Hdac inhibition and axial malformations
Di Renzo, F; Luisa Broccia, ML; Menegola, E; Giavini, E
HERO ID
1455505
Reference Type
Journal Article
Subtype
Abstract
Year
2006
Language
English
| HERO ID | 1455505 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 2006 |
| Title | Hdac inhibition and axial malformations |
| Authors | Di Renzo, F; Luisa Broccia, ML; Menegola, E; Giavini, E |
| Journal | Reproductive Toxicology |
| Volume | 22 |
| Issue | 2 |
| Page Numbers | 269-270 |
| Abstract | The inhibition of histone deacetylases (HDAC) has been recently suggested as a new mechanism of teratogenesis. Embryonic HDAC inhibition has been demonstrated after dosage of pregnant mice with valproic acid and trichostatin A, and has been correlated, at term of gestation, to typical foetal skeletal abnormalities (axial duplications and respecifications). To better define the relationship between HDAC inhibition and axial abnormalities, in the present work we intraperitoneally treated pregnant mice on day 8 post-coitum with molecules known as HDAC inhibitors in adult cells (butyric acid, apicidin, MS275) but unknown for their teratological profile, or with boric acid (a teratogenic agent able to induce axial malformations but with an unknown mechanism of action). Some females were killed a few hours after the treatment; embryos were processed for immunoblotting or immunohistochemistry by using an antibody anti-hyperacetylated histone H4. The remaining females were sacrificed at term of gestation; foetuses were processed for the skeletal double staining for bone and cartilage. All the tested molecules induced embryonic H4 hyperacetylation, as shown by immunoblot. Interestingly, the immunohistochemistry revealed somites as target organs (according to the results obtained after valproic acid and trichostatin A treatment). Axial malformations were observed in foetuses treated with all the tested substances. The data obtained: (1) confirm the relationship between HDAC inhibition and axial abnormalities; (2) confirm that the somites are the main target organs for this class of molecules; (3) suggest that the HDAC inhibition could be the mechanism on the basis of the boric acid-related axial abnormalities. |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |