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ToxSci Advance Access published online on March 30, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm070
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Alterations in Gene Expression and Testosterone Synthesis in the Testes of Male Rats Exposed to Perfluorododecanoic Acid

Zhimin Shi*,{dagger}, Hongxia Zhang*, Yang Liu*, Muqi Xu* and Jiayin Dai*,{ddagger}

* Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100080, China {dagger} Graduate School of the Chinese Academy of Sciences, Beijing, 100080, China

{ddagger} Corresponding author: Jiayin Dai, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100080, China, Tel.: +86-10-64807185, Fax: +86-10-64807099, E-mail: daijy{at}ioz.ac.cn

Received February 14, 2007; revision received March 13, 2007; accepted March 13, 2007


  Abstract

Perfluorododecanoic acid (PFDoA, C12), a synthetic perfluorinated chemical containing twelve carbons, has broad industrial applications and has been detected in sera from humans and other animals; however, few reports have addressed the effects of PFDoA exposure on male reproduction. In the present study, the effects of PFDoA exposure on testes ultrastructure, testosterone levels, and steroidogenic gene expression were investigated. Male rats were orally dosed for fourteen days with 1, 5, or 10 mg PFDoA/kg/day or with vehicle. Absolute testis weight was diminished at the highest dose while relative testes weight was markedly increased at doses of 5 and 10 mg/kg/day. Total serum cholesterol levels were significantly increased at the highest dose. While luteinizing hormone (LH) was significantly decreased at the highest dose, testosterone was markedly decreased at doses of 5 and 10 mg PFDoA/kg/day. Serum levels of follicle stimulating hormone (FSH) were not significantly affected by PFDoA, and estradiol levels were markedly decreased only at 5mg/kg/day. Leydig cells, Sertoli cells, and spermatogenic cells from rats that received 5 or 10 mg PFDoA/kg/day exhibited apoptotic features including dense irregular nuclei, condensed chromatin, ill-defined nuclear membranes, and abnormal mitochondria. PFDoA exposure resulted in significant declines in mRNA expression of several genes involved in cholesterol transport and steroid biosynthesis at doses of 5 and 10 mg PFDoA/kg/day while the gene expression of luteinizing hormone receptor (LHR) and aromatase was not significantly changed. Our results demonstrate that PFDoA affects the reproduction function of male rats via alterations in steroidogenesis genes, testosterone levels, and testes ultrastructure.

Key Words: perfluorododecanoic acid; testis; testosterone; ultrastructure; steroidogenesis gene.


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