Rats were exposed to sub-chronic low doses of the the germ cell toxicant 1,2-dibromo-3-chloropropane (DBCP) or corn oil (control for DBCP), for 3 months. Some rats in each group underwent 3 months of post-exposure recovery.
No associated publication
Specimen part, Treatment
View SamplesCurrent human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat.
Sperm mRNA transcripts are indicators of sub-chronic low dose testicular injury in the Fischer 344 rat.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm.
No sample metadata fields
View SamplesDietary restriction (DR) is one of the most studied interventions known to extend life span. The robustness of its effect across species suggests the existence of conserved mechanisms to reduce mortality rates and increase longevity. However, because DR elicits a large number of physiological changes, many of which are unrelated to the longevity response, it has been difficult to identify these specific mechanisms. Whole-genome gene expression studies have typically reported several hundreds to thousands of differentially expressed genes in response to DR. The fruit fly Drosophila melanogaster shows a remarkable response to a change in diet: after a switch to DR, food mortality rates drop within 2-4 days to the same level as cohorts continuously on DR. Based on this observation, we utilized a novel experimental design to enrich for genes directly associated with the longevity response. By profiling gene expression in a cohort of fruit flies that were switched from normal food to DR we were able to partition genes in several classes with distinct patterns of expression.
No associated publication
Sex, Age, Specimen part
View SamplesMYC is a pleiotropic transcription factor that regulates numerous pathways and whose deregulation promotes cancer. Myc+/- mice have extended lifespan relative to their wild type littermates. To better understand the effects of the Myc+/- genotype on cellular processes, microarrays were performed on young (5 month) and old (24 month) Myc+/- and WT males in liver, skeletal muscle, and adipose tissues.
Reduced expression of MYC increases longevity and enhances healthspan.
Sex, Age, Specimen part
View SamplesAkt1 plays a protective role in the postnatal C57BL6 mouse testis following lactational exposure to the neonatal goitrogen, propylthiouracil (PTU). To elucidate the transcriptional profile mediating this phenotypic effect, we monitored changes in testicular gene expression at postnatal days (PNDs) 15 and 25 in Akt1+/+, Akt1+/-, and Akt1-/- testes following exposure to 0.01% PTU allowing us to determine changes in gene expression due to 1.) genotype effects; 2.) exposure effects; and 3.) genotype-by-exposure interactions. Early PTU-dependent gene changes included genes involved in lipid metabolism, spermatid differentiation, meiosis and adhesion. Early Akt1-dependent effects were associated with germ cell development, spermatid development and differentiation, and sperm motility. By PND25, the Akt1 gene-environment interaction had pronounced effects on genes associated with Sertoli cell (SC) differentiation and claudin-associated junctional formation suggesting delayed formation of the blood-testis barrier (BTB). To confirm these observations, biotin tracer experiments demonstrated a permeable blood-testis barrier in PTU-exposed PKBalpha/Akt1-/- tubules as late as PND25 compared to PTU-exposed Akt1+/+ seminiferous tubules. Transmission electron microscopy demonstrated altered SC morphology, aberrant SC localization, and disorganized actin bundle formation. Taken together, loss of Akt1 coupled with postnatal exposure to the neonatal goitrogen, PTU, in the testis contributes to a transcriptional profile associated with impaired integrity of the blood-testis barrier. In summary, the Akt1-/- mouse represents a potentially important model to study BTB formation and reassembly in response to male reproductive toxicants and the various signaling networks which mediate these responses.
No associated publication
Sex, Treatment
View SamplesNovel approaches were used to generate the DNA sequence information for the rhesus GeneChip (2005). The purpose of this experiment was to test its reliability and validity of the rhesus macaque GeneChip across different tissues and centers.
Intercenter reliability and validity of the rhesus macaque GeneChip.
Specimen part, Cell line
View SamplesType 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4- dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 as compared to STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation.
Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function.
Age, Specimen part, Treatment
View SamplesExpression profiling of pulmonayr fibrosis prone and fibrosis resistant strains of mice with transgenic overexpression of TGF-beta1
Laminin α1 is a genetic modifier of TGF-β1-stimulated pulmonary fibrosis.
Treatment
View SamplesThe primary goal of this study was to compare the performances of Rhesus Macaque Genome Array and Human Genome U133 Plus 2.0 Array with respect to the detection of differential expressions when rhesus macaque RNA extracts were labeled and hybridized.
Large scale analysis of positional effects of single-base mismatches on microarray gene expression data.
Specimen part, Cell line
View Samples