Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
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Styrene Cytotoxicity in Testicular Leydig Cells In Vitro

  • Chung, Jin-Yong (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Park, Ji-Eun (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Kim, Yoon-Jae (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Lee, Seung-Jin (Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology) ;
  • Yu, Wook-Joon (Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology) ;
  • Kim, Jong-Min (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University)
  • Received : 2022.06.10
  • Accepted : 2022.08.22
  • Published : 2022.09.30
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Abstract

Styrene is the precursor of polystyrene. Human exposure to styrene could occur in occupational and residential settings and via food intake. Styrene is metabolized to styrene-7,8-oxide by cytochrome P450 enzyme. In the present study, we investigated the cytotoxicity mediated by styrene and styrene-7,8-oxide in TM3 testicular Leydig cells in vitro. We first monitored the nuclear fragmentation in Leydig cells after exposure to styrene or styrene-7,8-oxide. Hoechst 33258 cell staining showed that styrene exposure in TM3 Leydig cells did not exhibit nuclear fragmentation at any concentration. In contrast, nuclear fragmentation was seen in styrene-7,8-oxide-exposed cells. These results indicate that cytotoxicity-mediated cell death in Leydig cells is more susceptible to styrene-7,8-oxide than to styrene. Following styrene treatment, procaspase-3 and XIAP protein levels did not show significant changes, and cleaved (active) forms of caspase-3 were not detected. Consistent with the western blot results, the active forms of caspase-3 and XIAP proteins were not prominently altered in the cytoplasm of cells treated with styrene. In contrast to styrene, styrene-7,8-oxide induced cell death in an apoptotic fashion, as seen in caspase-3 activation and increased the expression of XIAP proteins. Taken together, the results obtained in this study demonstrate a fundamental idea that Leydig cells are capable of protecting themselves from cytotoxicity-mediated apoptosis as a result of styrene exposure in vitro. It remains unclear whether the steroid-producing function, i.e., steroidogenesis, of Leydig cells is also unaffected by exposure to styrene. Therefore, further studies are needed to elucidate the endocrine disrupting potential of styrene in Leydig cells.

Keywords

Acknowledgement

This work was supported by Korea Environment Industry & Technology Institute (KEITI) through Technology Development Project for Safety Management of Household Chemical Products, funded by Korea Ministry of Environment (MOE) (1485017593).

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