| Role of androgens in fetal testis development and dysgenesis. | |
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MedLine Citation:
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PMID: 17289843 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-02-08 |
Journal Detail:
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Title: Endocrinology Volume: 148 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-04-20 Completed Date: 2007-06-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 2027-36 Citation Subset: AIM; IM |
Affiliation:
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Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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9,10-Dimethyl-1,2-benzanthracene
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pharmacology Androgen Antagonists / pharmacology Animals Body Weight Carcinogens / pharmacology Dibutyl Phthalate / pharmacology Female Feminization / pathology, physiopathology Flutamide / pharmacology Giant Cells / pathology Gonadal Dysgenesis / pathology*, physiopathology* Leydig Cells / pathology Male Mice Mice, Knockout Organ Size Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Receptors, Androgen / genetics Sertoli Cells / pathology Testis / abnormalities*, pathology Testosterone / deficiency*, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Androgen Antagonists; 0/Carcinogens; 0/Receptors, Androgen; 13311-84-7/Flutamide; 57-97-6/9,10-Dimethyl-1,2-benzanthracene; 58-22-0/Testosterone; 84-74-2/Dibutyl Phthalate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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