Document Detail

Role of androgens in fetal testis development and dysgenesis.
MedLine Citation:
PMID:  17289843     Owner:  NLM     Status:  MEDLINE    
This study sought to establish whether reduced androgen levels/action in the fetal rat testis induced by di(n-butyl) phthalate (DBP) contributes to dysgenetic features, namely reduced Sertoli cell number, occurrence of multinucleated gonocytes (MNG), and Leydig cell aggregation. Pregnant rats were administered treatments or cotreatments designed to manipulate testosterone levels [DBP, testosterone propionate (TP)] or action [flutamide, 7,12-dimethyl-benz[a]anthracene (DMBA)]. The aforementioned end points were analyzed and related to intratesticular testosterone (ITT) levels and peripheral androgen action (anogenital distance). Dysgenetic features were also evaluated in mice with inactivation of the androgen receptor (testicular feminized or ARKO mice). Exposure to DBP alone, or combined with flutamide, DMBA, or TP, resulted in reduced Sertoli cell number and ITT levels, as did exposure to TP alone; coadministration of DBP + TP caused the most severe reduction in both parameters. A positive correlation between ITT levels and Sertoli cell number was found (r = 0.791; P = 0.019). Similarly, exposure to DBP alone, or as a cotreatment, significantly increased occurrence of MNG and Leydig cell aggregation, and these were negatively correlated with ITT levels. Exposure to flutamide or DMBA alone had no significant effect on these dysgenetic end points. These findings suggest that reduced ITT decreases fetal Sertoli cell numbers and might be involved in Leydig cell aggregation and MNG. However, of these three end points, only Sertoli cell number was affected significantly in ARKO/testicular feminized mice with absent androgen action. Therefore, induction of MNG and Leydig cell aggregation might result from DBP-induced effects other than suppression of ITT levels.
Hayley M Scott; Gary R Hutchison; I Kim Mahood; Nina Hallmark; Michelle Welsh; Karel De Gendt; Guido Verhoeven; Peter O'Shaughnessy; Richard M Sharpe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-02-08
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-20     Completed Date:  2007-06-04     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2027-36     Citation Subset:  AIM; IM    
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MeSH Terms
9,10-Dimethyl-1,2-benzanthracene / pharmacology
Androgen Antagonists / pharmacology
Body Weight
Carcinogens / pharmacology
Dibutyl Phthalate / pharmacology
Feminization / pathology,  physiopathology
Flutamide / pharmacology
Giant Cells / pathology
Gonadal Dysgenesis / pathology*,  physiopathology*
Leydig Cells / pathology
Mice, Knockout
Organ Size
Prenatal Exposure Delayed Effects
Rats, Wistar
Receptors, Androgen / genetics
Sertoli Cells / pathology
Testis / abnormalities*,  pathology
Testosterone / deficiency*,  physiology*
Grant Support
MC_U127684422//Medical Research Council; MC_U127685841//Medical Research Council
Reg. No./Substance:
0/Androgen Antagonists; 0/Carcinogens; 0/Receptors, Androgen; 2286E5R2KE/Dibutyl Phthalate; 3XMK78S47O/Testosterone; 57-97-6/9,10-Dimethyl-1,2-benzanthracene; 76W6J0943E/Flutamide

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