TiO2 nanoparticles-induced apoptosis of primary cultured Sertoli cells of mice
Corresponding Author
Fashui Hong
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
*These authors contributed equally to this work.
Correspondence to: F. Hong; e-mail: [email protected]Search for more papers by this authorXiaoyang Zhao
Medical College of Soochow University, Suzhou, People's Republic of China
*These authors contributed equally to this work.
Search for more papers by this authorMing Chen
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
*These authors contributed equally to this work.
Search for more papers by this authorYingjun Zhou
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
Search for more papers by this authorYuguan Ze
Medical College of Soochow University, Suzhou, People's Republic of China
Search for more papers by this authorLing Wang
Library of Soochow University, Suzhou, People's Republic of China
Search for more papers by this authorYajing Wang
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
Search for more papers by this authorYushuang Ge
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
Search for more papers by this authorQi Zhang
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
Search for more papers by this authorLingqun Ye
Medical College of Soochow University, Suzhou, People's Republic of China
Search for more papers by this authorCorresponding Author
Fashui Hong
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
*These authors contributed equally to this work.
Correspondence to: F. Hong; e-mail: [email protected]Search for more papers by this authorXiaoyang Zhao
Medical College of Soochow University, Suzhou, People's Republic of China
*These authors contributed equally to this work.
Search for more papers by this authorMing Chen
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
*These authors contributed equally to this work.
Search for more papers by this authorYingjun Zhou
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
Search for more papers by this authorYuguan Ze
Medical College of Soochow University, Suzhou, People's Republic of China
Search for more papers by this authorLing Wang
Library of Soochow University, Suzhou, People's Republic of China
Search for more papers by this authorYajing Wang
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
Search for more papers by this authorYushuang Ge
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
Search for more papers by this authorQi Zhang
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, People's Republic of China
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, People's Republic of China
School of Life Sciences, Huaiyin Normal University, Huaian, People's Republic of China
Search for more papers by this authorLingqun Ye
Medical College of Soochow University, Suzhou, People's Republic of China
Search for more papers by this authorAbstract
Titanium dioxide nanoparticles (TiO2 NPs), as largest production and use of nanomaterials, have been demonstrated to have a potential toxicity on reproductive system. However, the mechanism underlying male reproductive toxicity of TiO2 NPs remains limited. Thus, our study was designed to examine the cellular viability, apoptosis, oxidative stress, antioxidant capacity, and expression of apoptotic cytokines in primary cultured Sertoli cells isolated from mice under TiO2 NPs exposure. Results showed that TiO2 NPs exposure from 5 to 30 μg/mL resulted in reduction of cell viability, lactate dehydrogenase release, and induction of apoptosis or death on Sertoli cells. TiO2 NPs could migrate to Sertoli cells, which induced mitochondria-mediated or endoplasmic-reticulum-mediated apoptotic changes including elevation in reactive oxygen species (ROS) generation and reductions in superoxide dismutase, catalase, and glutathione peroxidase activities, decreases in mitochondrial membrane potential (ΔΨm), and releases of cytochrome c into the cytosol. In addition, upregulation of cytochrome c, Bax, caspase-3, glucose-regulated protein 78, and C/EBP homologous protein and caspase-12 protein expression, and downregulation of bcl-2 protein expression in primary cultured Sertoli cells induced by TiO2 NPs treatment. All of the results suggested that ROS generation may play a critical role in the initiation of TiO2 NPs-induced apoptosis by mediation of the disruption of ΔΨm, the cytochrome c release, and further the activation of caspase cascade and unfolded protein response signaling pathway. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 124–135, 2016.
REFERENCES
- 1 Robichaud CO, Uyar AE, Darby MR, Zucker LG, Wiesner MR. Estimates of upper bounds and trends in nano-TiO2 production as a basis for exposure assessment. Environ Sci Technol 2009; 43: 4227–4233.
- 2 Weir A, Westerhoff P, Fabricius L, Hristovski K, von Goetz N. Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol 2012; 46: 2242–2250.
- 3 Iavicoli I, Leso V, Bergamaschi A. Toxicological effects of titanium dioxide nanoparticles: a review of in vivo studies. J Nanomater 2012; 1–36.
- 4 La Z, Yang WX. Nanoparticles and spermatogenesis: how do nanoparticles affect spermatogenesis and penetrate the blood–testis barrier. Nanomedicine (Lond) 2012; 7: 579–596.
