Ammonium perfluorooctanoate may cause testosterone reduction by adversely affecting testis in relation to PPARα

Yufei Li, Doni Hikmat Ramdhan, Hisao Naito, Nozomi Yamagishi, Yuki Ito, Yumi Hayashi, Yukie Yanagiba, Ai Okamura, Hazuki Tamada, Frank J. Gonzalez, Tamie Nakajima

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Abstract

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.

Original languageEnglish
Pages (from-to)265-272
Number of pages8
JournalToxicology Letters
Volume205
Issue number3
DOIs
Publication statusPublished - 10-09-2011

All Science Journal Classification (ASJC) codes

  • Toxicology

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    Li, Y., Ramdhan, D. H., Naito, H., Yamagishi, N., Ito, Y., Hayashi, Y., Yanagiba, Y., Okamura, A., Tamada, H., Gonzalez, F. J., & Nakajima, T. (2011). Ammonium perfluorooctanoate may cause testosterone reduction by adversely affecting testis in relation to PPARα. Toxicology Letters, 205(3), 265-272. https://doi.org/10.1016/j.toxlet.2011.06.015