Document Detail

Proposed mode of action for in utero effects of some phthalate esters on the developing male reproductive tract.
MedLine Citation:
PMID:  16698716     Owner:  NLM     Status:  MEDLINE    
Phthalate esters containing a straight-chain backbone of 4-6 carbons have demonstrated testicular toxicity and infertility in adult and pre-adolescent rats, mice, hamsters, and ferrets. In recent years, these same phthalates have been shown to interfere with the normal development of the male reproductive tract in rodents and rabbits. The review presented here summarizes studies that provide evidence of a mode of action for these effects. The data indicate that C4-C6 phthalate esters inhibit processes in the Leydig cell, such as the synthesis of testosterone (T) and production of insulin-like factor 3 (insl3), both of which are required for normal development of male genitalia. A proposed secondary effect of reduced androgen production is on Sertoli cells, resulting in failure to proliferate and interference with cell-cell communication (gap-junction intracellular communication) leading to the development of large multinucleate gonocytes. The possibility that phthalates act directly on the Sertoli cells to interfere with intracellular communication is not excluded. The strength, consistency, and plausibility of the proposed mode of action and alternate modes of action are discussed.
Raymond M David
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Toxicologic pathology     Volume:  34     ISSN:  0192-6233     ISO Abbreviation:  Toxicol Pathol     Publication Date:  2006  
Date Detail:
Created Date:  2006-05-15     Completed Date:  2006-08-18     Revised Date:  2009-07-01    
Medline Journal Info:
Nlm Unique ID:  7905907     Medline TA:  Toxicol Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  209-19     Citation Subset:  IM    
K&D Scientific Consulting, Inc., Pittsford, New York 14534, USA.
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MeSH Terms
Esters / toxicity
Genitalia, Male / drug effects*,  pathology
Leydig Cells / drug effects,  metabolism
Maternal Exposure*
Phthalic Acids / metabolism,  toxicity*
Sertoli Cells / drug effects,  metabolism
Testosterone / metabolism
Reg. No./Substance:
0/Esters; 0/Phthalic Acids; 58-22-0/Testosterone; 88-99-3/phthalic acid

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

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