Document Detail


Do phthalates affect steroidogenesis by the human fetal testis? Exposure of human fetal testis xenografts to di-n-butyl phthalate.
MedLine Citation:
PMID:  22238399     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Phthalates are ubiquitous environmental chemicals. Fetal exposure to certain phthalates [e.g. di-n-butyl phthalate (DBP)] causes masculinization disorders in rats, raising concern for similar effects in humans. We investigated whether DBP exposure impairs steroidogenesis by the human fetal testis.
OBJECTIVE: The aim of the study was to determine effects of DBP exposure on testosterone production by normally growing human fetal testis xenografts.
DESIGN: Human fetal testes (14-20 wk gestation; n=12) were xenografted into castrate male nude mice that were treated for 4-21 d with vehicle, or 500 mg/kg·d DBP, or monobutyl phthalate (active metabolite of DBP); all mice were treated with human chorionic gonadotropin to mimic normal human pregnancy. Rat fetal testis xenografts were exposed for 4 d to DBP as a positive control.
MAIN OUTCOME MEASURES: Testosterone production was assessed by measuring host serum testosterone and seminal vesicle (SV) weights at termination, plus testis gene expression (rats).
RESULTS: Human fetal testis xenografts showed similar survival (∼80%) and total graft weight (8.6 vs. 10.1 mg) in vehicle and DBP-exposed hosts, respectively. Serum testosterone (0.56 vs. 0.64 ng/ml; P>0.05) and SV weight (67.2 vs. 81.9 mg; P>0.05) also did not differ. Exposure to monobutyl phthalate gave similar results. In contrast, exposure of rat fetal xenografts to DBP significantly reduced SV weight and testis Cyp11a1/StAR mRNA expression and lowered testosterone levels, confirming that DBP exposure can inhibit steroidogenesis in xenografts, further validating the negative findings on testosterone production in the human.
CONCLUSIONS: Exposure of human fetal testes to DBP is unlikely to impair testosterone production as it does in rats. This has important safety and regulatory implications.
Authors:
R T Mitchell; A J Childs; R A Anderson; S van den Driesche; P T K Saunders; C McKinnell; W H B Wallace; C J H Kelnar; R M Sharpe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-11
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  97     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-06     Completed Date:  2012-07-06     Revised Date:  2014-11-05    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E341-8     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Dibutyl Phthalate / pharmacology*
Fetus
Humans
Male
Mice
Mice, Nude
Testis / drug effects*,  embryology,  metabolism
Testosterone / biosynthesis*
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
G1002033//Medical Research Council; G1100357//Medical Research Council; G1100358//Medical Research Council; G33253//Medical Research Council
Chemical
Reg. No./Substance:
2286E5R2KE/Dibutyl Phthalate; 3XMK78S47O/Testosterone

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


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