| Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate. | |
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MedLine Citation:
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PMID: 16466534 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Foetal exposure of male rats to di(n-butyl) phthalate (DBP) induces testicular changes similar to testicular dysgenesis syndrome in humans, including the formation of focal 'dysgenetic areas' within post-natal testes, surrounded by otherwise normal tubules exhibiting complete spermatogenesis. We hypothesize that these dysgenetic areas form when Sertoli (and other) cells are 'trapped' during the abnormal formation of large Leydig cell (LC) clusters in foetal life and by post-natal day (d) 4 these groups of intermingled cells attempt to form seminiferous tubules. It is likely that the malformed tubules resulting correspond to the dysgenetic areas evident in later life. This also provides a plausible explanation for the occurrence of LCs within seminiferous cords/tubules in or bordering the dysgenetic areas. In our previous studies intratubular LCs (ITLCs) were identified by immunostaining for 3beta-hydroxysteroid dehydrogenase (3beta-HSD), the definitive LC cytoplasmic marker. However, the possibility remained that the 'presumptive' ITLCs were in fact Sertoli cells that had aberrantly gained the ability to express 3beta-HSD. Therefore, the aim of the present study was to fully characterize the ITLCs induced by in utero DBP exposure in d25 rats using a number of LC- (3beta-HSD, P450 side-chain cleavage enzyme, insulin-like factor 3, oestrogen receptor alpha) and Sertoli cell- (vimentin, Wilm's tumour-1) specific markers. Our results show that ITLCs express all four LC-specific markers but do not express either of the Sertoli cell markers. It is therefore concluded that the ITLCs are bona fide LCs that are abnormally located within the seminiferous tubules of DBP-exposed rats in post-natal life. |
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Authors:
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I Kim Mahood; Chris McKinnell; Marion Walker; Nina Hallmark; Hayley Scott; Jane S Fisher; Ana Rivas; Stefan Hartung; Richard Ivell; J Ian Mason; Richard M Sharpe |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of andrology Volume: 29 ISSN: 0105-6263 ISO Abbreviation: Int. J. Androl. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-02-09 Completed Date: 2006-04-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8000141 Medline TA: Int J Androl Country: England |
Other Details:
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Languages: eng Pagination: 148-54; discussion 181-5 Citation Subset: IM |
Affiliation:
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Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh, UK. k.mahood@hrsu.mrc.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Androgen Antagonists
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administration & dosage,
toxicity* Animals Dibutyl Phthalate / administration & dosage, toxicity* Disease Models, Animal* Female Humans Leydig Cells / pathology Male Maternal Exposure / adverse effects* Pregnancy Prenatal Exposure Delayed Effects* Rats Rats, Wistar Sertoli Cells / pathology Testis / abnormalities*, drug effects, pathology |
| Chemical | |
Reg. No./Substance:
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0/Androgen Antagonists; 84-74-2/Dibutyl Phthalate |
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