کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2599868 1133233 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ammonium perfluorooctanoate may cause testosterone reduction by adversely affecting testis in relation to PPARα
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Ammonium perfluorooctanoate may cause testosterone reduction by adversely affecting testis in relation to PPARα
چکیده انگلیسی

Perfluorooctanoate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, has the potential to lower testosterone levels as a result of testicular toxicity. To elucidate the mechanism and impact of PPARα on this reproductive toxicity, ammonium perfluorooctanoate (APFO) at doses of 0, 1.0 (low) mg/kg/day, or 5.0 (high) mg/kg/day was orally given daily to 129/sv wild-type (mPPARα), Pparα-null and PPARα-humanized (hPPARα) mice for 6 weeks. Both low- and high-dose APFO significantly reduced plasma testosterone concentrations in mPPARα and hPPARα mice, respectively. These decreases may, in part, be associated with decreased expression of mitochondrial cytochrome P450 side-chain cleavage enzyme, steroidogenic acute regulatory protein or peripheral benzodiazepine receptor as well as microsomal cytochrome P45017α involved in the steroidogenesis. Additionally, both doses increased abnormalities in sperm morphology and vacuolated cells in the seminiferous tubules of both mouse lines. In contrast, APFO caused only a marginal effect either on the testosterone synthesis system or sperm and testis morphology in Pparα-null mice. These results suggest that APFO may disrupt testosterone biosynthesis by lowering the delivery of cholesterol into the mitochondria and decreasing the conversion of cholesterol to pregnenolone and androstandione in the testis of mPPARα and hPPARα mice, which may, in part, be related to APFO-induced mitochondrial damage.


• Impact of PPARα in the reproductive toxicity of APFO using three genotyped mice.
• APFO given orally for 6 weeks reduced plasma testosterone of mPPARα and hPPARα mice.
• APFO caused only a marginal effect on Pparα-null mice.
• APFO may suppress testosterone syntheses through hepatic mouse and human PPARα.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 205, Issue 3, 10 September 2011, Pages 265–272
نویسندگان
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