ToxSci Advance Access originally published online on February 4, 2009
Toxicological Sciences 2009 108(2):427-436; doi:10.1093/toxsci/kfp024
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Bisphenol A Exposure Induces Apoptosis and Upregulation of Fas/FasL and Caspase-3 Expression in the Testes of Mice
* Department of Human Anatomy, Histology and Embryology
Department of Pharmacy, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
Department of Histology and Embryology, Xi'an Medical College, Xi'an, Shaanxi 710021, China
1 To whom correspondence should be addressed at Department of Human Anatomy, Histology and Embryology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Road, Xi'an, Shaanxi 710061, China. Fax: +86-029-82655032. E-mail: songtbao{at}mail.xjtu.edu.cn.
Received December 2, 2008; accepted January 27, 2009
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Abstract |
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There are controversies about adverse effects of bisphenol A (BPA), a ubiquitous xenoestrogen, on reproduction and development of male animals. To understand BPA action and assess its risk more completely, we examined the impact of BPA at high doses on the testes of pubertal male Kunming (China) mice. BPA at 0 (control), 160, 480, and 960 mg/kg/day was given by gavage to mice from postnatal days (PND) 31–44, followed by observation of morphology and detection of apoptosis and expressions of Fas/FasL and active caspase-3 on PND 45, 60, and 90 by terminal deoxynucleotidyl transferase (TdT)–mediated dUTP nick end labeling, immunohistochemistry, and Western blotting. There was no effect of BPA at 160 mg/kg/day, however, at 480 and 960 mg/kg/day there was underdevelopment of testes and disruption of spermatogenesis. There were many apoptotic Leydig and germ cells in the testes with apoptotic indices being significantly increased compared with controls. The expression of Fas and active caspase-3 was localized in the same cell types as apoptosis occurred, and expression levels of Fas, FasL, and active caspase-3 were significantly increased compared with controls. The disturbed spermatogenesis, apoptosis and upregulation of Fas, FasL, and active caspase-3 expression persisted to PND 90. The results suggest that high-dose BPA induces apoptosis of Leydig and germ cells in the mouse testis through the Fas-signaling pathway. Therefore, there is concern about reproductive health for humans occupationally exposed to high levels of BPA.
Key Words: bisphenol A; testis; apoptosis; Fas/FasL; caspase-3; mouse.