Fescue toxicosis affects wild and domestic animals consuming ergot alkaloids contained in tall fescue forage infected with the endophytic fungus, Neotyphodium coenophialum. When animals are consuming infected fescue (E+) forage during periods of elevated ambient temperatures (summer), a range of phenotypic disorders collectively called summer slump is observed. It is characterized by hyperthermia, with an accompanying decrease in feed intake, growth, milk yield, and reproductive fitness. Laboratory mice also exhibit symptoms of fescue toxicosis at thermo-neutral (TN) temperature, as indicated by reduced growth rate and reproductive fitness. Our goal was to characterize the differences in gene expression in liver of mice exposed to summer-type heat stress (HS) and E+ when compared to mice fed E+ at TN temperature. Mice were fed E+ diet under HS (34 +/- 1 degrees C; n = 13; E+HS) or TN conditions (24 +/- 1 degrees C; n = 14; E+TN) for a period of 2 weeks between 47 and 60 days of age. Genes differentially expressed between E+HS versus E+TN were identified using DNA microarrays. Forty-one genes were differentially expressed between treatment groups. Expressions of eight genes were measured using quantitative real-time PCR. Genes coding for phase I detoxification enzymes were upregulated in E+HS mouse liver. This detoxification pathway is known to produce reactive oxidative species. We observed an upregulation of genes involved in the protection against reactive oxidative species. Key genes involved in de novo lipogenesis and lipid transport were also upregulated. Finally, genes involved in DNA damage control and unfolded protein responses were downregulated.
Interferon-tau (IFNT) is released by preimplantation conceptuses of ruminant species and prepares the mother for pregnancy. Although one important function is to protect the corpus luteum from the luteolytic activity of prostaglandin-F 2alpha, IFNT most likely regulates a range of other physiological processes in endometrium. Here, an immortalized cell line from ovine uterine luminal epithelial cells was treated with IFNT for either 8 or 24 h. RNA was subjected to cDNA microarray analysis, with RNA from untreated cells as the reference standard. Of 15 634 genes, 1274 (8%) were IFNT responsive at P<0.01 and 585 at P<0.001 to at least one treatment. Of the latter, 356 were up-regulated and 229 down-regulated. Increasing IFNT concentrations from 10 ng/ml to 10 microg/ml had minor effects, and most genes up- or down-regulated at 8 h were regulated similarly at 24 h. Although IFNT influences many genes implicated in antiviral activity and apoptosis, its action also likely regulates prostaglandin metabolism, growth factors and their receptors, apoptosis and the nuclear factor (NF)-kappaB cascade, extracellular matrix accretion, angiogenesis, blood coagulation, and inflammation. In particular, it increased mRNA concentrations of genes related to the vascular endothelial growth factor R2 pathway of angiogenesis and down-regulated ones associated with hypoxia. Two genes implicated in the antiluteolytic actions of IFNT (encoding cyclooxygenase-2 and the oxytocin receptor respectively) were down-regulated in response to all treatments. IFNT targets a complex range of physiological processes during the establishment of pregnancy.
In mono-ovulatory species, one follicle is selected from a cohort of antral follicles to continue its growth and development. The other follicles from the cohort will ultimately undergo atresia. Understanding the mechanisms by which a single follicle is selected for further development and dominance in a hormonal milieu suppressive to the development of other large follicles is key to understanding preovulatory follicular development. Microarrays (17,692 cDNA probes) were used to identify genes differentially expressed among fourteen bovine follicles (8 to 11.5mm in diameter). First, follicles were organized in three groups according to the time from initiation of the wave (24H, 36H, 48–60H). Fifty nine genes (59) were identified as differentially expressed with a cut off false discovery rate (FDR) of 0.05 (adjusted for multiple testing) and a minimum of 40% up or down-regulation. Genes involved in immune related functions are up regulated in the 36 hour group. Genes regulating cell division/cell cycle and cell/extracellular matrix attachment were up or down regulated in the 36 and 48/60 hour groups. Follicles were also grouped according to the estimated time of deviation; early deviation (8 mm), middle deviation (8.5mm), late deviation (9mm) and dominant follicles (>9mm). One hundred and seventy six (176) differentially expressed genes were identified. Genes involved in immune-related functions and the mitotic cell cycle were up-regulated in the middle and late deviation groups. Annotation of the cellular location of the products identified non-membrane-bound organelle and the extracellular matrix as over-represented. Finally, fifty five genes have an expression pattern highly positively correlated with the expression of the LH receptor and ninety eight genes are negatively correlated. Expression profiles of seventeen genes were confirmed using quantitative RT-PCR. (poster)