Gametes rely heavily on post-transcriptional control mechanisms to regulate their differentiation. In eggs, the storage and selective temporal activation of maternal mRNAs is essential for normal development. In the male, transcription ceases during spermiogenesis necessitating the post-transcriptional regulation of many paternal mRNAs required for spermatid differentiation and spermatozoan function. Messenger RNAs that are being actively translated form polysomes. whereas translationally inactive mRNAs are often sequestered in ribonucleoproteins (RNPs). Here we combine polysome display and microarray analyses of RNP and polysome fractions of testes from prepuberal and adult mice to characterize the translation state of individual mRNAs as spermatogenesis proceeds.. Consistent with published reports, many post-meiotic mRNAs known to be translationally delayed shift from the RNPs into the polysomes, confirming the validity of this approach. In addition, based upon the criterion of movement from RNPs to polysomes, we detect another 742 mouse testicular genes showing dramatic shifts between RNPs and polysomes. One sub-group of 35 genes including the known translationally delayed Pgk2, are initially transcribed and translationally repressed in meiotic spermatocytes, and translated post-meiotically. This high-through-put approach defines the changing translation patterns of a large number of genes as male germ cells differentiate and identifies a new group of post-transcriptionally regulated meiotic transcripts for future study.
Expression profiling reveals meiotic male germ cell mRNAs that are translationally up- and down-regulated.
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View SamplesDeprivation of peripheral nerve input by cochlear removal in young mice results in dramatic neuron death in the cochlear nucleus (CN). The same manipulation in older mice does not result in significant loss. The molecular basis of this critical period of vulnerability remains largely unknown. Here we identified genes regulated at early time points after cochlear removal at ages when neurons are vulnerable (postnatal day (P)7) or invulnerable (P21) to this challenge. Afferent deprivation regulated very different sets of genes at P7 and P21. These genes showed a variety of functions at both ages, but surprisingly there was no net increase in pro-apoptotic genes at P7. A large set of upregulated immune-related genes was identified at P21.
Afferent deprivation elicits a transcriptional response associated with neuronal survival after a critical period in the mouse cochlear nucleus.
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View SamplesWe analyzed whether cochlear removal-induced transcriptional changes in the cochlear nucleus (CN) were due to loss of electrical activity in the 8th nerve. Pharmacological activity blockade of the auditory nerve for 24 h resulted in similar expression changes for only a subset of genes. Thus, an additional factor not dependent on action potential-mediated signaling must also regulate transcriptional responses to deafferentation in the CN.
Afferent deprivation elicits a transcriptional response associated with neuronal survival after a critical period in the mouse cochlear nucleus.
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View SamplesDiethylstilbestrol (DES) inhibits the differentiation of female reproductive tracts during fetal and neonatal days . We examined global gene expressions in the oviduct, uterus and vagina in newborn mice with or without DES. These results suggest understanding the mechanism of the differentiation of female reproductive tracts.
Gene expression change in the Müllerian duct of the mouse fetus exposed to diethylstilbestrol in utero.
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View SamplesEstrogen induce organ-specific cell proliferation and development in female reproductive organs, though the reproductive differentiation, sex maturation, implantation and lactation. However, the mechanism of organ-specific estrogen responsive genes is unknown. Thus, we examined early estrogen responsive genes in mouse uterus, vagina and mammary gland.
Comparison of estrogen responsive genes in the mouse uterus, vagina and mammary gland.
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View SamplesDevelopmental exposure of mouse fetuses to estrogens results in dose-dependent permanent effects on prostate morphology and function. Fetal prostatic mesenchyme cells express estrogen receptor alpha (ER) and androgen receptors and convert stimuli from estrogens and androgens into signaling to regulate epithelial cell proliferation and differentiation. To obtain mechanistic insight into the role of different doses of estradiol (E2) in regulating mesenchymal cells, we examined E2-induced transcriptomal changes in primary cultures of fetal mouse prostate mesenchymal cells. Urogenital sinus mesenchyme cells were obtained from male mouse fetuses at gestation day 17 and exposed to 10 pM, 100 pM or 100 nM E2 in the presence of a physiological concentration of dihydrotestosterone (0.69 nM) for four days. Gene ontology studies suggested that low doses of E2 (10 pM and 100 pM) induce genes involved in cell adhesion, morphological tissue development, and sterol biosynthesis but suppress genes involved in growth factor signaling and cell adhesion. Genes showing inverted-U-shape dose responses (enhanced by E2 at 10 pM E2 but suppressed at 100 pM) were identified, and their enrichment in the glycolytic pathway was demonstrated. At the highest dose (100 nM), E2 induced genes enriched not only for cell adhesion but also steroid hormone signaling and metabolism, cytokines and their receptors, cell-to-cell communication, Wnt signaling, and TGF- signaling. These results suggest that prostate mesenchymal cells may regulate epithelial cells through direct cell contacts when estrogen level is low whereas soluble growth factors might play significant roles when estrogen level is high.
Dose-related estrogen effects on gene expression in fetal mouse prostate mesenchymal cells.
Sex, Specimen part
View SamplesDevelopmental estrogen exposure causes permanent alterations to mouse prostate development. Fetal prostatic mesenchyme cells regulate epithelial cell proliferation and differentiation, and alterations to mesenchymal regulation of prostate epithelial cell proliferation and differentiation may lead to permanent changes in gland structure and function. Our goal was to understand how mesenchymal cells convert estrogen signaling to stimuli that affect epithelial cells. We used microarrays to identify estrogen-induced transcriptomal changes in primary cultures of fetal mouse prostate mesenchymal cells.
Dose-related estrogen effects on gene expression in fetal mouse prostate mesenchymal cells.
Sex, Specimen part, Treatment
View SamplesWe investigated the molecular mechanisms for osteolytic bone metastasis by selecting human lung cancer cell line subpopulations with elevated metastatic activity and validating genes that are overexpressed in these cells. A bone-seeking squamous lung cancer cell line (HARA-B4) was established by sequentially injecting parental HARA cells into the left ventricle of male 5-week-old nude mice 4 times.
Involvement of CXCL14 in osteolytic bone metastasis from lung cancer.
Specimen part, Cell line
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