- 5 Shi HB, Magaye R, Castranova V, Zhao JS. Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol 2013; 10: 15
- 6 Guo LL, Liu XH, Qin DX, Gao L, Zhang HM, Liu JY, Cui YG. Effects of nanosized titanium dioxide on the reproductive system of male mice. Zhonghua Nan Ke Xue 2009; 15: 517–522. (in Chinese)
- 7 Wang Y, Wang Y, Ge SQ, Yang HL, Zhang WW, Cao HC, Chen ZG. Effects of nanosized titanium dioxide on reproductive system in male mice. J Environ Health 2011; 28: 262–264. (in Chinese)
- 8 Gao GD, Ze YG, Li B, Zhao XY, Liu XR, Sheng L, Hu RP, Gui SX, Sang XZ, Sun QQ, Cheng J, Cheng Z, Wang L, Tang M, Hong FS. The ovarian dysfunction and its gene-expressed characteristics of female mice caused by long-term exposure to titanium dioxide nanoparticles. J Hazard Mater 2012; 243: 19–27.
- 9 Gao GD, Ze YG, Zhao XY, Sang XZ, Zheng L, Ze X, Gui SX, Sheng L, Sun QQ, Hong J, Yu XH, Wang L, Hong FS, Zhang XG. Titanium dioxide nanoparticle-induced testicular damage, spermatogenesis suppression, and gene expression alterations in male mice. J Hazard Mater 2013; 258: 133–143.
- 10 Zhao XY, Ze YG, Gao GD, Sang XZ, Li B, Gui SX, Sheng L, Sun QQ, Cheng J, Cheng Z, Hu RP, Wang L, Hong FS. Nanosized TiO2-induced reproductive system dysfunction and its mechanism in female mice. PLoS One 2013; 8: e59378
- 11 Meena R, Kajal K, Paulraj R. Cytotoxic and genotoxic effects of titanium dioxide nanoparticles in testicular cells of male Wistar rat. Appl Biochem Biotechnol 2015; 175: 825–840.
- 12 Komatsu T, Tabata M, Kubo-Irie M, Shimizu T, Suzuki KI, Nihei Y, Takeda K. The effects of nanoparticles on mouse testis Leydig cells in vitro. Toxicol In Vitro 2008; 22: 1825–1831.
- 13 Hou J, Wan XY, Wang F, Xu GF, Liu Z, Zhang TB. Effects of titanium dioxide nanoparticles on development and maturation of rat preantral follicle in vitro. Acad J Second Military Med Univ 2009; 30: 869–873. (in Chinese)
- 14 Suzuki H, Toyooka T, Ibuki Y. Simple and easy method to evaluate uptake potential of nanoparticles in mammalian cells using a flow cytometric light scatter analysis. Environ Sci Technol 2007; 41: 3018–3024.
- 15 Di Virgilio AL, Reigosa M, Arnal PM, Fernández Lorenzo de Mele M. Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells. J Hazard Mater 2010; 177: 711–718.
- 16 Takeda K, Suzuki K, Ishihara A, Kubo-Irie M, Fujimoto R, Tabata M, Oshio S, Nihei Y, Ihara T, Sugamata M. Nanoparticles transferred from pregnant mice to their offspring can damage the genital and cranial nerve systems. J Health 2009; 55: 95–102.
- 17 Griswold MD. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol 1998; 9: 411–416.
- 18 Griswold MD. Interactions between germ cells and Sertoli cells in the testis. Biol Reprod 1995; 52: 211–216.
- 19 Meehan T, Schlatt S, O'Bryan MK, de Kretser DM, Loveland KL. Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH. Dev Biol 2000; 220: 225–637.
- 20 Amann RP. The male rabbit. IV. Quantitative testicular histology and comparisons between daily sperm production as determined histologically and daily sperm output. Fertil Steril 1970; 21: 662–672.
- 21 Yang P, Lu C, Hua N, Du Y. Titanium dioxide nanoparticles co-doped with Fe3+ and Eu3+ ions for photocatalysis. Mater Lett 2002; 57: 794–801.
- 22 Hu RP, Zheng L, Zhang T, Cui YL, Gao GD, Cheng Z, Chen J, Tang M, Hong FS. Molecular mechanism of hippocampal apoptosis of mice following exposure to titanium dioxide nanoparticles. J Hazard Mater 2011; 191: 32–40.
