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Int J Biol Sci 2018; 14(13):1834-1844. doi:10.7150/ijbs.27640

Research Paper

Copper Nanoparticles Show Obvious in vitro and in vivo Reproductive Toxicity via ERK Mediated Signaling Pathway in Female Mice

Cai-Hong Zhang1*, Ye Wang2,3*, Qian-Qian Sun1,4*, Lei-Lei Xia1, Jing-Jing Hu5, Kai Cheng5, Xia Wang6, Xin-Xin Fu7, Hang Gu1✉

1. Department of Obstetrics and Gynaecology, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China,
2. Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China,
3. Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China,
4. Department of Gynaecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, People's Republic of China,
5. Clinical Research Center, Changhai Hospital of Second Military Medical University, Shanghai 200433, China,
6. Department of Medical Information, Second Military Medical University, Shanghai, People's Republic of China,
7. Department of Nursing, Second Military Medical University, Shanghai, People's Republic of China.
*Authors contributed equally.

Abstract

Copper nanoparticles (Cu-NPs) and other inorganic nanomaterials have caused increasing concern owing to be widely used. Early studies have reported that they can result in injuries to the kidney, liver and spleen of mice; cause embryonic damage; and inhibit the reproductive capacity of red worms. However, few studies have reported the toxicity of Cu-NPs on the reproductive systems of mammals. In the present work, we explored the cytotoxicity of Cu-NPs in human extravillous trophoblast cells and in the reproductive organs of mice. Cu-NPs induced ovarian and placental pathophysiology and dysfunction in mice. These nanoparticles also induced apoptosis and suppressed the proliferation of human extravillous trophoblast cells and caused cell cycle arrest at the G2/M phase in a time-and dose-dependent manner. Cu-NPs can significantly damage the mitochondrial membrane potential (MMP), which suggests that Cu-NPs can activate the mitochondria-mediated apoptosis signaling pathway. We also observed that Cu-NPs significantly inhibit the expression of BRAF, ERK, and MITF expression, all of which are important genes in the ERK signaling pathway. Our research demonstrated that Cu-NPs exert obvious reproductive toxicity in mice by disrupting the balance of sex hormones and exert cytotoxicity on human extravillous trophoblast cells, and ERK signaling and the mitochondrial apoptosis pathway made great contribution to the toxicity of Cu-NPs on female mice.

Keywords: Cu-NPs, human extravillous trophoblast cell, ERK mitochondria membrane potential, reproductive toxicity

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How to cite this article:
Zhang CH, Wang Y, Sun QQ, Xia LL, Hu JJ, Cheng K, Wang X, Fu XX, Gu H. Copper Nanoparticles Show Obvious in vitro and in vivo Reproductive Toxicity via ERK Mediated Signaling Pathway in Female Mice. Int J Biol Sci 2018; 14(13):1834-1844. doi:10.7150/ijbs.27640. Available from http://www.ijbs.com/v14p1834.htm