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GSE33830
Rattus norvegicus
132 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Sexual selection involves mate preference behavior and is a critical determinant for natural selection and evolutionary biology. Previously an environmental compound (fungicide vinclozolin) was found to promote epigenetic transgenerational inheritance of modified mate selection characteristics in all progeny for three generations after exposure of a gestating female. The current study investigated gene networks involved in various regions of the brain that correlated with the mate preference behavior altered in F3-Vinclozolin lineage animals. Statistically significant correlations of differentially expressed gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified critical gene networks involved in mate preference behavior and demonstrated the ability of environmental factors to promote epigenetic transgenerational inheritance of this altered evolutionary biology determinant. Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology.
Publication Title
Gene bionetworks involved in the epigenetic transgenerational inheritance of altered mate preference: environmental epigenetics and evolutionary biology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 66 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Environmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes suggesting a general alteration in genome activity. Investigation of eleven different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had unique transgenerational transcriptomes. Common cellular pathways and processes were identified among the tissues. A bionetwork analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue specific gene expression and function. A large number of statistically significant over-represented clusters of differentially expressed genes were identified and termed Epigenetic Control Regions. Combined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome appear to in part coordinately regulate these tissue specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes.
Publication Title
Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 48 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Ancestral environmental exposures that promote epigenetic transgenerational inheritance influence all aspects of an individuals life history. Stress experienced during adolescence can affect adult physiological and behavioural phenotypes. The current study utilized a systems biology approach to investigate the interactions of these two forms of epigenetic modification, one carried in the germline transgenerationally and the other contained in the context of life history. A transgenerational epigenetic imprint left by the fungicide vinclozolin promoted regional specific brain gene networks that influenced chronic restraint stress responses to alter adult physiological, brain and behavioural phenotypes. The environmentally-induced epigenetic transgenerational inheritance was found to interact with early life stress response to impact the adult brain genome activity to bring the phenotype into being.
Publication Title
Epigenetic transgenerational inheritance of altered stress responses.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 44 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Ovarian primordial follicles are critical for female reproduction and comprise a finite pool of gametes arrested in development. A systems biology approach was used to identify regulatory gene networks essential for primordial follicle development. Transcriptional responses to eight different growth factors known to influence primordial follicles were used to construct a bionetwork of regulatory genes involved in primordial follicle development. Over 1500 genes were found to be regulated by the various growth factors and a network analysis identified critical gene modules involved in a number of signaling pathways and cellular processes. A set of 55 genes was identified as potential critical regulators of these gene modules, and a subnetwork associated with development was determined. Within the network two previously identified regulatory genes were confirmed (i.e. Pdgfa and Fgfr2) and a new factor was identified, connective tissue growth factor (CTGF). CTGF was tested in ovarian organ cultures and found to stimulate primordial follicle development. Therefore, the relevant gene network associated with primordial follicle development was validated and the critical genes and pathways involved in this process were identified. This is one of the first applications of network analysis to a normal developmental process. These observations provide insights into potential therapeutic targets for preventing ovarian disease and promoting female reproduction.
Publication Title
Gene bionetwork analysis of ovarian primordial follicle development.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Primordial follicle assembly is the process by which ovarian primordial follicles are formed. During follicle assembly oocyte nests break down and a layer of pre-granulosa cells surrounds individual oocytes to form primordial follicles. The pool of primordial follicles formed is the source of oocytes for ovulation during a females reproductive life. Complex networks of cellular signaling and gene expression are essential for any biological process. A systems biology experimental approach provides a global view of these gene relationships in a particular developmental process. The current study utilized a systems approach to detect all genes that are differentially expressed in response to seven different growth factor and hormone treatments known to influence primordial follicle assembly in a neonatal rat ovary culture system. One novel growth factor, basic fibroblast growth factor (FGF2), was experimentally determined to inhibit follicle assembly. The different growth factor and hormone treatments were all found to affect the same physiological pathways, but each treatment affected a unique set of differentially expressed genes (signature gene set). A gene bionetwork analysis identified gene modules of coordinately expressed interconnected genes and it was found that different gene modules appear to accomplish distinct tasks during primordial follicle assembly. Unique gene networks were identified for a number of the modules and signature gene sets. Predictions of physiological pathways important to follicle assembly were validated using ovary culture experiments in which ERK1/2 (MAPK1) activity was increased. A number of the highly interconnected genes in these gene networks have previously been linked to primary ovarian insufficiency (POI) and polycystic ovarian disease syndrome (PCOS). Observations have identified novel factors and gene networks that regulate primordial follicle assembly. This systems approach has helped elucidate the molecular control of primordial follicle assembly and provided potential therapeutic targets for the treatment of ovarian disease.
Publication Title
Gene bionetworks that regulate ovarian primordial follicle assembly.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.
Publication Title
Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The current study investigates the direct effects of in utero vinclozolin exposure on the developing rat testis transcriptome. Vinclozolin is a commonly used fungicide in agriculture and is an endocrine disruptor with anti-androgenic activity. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states that include spermatogenic cell defects, prostate disease, kidney disease, and tumor development. An investigation of the molecular actions of vinclozolin was initiated through an analysis of direct actions on the F1 generation embryonic testis development. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Interestingly, genes previously shown to be regulated during normal male sex determination were not altered by vinclozolin treatment. Categorization by major known functions of all 576 genes altered by in utero vinclozolin exposure demonstrates transcription, signaling, cytoskeletal and extra cellular matrix associated transcripts are highly represented. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin.
Publication Title
Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex-determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response element both in vitro and in vivo during male sex determination. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to promote precursor Sertoli cell differentiation. Therefore, SRY acts directly on the Tcf21 promoter to, in part, initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development.
Publication Title
Basic helix-loop-helix transcription factor TCF21 is a downstream target of the male sex determining gene SRY.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 14 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Embryonic day 13 (E13), E14, and E16 rat testes and ovaries were used for microarray analysis, as well as E13 testis organ cultures that undergo testis morphogenesis and develop seminiferous cords in vitro. A list of 109 genes resulted from a selective analysis for genes present in male gonadal development and with a 1.5-fold change in expression between E13 and E16. Characterization of these 109 genes potentially important for testis development revealed that cytoskeletal-associated proteins, extracellular matrix factors, and signaling factors were highly represented. Throughout the developmental period (E13-E16), sex-enriched transcripts were more prevalent in the male with 34 of the 109 genes having testis-enriched expression during sex determination. In ovaries, the total number of transcripts with a 1.5-fold change in expression between E13 and E16 was similar to the testis, but none of those genes were both ovary enriched and regulated during the developmental period. Genes conserved in sex determination were identified by comparing changing transcripts in the rat analysis herein, to transcripts altered in previously published mouse studies of gonadal sex determination. A comparison of changing mouse and rat transcripts identified 43 genes with species conservation in sex determination and testis development. Profiles of gene expression during E13-E16 rat testis and ovary development are presented and candidate genes for involvement in sex determination and testis differentiation are identified. Analysis of cellular pathways did not reveal any specific pathways involving multiple candidate genes. However, the genes and gene network identified influence numerous cellular processes with cellular differentiation, proliferation, focal contact, RNA localization, and development being predominant.
Publication Title
Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples