科研之友
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摘要
Perfluorooctanoate, a peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, has the potential to lower testosterone levels as a result of testicular toxicity. To elucidate the mechanism and impact of PPAR alpha on this reproductive toxicity, ammonium pertluorooctanoate (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 (mPPAR alpha), Ppar alpha-null and PPAR alpha-humanized (hPPAR alpha) mice for 6 weeks. Both low- and high-dose APFO significantly reduced plasma testosterone concentrations in mPPAR alpha and hPPAR alpha 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 P450(17 alpha) 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 Ppar alpha-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 mPPAR alpha and hPPAR alpha mice, which may, in part, be related to APFO-induced mitochondrial damage.
- 出版日期2011-9-10
- 单位NIH; 西安交通大学
