719 ESTROGEN EXPOSURE EPIGENETICALLY DOWN REGULATES EXPRESSION OF GENES CRITICAL FOR GENITAL TUBERCLE (GT) FORMATION IN HUMAN FORESKIN FIBROBLASTS
Bibliographic record
Abstract
You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2012719 ESTROGEN EXPOSURE EPIGENETICALLY DOWN REGULATES EXPRESSION OF GENES CRITICAL FOR GENITAL TUBERCLE (GT) FORMATION IN HUMAN FORESKIN FIBROBLASTS Karen Aitken, Jiaxin Jiang, Nicole Zhang, Tyler Kirwan, Cornelia Tolg, and Darius Bagli Karen AitkenKaren Aitken Toronto, Canada More articles by this author , Jiaxin JiangJiaxin Jiang Toronto, Canada More articles by this author , Nicole ZhangNicole Zhang Toronto, Canada More articles by this author , Tyler KirwanTyler Kirwan Toronto, Canada More articles by this author , Cornelia TolgCornelia Tolg Toronto, Canada More articles by this author , and Darius BagliDarius Bagli Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.804AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Xenoestrogen (XE) exposure increases the rate of hypospadias in both animal models and in humans. The molecular basis of XE effects on genital tubercle (GT) development is not clear. This study examines the epigenetic effects of XE on GT developmental genes, as well as on DNA methylation enzymes (DNMTs) involved in epigenetic downregulation. METHODS The BJ normal human foreskin fibroblast (HuFF) cell line was used to model GT mesenchyme. HuFF were stimulated every 24 hours with 100 nM of diethylstibestrol (DES) for 6, 24, 48 and 120 hours +/- 5-aza-2′deoxycytidine (aza), a DNMT inhibitor. Real-time PCR was performed to examine expression of candidate genes (WNT5A, HoxA13, HoxA10, DNMT-1,-3A and -3B, and others), normalized to rpl19 or gapdh. RESULTS DNMTs were all temporally upregulated significantly by DES treatment: 75% at 6 hours for DNMT3A (p<0.05), >2 fold at 120 hours for DNMT1 (p<0.005), and >5 fold at 6, 24 and 120 hours for DNMT3B. Hox and WNT5A gene expression was conversely downregulated by DES and partially restored by aza. HoxA13 was downregulated between 70-92% at 24, 48 and 120 hours of DES treatment (p<0.05). Aza recovered expression of HoxA13 by 3-fold (p<0.04) by day 5. At 48 hours, Wnt5A also showed downregulated expression, which was increased 5.6-fold by aza (p<0.02), though at other time points was not similarly affected by DES. CONCLUSIONS DES treatment activates the epigenetic machinery, via increased DNMT expression. This epigenetic response is accompanied by a down regulation of WNT5A and HoxA13, genes critical for GT formation. This downregulation is dependent on DNA methylation as DNMT inhibition with aza partially restores HoxA13 and WNT5A expression. These results suggest that environmental XE may act epigenetically to induce long-term alterations in genes crucial for genital development. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e295 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karen Aitken Toronto, Canada More articles by this author Jiaxin Jiang Toronto, Canada More articles by this author Nicole Zhang Toronto, Canada More articles by this author Tyler Kirwan Toronto, Canada More articles by this author Cornelia Tolg Toronto, Canada More articles by this author Darius Bagli Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".