Skip Navigation



ToxSci Advance Access published online on December 29, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfi071
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
85/1/675    most recent
kfi071v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Fukushima, T.
Right arrow Articles by Horii, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fukushima, T.
Right arrow Articles by Horii, I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences © Society of Toxicology 2004; all rights reserved.
Received November 1, 2004
Accepted December 20, 2004

Reproductive and Developmental Toxicology

Effects of sulfasalazine on sperm acrosome reaction and gene expression in the male reproductive organs of rats

Tamio Fukushima 1*, Masashi Kato 2, Tetsuya Adachi 3, Yoshimasa Hamada 2, Masao Horimoto 2, Masatoshi Komiyama 4, Chisato Mori 5, and Ikuo Horii 2

1 Worldwide Safety Sciences, Nagoya Laboratories, Pfizer Japan Inc., 5-2, Taketoyo, Aichi 470-2393, Japan; Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chiba 260-8670, Japan
2 Worldwide Safety Sciences, Nagoya Laboratories, Pfizer Japan Inc., 5-2, Taketoyo, Aichi 470-2393, Japan
3 Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
4 Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chiba 260-8670, Japan; Center for Environment, Health and Field Sciences, Chiba University, Kashiwa, 227-0882, Japan
5 Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chiba 260-8670, Japan

* To whom correspondence should be addressed.
Tamio Fukushima, E-mail: Tamio.Fukushima{at}japan.pfizer.com


  Abstract

Sulfasalazine (SASP) has been reported to depress the fertility in men and experimental male animals, but the fundamental mechanisms of infertility caused by SASP are still unknown. This study was designed to investigate the mechanisms of infertility in rats treated with SASP at a dose of 600 mg/kg for 28 days, including monitoring of sperm motility using computer associated sperm analysis system and acrosome reaction by FITC-concanavalin A lectin staining. The sperm motility and acrosome reaction, which are important for fertilization, were significantly reduced by SASP. Furthermore, to investigate the molecular mechanisms of infertility induced by SASP, mRNA expression analysis in the testes was performed using cDNA microarray as a first screening. It was revealed that CD59, which is located on the acrosomal membrane and is known to be important for the reproductive function of sperm, was affected in the testes; this was also confirmed by real-time PCR analysis, but the spermatogenesis-related genes examined in this study were not affected. Therefore, we focused on CD59 and two other acrosome membrane related-genes: MCP and DAF. CD59, MCP and DAF in the epididymides of SASP-treated rats were significantly decreased as assessed by real-time RT-PCR analysis and additionally, the expression of CD59 protein was found to be decreased by Western blotting. These results allowed us to hypothesize that the suppression of epididymal acrosomal membrane proteins synthesis with their consequent reduced incorporation to the sperm membrane leads to a depressed sperm motility and acrosome reaction, and thereby leads to infertility in SASP treated male rats

Keywords: sulfasalazine; acrosome reaction; CD59; mRNA expression.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.