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Effects of Tributyltin Chloride on Developing Mouse Oocytes and Preimplantation Embryos

  • Xian-Ju Huang (a1), Ming Shen (a1), Lizhong Wang (a1), Fengxiang Yu (a1), Wangjun Wu (a1) and Hong-lin Liu (a1)...


Tributyltin, an organotin, is ubiquitous in estuaries and freshwater systems. Previous reports suggest that tributyltin is an endocrine disruptor in many wildlife species and it inhibits aromatase in mammalian placental and granulosa-like tumor cell lines. However, no evidence showing the effects of tributyltin on oocytes or preimplantation embryonic developmental competence exists. Therefore, we investigated the role of tributyltin chloride (TBTCl) in the development of female oocytes and preimplantation embryos. Briefly, female ICR mice were gavaged with 0 (vehicle), 4, and 8 mg/kg of TBTCl each day for 18 days. The fluorescence intensity analysis showed that the 5-methylcytosine level decreased after TBTCl treatment, indicating that the general DNA methylation level decreased in the treated oocytes. Our results demonstrate that TBTCl treatment results in decreased mRNA levels of imprinted genes H19, Igf2r, and Peg3 during oocyte growth. The TBTCl-treated oocytes showed a significant increase in reactive oxygen species levels in germinal vesicle oocytes. In TBTCl-treated oocytes, there was no difference in GPx and Sod1 expression, but a decreased mRNA level of Cat occurred when compared with control. Moreover, the blastocysts with TBTCl exposure displayed higher apoptotic signals. These results suggest that TBTCl induces developmental defects in oocytes and preimplantation embryos.


