Document Detail


Embryonic exposure to propylthiouracil disrupts left-right patterning in Xenopus embryos.
MedLine Citation:
PMID:  23150524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Antithyroid medications are the preferred therapy for the treatment of Graves' disease during pregnancy. Propylthiouracil (PTU) is favored over methimazole (MMI) due to potential teratogenic concerns with MMI. This study was to determine the teratogenic potential of MMI and PTU using a validated Xenopus tropicalis embryo model. Embryos were exposed to 1 mM PTU (EC(50)=0.88 mM), 1 mM MMI, or vehicle control (water) from stages 2 to 45. Treated embryos were examined for gross morphological defects, ciliary function, and gene expression by in situ hybridization. Exposure to PTU, but not MMI, led to cardiac and gut looping defects and shortening along the anterior-posterior axis. PTU exposure during gastrulation (stage 8-12.5) was identified as the critical period of exposure leading to left-right (LR) patterning defects. Abnormal cilia polarization, abnormal cilia-driven leftward flow at the gastrocoel roof plate (GRP), and aberrant expression of both Coco and Pitx2c were associated with abnormal LR symmetry observed following PTU exposure. PTU is teratogenic during late blastula, gastrulation, and neurulation; whereas MMI is not. PTU alters ciliary-driven flow and disrupts the normal genetic program involved in LR axis determination. These studies have important implications for women taking PTU during early pregnancy.
Authors:
Nicole R van Veenendaal; Bärbel Ulmer; Marko T Boskovski; Xiefan Fang; Mustafa K Khokha; Christopher C Wendler; Martin Blum; Scott A Rivkees
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-12
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  27     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-01     Completed Date:  2013-03-28     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  684-91     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antithyroid Agents / administration & dosage,  toxicity*
Body Patterning / drug effects*,  genetics
Cilia / drug effects
Digestive System Abnormalities / chemically induced,  embryology
Female
Gene Expression Regulation, Developmental / drug effects
Graves Disease / complications,  drug therapy
Heart Defects, Congenital / chemically induced,  embryology
Humans
Methimazole / administration & dosage,  toxicity
Models, Animal
Pregnancy
Pregnancy Complications / drug therapy
Propylthiouracil / administration & dosage,  toxicity*
Teratogens / toxicity*
Time Factors
Triiodothyronine / pharmacology
Xenopus / embryology*,  genetics
Grant Support
ID/Acronym/Agency:
1R01DE018825/DE/NIDCR NIH HHS; 1R01HD065200/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Antithyroid Agents; 0/Teratogens; 06LU7C9H1V/Triiodothyronine; 554Z48XN5E/Methimazole; 721M9407IY/Propylthiouracil
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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