Source:http://linkedlifedata.com/resource/pubmed/id/11717140
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2001-11-21
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| pubmed:abstractText |
The present studies were undertaken to determine the testicular cell type(s) affected by the antispermatogenic indenopyridine CDB-4022. At the oral threshold dose (2.5 mg/kg), CDB-4022 induced infertility in all males. CDB-4022 did not alter (P > 0.05) Leydig cell function as assessed by circulating testosterone, seminal vesicle, and ventral prostate weights or body weight gain compared to controls. Conversely, CDB-4022 reduced (P < 0.05) testicular weight, spermatid head counts, and percentage of seminiferous tubules undergoing spermatogenesis. In a second study, adult male rats received a maximally effective oral dose of CDB-4022 (12.5 mg/kg), dipentylphthalate (DPP; 2200 mg/kg; a Sertoli cell toxicant), or vehicle and were necropsied 3, 6, or 12 h after dosing to determine acute effects. Serum inhibin B levels were suppressed (P < 0.05) by 6 h after CDB-4022 or DPP treatment, but epididymal androgen-binding protein (ABP) levels were not altered (P > 0.05), compared to controls. CDB-4022 and DPP increased (P < 0.05) the percentage of tubules with apoptotic germ cells, particularly differentiating spermatogonia and spermatocytes, by 12 h after dosing. Microscopic examination of the testis indicated a greater degree of vacuolation in Sertoli cells and initial signs of apical germ cell sloughing/shedding by 3 or 12 h after CDB-4022 or DPP treatment, respectively. In a third study, prepubertal male rats were treated with vehicle, 12.5 mg/kg of CDB-4022, or 2200 mg/kg of DPP, and the efferent ducts of the right testis were ligated 23 h before necropsy. Seminiferous tubule fluid secretion (difference in weight of testes), serum inhibin B levels, and ABP levels in the unligated epididymis were reduced (P < 0.05) at 24 and 48 h after dosing in CDB-4022- and DPP-treated rats compared to controls. Collectively, these data suggest that CDB-4022 disrupts spermatogenesis by inducing apoptosis in early stage germ cells via a direct action on the Sertoli cell.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Androgen-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Antispermatogenic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CDB 4022,
http://linkedlifedata.com/resource/pubmed/chemical/Indenes,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibins,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/inhibin B
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
|
| pubmed:issn |
0006-3363
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
65
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1771-9
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11717140-Androgen-Binding Protein,
pubmed-meshheading:11717140-Animals,
pubmed-meshheading:11717140-Antispermatogenic Agents,
pubmed-meshheading:11717140-Apoptosis,
pubmed-meshheading:11717140-Epididymis,
pubmed-meshheading:11717140-Female,
pubmed-meshheading:11717140-Fertility,
pubmed-meshheading:11717140-Indenes,
pubmed-meshheading:11717140-Inhibins,
pubmed-meshheading:11717140-Leydig Cells,
pubmed-meshheading:11717140-Male,
pubmed-meshheading:11717140-Organ Size,
pubmed-meshheading:11717140-Piperidines,
pubmed-meshheading:11717140-Rats,
pubmed-meshheading:11717140-Rats, Sprague-Dawley,
pubmed-meshheading:11717140-Seminiferous Tubules,
pubmed-meshheading:11717140-Sertoli Cells,
pubmed-meshheading:11717140-Sperm Count,
pubmed-meshheading:11717140-Spermatids,
pubmed-meshheading:11717140-Spermatogenesis,
pubmed-meshheading:11717140-Spermatogonia,
pubmed-meshheading:11717140-Spermatozoa,
pubmed-meshheading:11717140-Testis,
pubmed-meshheading:11717140-Vacuoles
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| pubmed:year |
2001
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| pubmed:articleTitle |
Disruption of spermatogenesis and Sertoli cell structure and function by the indenopyridine CDB-4022 in rats.
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| pubmed:affiliation |
BIOQUAL, Inc., Rockville, Maryland 20850, USA. sahild@compuserve.com
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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