No description.
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View SamplesMammalian females are born with a finite number of non-renewing primordial follicles, the majority of which remain in a quiescent state for many years. Due to their non-renewing nature, these resting oocytes are particularly vulnerable to xenobiotic insult, resulting in premature ovarian senescence and the formation of dysfunctional oocytes. In this study we characterised the mechanisms of ovotoxicity for three ovotoxic agents, 4-Vinylcyclohexene Diepoxide (VCD), Methoxychlor (MXC), and Menadione (MEN), all of which target immature follicles. Neonatal mouse ovaries (PND3-4) were cultured in the presence of 4-Vinylcyclohexene Diepoxide (50uM), Methoxychlor (50uM), and Menadione (5uM) for 96 hours to observe their effects on the ovarian transcriptome. This was done in the hopes of gaining a better understanding of the mechanisms underpinning xenobiotic induced pre-antral ovotoxicity.
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Specimen part
View SamplesIn this study the generic impact of protein aggregation (aggregation of proteins not associated with neurodegenerative disease) on gene expression in cultured cells was investigated by DNA microarray technology. The survey of gene expression showed that the Hsp40, Hsp70 and Hsp105 genes, all of which have documented aggregation suppression activity, were up-regulated. Unexpectedly, the survey also showed increased expression of the MEK5 gene with concomitant silencing of the MEK3 gene. The expression pattern of MEK5 at the mRNA and protein levels aligns with the kinetics of aggregate formation and dissolution. Cell viability was unaffected by protein aggregates. These findings are of particular importance for chronic neurodegenerative diseases where the intraneuronal accumulation of aggregate-prone proteins are a major characteristic of the diseases. The identification of changes in MEK5 gene expression have been observed in Alzheimer-related diseases which provides new diagnostic and therapeutic avenues in these diseases. The molecular neuropathological findings would not have occurred without the generic microarray analyses.
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Specimen part, Cell line, Time
View Samplesthe first study to comprehensively explore the effects of EriB in zebrafish model using a transcriptome analysis approach.
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View SamplesDespite the documented benefits of breastfeeding and major governmental advocacy efforts, a paucity of data exists regarding the transfer of most drugs into breast milk. Passive diffusion governs the extent of accumulation for most drugs and the exposure risk can therefore be predicted using mathematical models. However, examples of xenobiotic accumulation into breast milk well above that predicted by passive diffusion have been documented and attributed to drug transport. A thorough evaluation of the expression of xenobiotic transporters in mammary epithelial cells (MECs), the cells that form the anatomical barrier between maternal serum and breastmilk, during lactation is necessary to determine the drugs for which an active transport mechanism governs transfer into breast milk and to improve predictive models.
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Age, Specimen part, Disease
View SamplesA long form (tRNase ZL) of tRNA 3' processing endoribonuclease (tRNase Z, or 3' tRNase) can cleave any target RNA at any desired site under the direction of artificial small guide RNA (sgRNA). We discovered in human kidney 293 cell extracts various new small noncoding RNAs (ncRNAs) including 5'-half-tRNAs and 28S rRNA fragments, co-immunoprecipitated with tRNase ZL, and demonstrated that two of these ncRNAs work as sgRNAs for tRNase ZL in vivo as well as in vitro. In order to find genuine mRNA targets of tRNase ZL guided by ncRNAs, we performed DNA microarray analysis for mRNAs from the 293 cells transfected with the tRNase ZL expression plasmid, and found that PPM1F and DYNC1H1 mRNAs are its genuine targets.
Modulation of gene expression by human cytosolic tRNase Z(L) through 5'-half-tRNA.
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View SamplesGenome-wide analysis of decidual transcriptome in pre-eclampsia compared with normotensive controls to find differentially expressed genes/pathways.
Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes.
Specimen part, Disease stage
View SamplesAnalysis of mouse placenta retrieved at day 18.5pc from vitamin D (1,25-dihydroxyvitamin D3) receptor (Vdr) knockout, heterozygous and wild-type mice. Results provide insight into the molecular mechanisms underlying the effect of vitamin D on placental function.
Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome.
Specimen part
View SamplesReduced or absent cytotrophoblast invasion of the maternal uterine spiral arteries is a common clinical finding in studies of pregnancies complicated by preeclampsia, suggesting that the mechanisms behind invasion of these cells is perturbed. The placenta initially develops in a low oxygen environment of 1-2% oxygen until after the 10th week of pregnancy. During this time oxygen concentration exerts a major influence over trophoblast activity and, in vitro, hypoxia inducible factors are proposed to be one of many key regulators of first trimester trophoblast behaviour. We used a global gene expression microarray approach to identify signalling pathways involved in invasion of the first trimester trophoblast cell line HTR8/SVneo under hypoxic conditions where HIF-1 was active. Additionally, first trimester placental samples from different gestational age groups were labelled with anti HIF-1 and HIF-2 to evaluate whether HIFs are differentially expressed and localised across the period of development characterised by hypoxia (6-8 weeks) and maternal blood perfusion (10-12 weeks). Eighty-eight genes were differentially expressed between cells cultured in 1% oxygen (where HIF-1 was localised to the nucleus) and 5% oxygen (where HIF-1 was cytoplasmic). 65% of the genes were predicted to contain HIF-1:ARNT transcription factor binding sites. Increased nuclear localisation of HIF-1 was seen in extravillous cytotrophoblasts in early first trimester compared with late, while cellular expression of HIF-2 in the villous stroma was higher in late first trimester. While HIFs and their downstream targets are clearly induced in trophoblasts during early placental development, and in vitro hypoxic conditions, the mechanism and pathways by which invasion is increased under hypoxic conditions is not clear from the gene expression profile. Further insight beyond the transcription level is required to fully understand this complex phenomenon.
Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion.
Cell line, Treatment
View SamplesPrenatal exposure to valproic acid, an established anti-epileptic drug, has been reported to impair postnatal cognitive function of children from epileptic mothers. Nevertheless, its pathology and proper treatment to minimize the effects remain unknown. In mice, we found that the postnatal cognitive function impairment was mainly caused by a reduction of adult neurogenesis and abnormal neuronal features in the hippocampus, which could be ameliorated by voluntary running.
Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid.
Sex, Specimen part, Treatment
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