| Do Phthalates Affect Steroidogenesis by the Human Fetal Testis? Exposure of Human Fetal Testis Xenografts to Di-n-Butyl Phthalate. | |
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MedLine Citation:
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PMID: 22238399 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-1-11 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: - ISSN: 1945-7197 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Medical Research Council/University of Edinburgh Centre for Reproductive Health (R.T.M., A.J.C., R.A.A., S.v.d.D., P.T.K.S., C.M., R.M.S.), The Queen's Medical Research Institute, Edinburgh EH16 4TJ, Scotland, United Kingdom; and Edinburgh Royal Hospital for Sick Children (R.T.M., W.H.B.W., C.J.H.K.), Edinburgh EH9 1LF, Scotland, United Kingdom. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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