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Agarwal, A., Gupta, S. & Sharma, R. (2005 a). Oxidative stress and its implications in female infertility—A clinician’s perspective. Reprod Biomed Online 11(5), 641650.
Agarwal, A., Gupta, S. & Sharma, R.K. (2005 b). Role of oxidative stress in female reproduction. Reprod Biol Endocrinol 3, 28.
Bourc'his, D., Xu, G.L., Lin, C.S., Bollman, B. & Bestor, T.H. (2001). Dnmt3L and the establishment of maternal genomic imprints. Science 294(5551), 25362539.
Boyer, L.A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L.A., Lee, T.I., Levine, S.S., Wernig, M., Tajonar, A., Ray, M.K., Bell, G.W., Otte, A.P., Vidal, M., Gifford, D.K., Young, R.A. & Jaenisch, R. (2006). Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441(7091), 349353.
Chaube, S.K., Prasad, P.V., Thakur, S.C. & Shrivastav, T.G. (2005). Hydrogen peroxide modulates meiotic cell cycle and induces morphological features characteristic of apoptosis in rat oocytes cultured in vitro. Apoptosis 10(4), 863874.
Ema, M., Kurosaka, R., Amano, H. & Ogawa, Y. (1995). Further evaluation of the developmental toxicity of tributyltin chloride in rats. Toxicology 96(3), 195201.
Ge, Z.J., Luo, S.M., Lin, F., Liang, Q.X., Huang, L., Wei, Y.C., Hou, Y., Han, Z.M., Schatten, H. & Sun, Q.Y. (2014). DNA methylation in oocytes and liver of female mice and their offspring: Effects of high-fat-diet-induced obesity. Environ Health Perspect 122(2), 159164.
Gennari, A., Viviani, B., Galli, C.L., Marinovich, M., Pieters, R. & Corsini, E. (2000). Organotins induce apoptosis by disturbance of [Ca(2+)](i) and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes. Toxicol Appl Pharmacol 169(2), 185190.
Golub, M. & Doherty, J. (2004). Triphenyltin as a potential human endocrine disruptor. J Toxicol Environ Health B Crit Rev 7(4), 281295.
Harazono, A. & Ema, M. (2000). Suppression of decidual cell response induced by tributyltin chloride in pseudopregnant rats: A cause of early embryonic loss. Arch Toxicol 74(10), 632637.
Harazono, A., Ema, M. & Ogawa, Y. (1996). Pre-implantation embryonic loss induced by tributyltin chloride in rats. Toxicol Lett 89(3), 185190.
Harazono, A., Ema, M. & Ogawa, Y. (1998). Evaluation of early embryonic loss induced by tributyltin chloride in rats: Phase- and dose-dependent antifertility effects. Arch Environ Contam Toxicol 34(1), 9499.
Hiura, H., Obata, Y., Komiyama, J., Shirai, M. & Kono, T. (2006). Oocyte growth-dependent progression of maternal imprinting in mice. Genes Cells 11(4), 353361.
Huang, X.J., Wang, X., Ma, X., Sun, S.C., Zhou, X., Zhu, C. & Liu, H. (2013). EZH2 is essential for development of mouse preimplantation embryos. Reprod Fertil Dev 26(8), 11661175.
Inoue, A. & Aoki, F. (2010). Role of the nucleoplasmin 2 C-terminal domain in the formation of nucleolus-like bodies in mouse oocytes. FASEB J 24(2), 485494.
Kondo, Y., Shen, L., Ahmed, S., Boumber, Y., Sekido, Y., Haddad, B.R. & Issa, J.P. (2008). Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. PLoS One 3(4), e2037.
Liu, H., Kim, J.M. & Aoki, F. (2004). Regulation of histone H3 lysine 9 methylation in oocytes and early pre-implantation embryos. Development 131(10), 22692280.
Liu, H.G., Wang, Y., Lian, L. & Xu, L.H. (2006). Tributyltin induces DNA damage as well as oxidative damage in rats. Environ Toxicol 21(2), 166171.
Makita, Y., Omura, M., Tanaka, A. & Kiyohara, C. (2005). Effects of concurrent exposure to tributyltin and 1,1-dichloro-2,2 bis (p-chlorophenyl) ethylene (p,p'-DDE) on immature male Wistar rats. Basic Clin Pharmacol Toxicol 97(6), 364368.
Mamo, S., Gal, A.B., Bodo, S. & Dinnyes, A. (2007). Quantitative evaluation and selection of reference genes in mouse oocytes and embryos cultured in vivo and in vitro. BMC Dev Biol 7, 14.
Morgan, G.T., Jones, P. & Bellini, M. (2012). Association of modified cytosines and the methylated DNA-binding protein MeCP2 with distinctive structural domains of lampbrush chromatin. Chromosome Res 20(8), 925942.
Nakanishi, T. (2008). Endocrine disruption induced by organotin compounds; organotins function as a powerful agonist for nuclear receptors rather than an aromatase inhibitor. J Toxicol Sci 33(3), 269276.
Nakao, M. (2001). Epigenetics: Interaction of DNA methylation and chromatin. Gene 278(1–2), 2531.
Okano, M., Xie, S. & Li, E. (1998). Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19(3), 219220.
Reik, W., Dean, W. & Walter, J. (2001). Epigenetic reprogramming in mammalian development. Science 293(5532), 10891093.
Robertson, K.D. & Wolffe, A.P. (2000). DNA methylation in health and disease. Nat Rev Genet 1(1), 1119.
Sasaki, H. & Matsui, Y. (2008). Epigenetic events in mammalian germ-cell development: Reprogramming and beyond. Nat Rev Genet 9(2), 129140.
Song, Z., Min, L., Pan, Q., Shi, Q. & Shen, W. (2009). Maternal imprinting during mouse oocyte growth in vivo and in vitro. Biochem Biophys Res Commun 387(4), 800805.
Tamaru, H. & Selker, E.U. (2001). A histone H3 methyltransferase controls DNA methylation in Neurospora crassa . Nature 414(6861), 277283.
Tamura, H., Takasaki, A., Miwa, I., Taniguchi, K., Maekawa, R., Asada, H., Taketani, T., Matsuoka, A., Yamagata, Y., Shimamura, K., Morioka, H., Ishikawa, H., Reiter, R.J. & Sugino, N. (2008). Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res 44(3), 280287.
Vielle, A., Lang, J., Dong, Y., Ercan, S., Kotwaliwale, C., Rechtsteiner, A., Appert, A., Chen, Q.B., Dose, A., Egelhofer, T., Kimura, H., Stempor, P., Dernburg, A., Lieb, J.D., Strome, S. & Ahringer, J. (2012). H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation. PLoS Genet 8(9), e1002933.
Wossidlo, M., Nakamura, T., Lepikhov, K., Marques, C.J., Zakhartchenko, V., Boiani, M., Arand, J., Nakano, T., Reik, W. & Walter, J. (2011). 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun 2, 241.
Yan, F., Chen, Y., Zuo, Z., Chen, Y., Yang, Z. & Wang, C. (2009). Effects of tributyltin on epididymal function and sperm maturation in mice. Environ Toxicol Pharmacol 28(1), 1924.
Zucker, R.M., Elstein, K.H., Thomas, D.J. & Rogers, J.M. (1994). Tributyltin and dexamethasone induce apoptosis in rat thymocytes by mutually antagonistic mechanisms. Toxicol Appl Pharmacol 127(1), 163170.



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