Original Research Article
Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3- and caspase-9-dependent mitochondrial signaling pathway
Version of Record online: 23 JAN 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 5, pages 1814–1820, May 2012
How to Cite
Zhu, L., Yuan, H., Guo, C., Lu, Y., Deng, S., Yang, Y., Wei, Q., Wen, L. and He, Z. (2012), Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3- and caspase-9-dependent mitochondrial signaling pathway. J. Cell. Physiol., 227: 1814–1820. doi: 10.1002/jcp.22906
- Issue online: 23 JAN 2012
- Version of Record online: 23 JAN 2012
- Accepted manuscript online: 5 JUL 2011 10:28AM EST
- Manuscript Accepted: 16 JUN 2011
- Manuscript Received: 14 MAR 2011
- Department of Education of Hunan Province, China; Shanghai Pujiang Program; Focus Construction Subject of Shanghai Education Department; Shanghai Key Laboratory of Gynecologic Oncology. Grant Number: 03A020
Zearalenone is a mycotoxin produced mainly by Fusarium. There are numerous incidences of mycotoxicosis in laboratory and domestic animals, especially in pigs. However, little is known about molecular mechanisms of zearalenone toxicity. Granulosa cells are the maximal cell population in follicles, and they play an essential role in the development and maturation of follicles. The objective of this study was to explore the effect of zearalenone at high concentrations on proliferation and apoptosis of porcine granulosa cells and uncover signaling pathway underlying the cytotoxicity of zearalenone. We found that zearalenone reduced the proliferation of porcine granulosa cells in a dose-dependent manner as shown by the MTT assay and zearalenone resulted in an obvious apoptosis and necrosis in porcine granulosa cells as determined by the TUNEL analysis and flow cytometry. In addition, TUNEL assay with caspase inhibitors showed that zearalenone triggered a caspase-3- and caspase-9-dependent apoptotic process in porcine granulosa cells. Fluorescence spectrophotometer displayed that zearalenone led to a loss of mitochondrial transmembrane potential of porcine granulosa cells but enhanced reactive oxygen species (ROS) levels of the cells. Notably, Western blots revealed that caspase-3 and caspase-9 were activated by zearalenone in porcine granulosa cells. Collectively, our results suggest that zearalenone induces apoptosis and necrosis of porcine granulosa cells in a dose-dependent manner via a caspase-3- and caspase-9-dependent mitochondrial pathway. This study thus offers a novel insight into molecular mechanisms by which zearalenone has adverse cytotoxicity on reproduction. J. Cell. Physiol. 227: 1814–1820, 2012. © 2011 Wiley Periodicals, Inc.