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J Clin Endocrinol Metab. 2012 Mar;97(3):E341-8. doi: 10.1210/jc.2011-2411. Epub 2012 Jan 11.

Do phthalates affect steroidogenesis by the human fetal testis? Exposure of human fetal testis xenografts to di-n-butyl phthalate.

Author information

1
Medical Research Council/University of Edinburgh Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh Royal Hospital for Sick Children, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom. Rod.Mitchell@ed.ac.uk

Abstract

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.

PMID:
22238399
DOI:
10.1210/jc.2011-2411
[Indexed for MEDLINE]

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