation of SUD, and response to SUD treatment strategies (Riley et al 2018). The fluctuation of sex-related hormones in the brain and/or circulation may contribute to some of these differences. For example, estradiol activity has been associated with sensitivity to drugs of abuse (Tonn Eisinger et al 2018) and vulnerability to SUD (Anker and Carroll 2011). In particular, estrogen can affect the dopamine system in brain and this may contribute to differences in the etiology and the clinical manifestation of SUD (Bobzean et al 2014). Without direct association with SUD, others have shown that stage of the estrous cycle influences RNA transcription levels and splicing in particular brain regions (Duclot and Kabbaj 2015; DiCarlo et al 2017). What has not been thoroughly explored is whether genetic factors can modify the effect of estrous cycle on RNA transcript and ultimately, whether the interaction of these two factors can influence the sex-related differences in SUD vulnerability.
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Project description:Hormonal fluctuations throughout the ovarian cycle contribute to females’ higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC.
2015-10-23 | GSE69765 | GEO
Project description:Hormonal fluctuations throughout the ovarian cycle contribute to females’ higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC.
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Project description:Hormonal fluctuations throughout the ovarian cycle contribute to femalesâ?? higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC. Early growth response 1 (Egr1) binding profiling in the adult rat medial prefrontal cortex of males, proestrus females, and diestrus females. A total of 9 animals were used, corresponding to 3 Males, 2 proestrus females, and 4 diestrus females.
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Project description:Hormonal fluctuations throughout the ovarian cycle contribute to femalesâ higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC. mRNA profiling of 2-3 month-old males and females Sprague-Dawley rats in either Proestrus or Diestrus. A total of 11 samples were analyzed, corresponding to 4 males, 3 proestrus females, and 4 diestrus females.
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Project description:The influence of the estrous cycle on sex differences in the rat adult medial prefrontal cortex transcriptome
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Project description:We analyzed the transcriptome of the C57BL/6J mouse hypothalamus, hippocampus, neocortex, and cerebellum to determine estrous cycle-specific changes in these four brain regions. We found almost 16,000 genes are present in one or more of the brain areas but only 210 genes, ~1.3%, are significantly changed as a result of the estrous cycle. The hippocampus has the largest number of differentially expressed genes (DEGs) (82), followed by the neocortex (76), hypothalamus (63), and cerebellum (26). Most of these DEGs (186/210) are differentially expressed in only one of the four brain regions. A key finding is the unique expression pattern of growth hormone (Gh) and prolactin (Prl). Gh and Prl are the only DEGs to be expressed during only one stage of the estrous cycle (metestrus). To gain insight into the function of the DEGs, we examined gene ontology and phenotype enrichment and found significant enrichment for genes associated with myelination, hormone stimulus, and abnormal hormone levels. Additionally, 61 of the 210 DEGs are known to change in response to estrogen in the brain. 50 genes differentially expressed as a result of the estrous cycle are related to myelin and oligodendrocytes and 12 of the 63 DEGs in the hypothalamus are oligodendrocyte- and myelin-specific genes. This transcriptomic analysis reveals that gene expression in the female mouse brain is remarkably stable during the estrous cycle and demonstrates that the genes that do fluctuate are functionally related.
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