- 23 Gassei K, Schlatt S, Ehmcke J. De novo morphogenesis of seminiferous tubules from dissociated immature rat testicular cells in xenografts. J Androl 2006; 27: 611–618.
- 24 Asatiani N, Sapojnikova N, Abuladze M, Kartvelishvili T, Kulikova N, Kiziria E, Namchevadze E, Holman HY. Effects of Cr(VI) long-term and low-dose action on mammalian antioxidant enzymes (an in vitro study). J Inorg Biochem 2004; 98: 490–496.
- 25 Li XB, Xu SQ, Zhang ZR, Hermann JS. Apoptosis induced by titanium dioxide nanoparticles in cultured murine microglia N9 cells. Chin Sci Bull 2009; 54: 3830–3836.
- 26 Reers M, Smith TW, Chen LB. J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential. Biochemistry 1991; 30: 4480–4486.
- 27 Yu X, Sidhu JS, Hong S, Faustman EM. Essential role of extracellular matrix (ECM) overlay in establishing the functional integrity of primary neonatal rat Sertoli cell/gonocyte co-cultures: An improved in vitro model for assessment of male reproductive toxicity. Toxicol Sci 2005; 84: 378–393.
- 28 Iijima T. Mitochondrial membrane potential and ischemic neuronal death. Neurosci Res 2006; 55: 234–243.
- 29 Iijima T, Mishima T, Tohyama M, Akaqawa K, Iwao Y. Mitochondrial membrane potential and intracellular ATP content after transient experimental ischemia in the cultured hippocampal neuron. Neurochem Int 2003; 43: 263–269.
- 30 Szeto HH. Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS J 2006; 8: E521–E531.
- 31 Rizzuto R, Pinton P, Ferrari D, Chami M, Szabadkai G, Magalhaes PJ, Di Virgilio F, Pozzan T. Calcium and apoptosis: facts and hypotheses. Oncogene 2003; 22: 8619–8627.
- 32 Simon HU, Yehia AH, Schaffer FL. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 2000; 5: 415–418.
- 33 Yao JC, Jiang ZZ, Duan WG, Huang JF, Zhang LY, Hu L, He L, Fu LI, Xiao YI, Shu B, Liu CH. Involvement of mitochondrial pathway in triptolide-induced cytotoxicity in human normal liver L-02 cells. Biol Pharm Bull 2008; 31: 592–597.
- 34 Korsmeyer SJ, Yin XM, Oltvai ZN, Veis-Novack DJ, Linette GP. Reactive oxygen species and the regulation of cell death by the Bcl-2 gene family. Biochim Biophys Acta 1995; 1271: 63–66.
- 35 Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 1995; 80: 285–291.
- 36 Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 1998; 281: 1322–1326.
- 37 Laakso MP, Lehtovirta M, Partanen K, Riekkinen PJ, Soininen H. Hippocampus in Alzheimer's disease: A 3-year follow-up MRI study. Biol Psychiatr 2006; 6: 557–561.
- 38 Kosuge Y, Sakikubo T, Ishige K, Ito Y. Comparative study of endoplasmic reticulum stress-induced neuronal death in rat cultured hippocampal and cerebellar granule neurons. Neurochem Int 2006; 49: 285–293.
- 39 Gorman AM, Healy SJM, Jäger R, Samali A. Stress management at the ER: Regulators of ER stress-induced apoptosis. Pharmacol Therap 2012; 134: 306–316.
- 40 Wang JX, Chen CY, Liu Y, Jiao F, Li W, Lao F, Li YF, Li B, Ge CC, Zhou GQ, Gao YX, Zhao YL, Chai ZF. Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases. Toxicol Lett 2008; 183: 72–80.
- 41 Wang JX, Liu Y, Jiao F, Lao F, Li W, Gu YQ, Li YF, Ge CC, Zhou GQ, Li B, Zhao YL, Chai ZF, Chen CY. Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO2 nanoparticles. Toxicology 2008; 254: 82–90.
- 42 Sheng L, Ze YG, Wang L, Yu XH, Hong J, Zhao XY, Ze X, Liu D, Xu BQ, Zhu YT, Long Y, Lin AA, Zhang C, Zhao Y, Hong FS. Mechanisms of TiO2 nanoparticle-induced neuronal apoptosis in rat primary cultured hippocampal neurons. J Biomed Mater Res Part A 2015; 103A: 1141–1149.
Citing Literature
