Document Detail


The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero.
MedLine Citation:
PMID:  22682699     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure to exogenous hormones during development can result in permanent health problems. In utero exposure to diethylstilbestrol (DES) is probably the most well documented case in human history. DES, an orally active synthetic estrogen, was believed to prevent adverse pregnancy outcome and thus was routinely given to selected pregnant women from the 1940s to the 1960s. It has been estimated that 5 million pregnant women worldwide were prescribed DES during this period. In the early 1970s, vaginal clear cell adenocarcinomas (CCACs) were diagnosed in daughters whose mother took DES during pregnancy (known as DES daughters). Follow-up studies demonstrated that exposure to DES in utero causes a spectrum of congenital anomalies in female reproductive tracts and CCACs. Among those, cervical and vaginal adenoses are most commonly found, which are believed to be the precursors of CCACs. Transformation related protein 63 (TRP63/p63) marks the cell fate decision of Müllerian duct epithelium (MDE) to become squamous epithelium in the cervix and vagina. DES disrupts the TRP63 expression in mice and induces adenosis lesions in the cervix and vagina. This review describes mouse models that can be used to study the development of DES-induced anomalies, focusing on cervical and vaginal adenoses, and discusses their molecular pathogenesis.
Authors:
Monica M Laronda; Kenji Unno; Lindsey M Butler; Takeshi Kurita
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-06-06
Journal Detail:
Title:  Differentiation; research in biological diversity     Volume:  84     ISSN:  1432-0436     ISO Abbreviation:  Differentiation     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-14     Completed Date:  2012-12-20     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  0401650     Medline TA:  Differentiation     Country:  England    
Other Details:
Languages:  eng     Pagination:  252-60     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
Affiliation:
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma, Clear Cell / chemically induced*,  genetics
Animals
Diethylstilbestrol / adverse effects*
Estrogens, Non-Steroidal / adverse effects*
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Phosphoproteins / genetics
Pregnancy
Prenatal Exposure Delayed Effects*
Trans-Activators / genetics
Uterine Cervical Neoplasms / chemically induced*,  genetics
Vaginal Neoplasms / chemically induced*,  genetics
Grant Support
ID/Acronym/Agency:
R01 CA154358/CA/NCI NIH HHS; R01 CA154358/CA/NCI NIH HHS; R01 HD064402/HD/NICHD NIH HHS; R01HD064402/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Estrogens, Non-Steroidal; 0/Phosphoproteins; 0/Trans-Activators; 0/Trp63 protein, mouse; 56-53-1/Diethylstilbestrol
Comments/Corrections

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