Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action.

Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Research Abstract Details 

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Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Abstract Text:

Christopher J Stodgell,Jennifer L Ingram,Melanie O'Bara,Barbara K Tisdale,Heinz Nau,Patricia M Rodier,

BACKGROUND: Valproic acid (VPA) exposure in utero has been associated with an increased risk of both neural tube defects and autism spectrum disorders (ASDs). The terata induced by VPA suggest interference with pattern formation. Retinoic acid produces similar terata and is known to act in part by increasing the expression of Hoxa1. We tested the hypotheses that exposure to VPA would alter the expression of Hoxa1 in rat embryos during times of normal Hoxa1 expression (d10.5-13.5) and that exposure at earlier and later stages would induce inappropriate expression. METHOD: Hoxa1 expression levels were determined by real-time PCR in individual embryos 1 h after exposure on gestational d10, 12, 13, 14, or 15. Additionally, teratogenic (4-yn-VPA) and nonteratogenic analogs of VPA (IE-VPA), retinoic acid (RA), and saline were compared for effects on Hoxa1 expression on d12. Embryos were allowed to develop for 1, 2, 4, 6, or 24 h, to follow the time course of effects. RESULTS: In utero exposure to VPA on gestational d10 and on d12-14 significantly increased the level of Hoxa1 expression compared to saline-exposed embryos at developmental ages prior to, during and after the normal expression period for this gene. On gestational d12, exposures to VPA and 4-yn-VPA significantly increased Hoxa1 expression at all sacrifice times, compared to saline-exposed embryos. RA significantly elevated Hoxa1 expression at all time points except 24-h post-treatment. The nonteratogenic VPA analog, IE-VPA, did not affect Hoxa1 expression. CONCLUSIONS: VPA and 4-yn-VPA exposures elevated Hoxa1 mRNA during its normal expression period and induced expression outside of the normal period. This may explain, in part, how VPA disrupts development.

Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Publishing Authors By Initials

CJ Stodgell,JL Ingram,M O'Bara,BK Tisdale,H Nau,PM Rodier,

For similar organic chemicals: carboxylic acids: acids, acyclic: valerates: pentanoic acids: valproic acid research abstracts see: organic chemicals: carboxylic acids: acids, acyclic: valerates: pentanoic acids: valproic acid research

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Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Neurotoxicology and teratology

VOLUME: 28

Page Numbers: 617-24

Journal Abbreviation:

ISSN: 0892-0362

DAY: 16

MONTH: 08

YEAR: 2006

Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8709538

Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Keywords Mesh Terms:

KEYWORDS: Valproic Acid

MESH TERMS: toxicity

Chemical & Substance for Abstract: Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Information

Substance Name: Valproic Acid

Registry Number: 99-66-1

Grant and Affiliation Information for Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action.

AFFILIATION: Department of Obstetrics and Gynecology, University of Rochester, Rochester, NY, United States. Chris_Stodgell@urmc.rochester.edu <Chris_Stodgell@urmc.rochester.edu>

Country: United States

AGENCY: United States NICHD

GRANT: R01HD34969

ACRONYM: HD

MEDLINETA: Neurotoxicol Teratol

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