Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways

// Jing Liu 1, 2, * , Yong Zhao 1, 3, * , Wei Ge 1 , Pengfei Zhang 1 , Xinqi Liu 1 , Weidong Zhang 1 , Yanan Hao 1 , Shuai Yu 1 , Lan Li 1 , Meiqiang Chu 1 , Lingjiang Min 1 , Hongfu Zhang 3 and Wei Shen 1 1 Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao 266109, P. R. China 2 Core Laboratories of Qingdao Agricultural University, Qingdao 266109, P. R. China 3 State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China * Co-First author Correspondence to: Hongfu Zhang, email: zhanghongfu@caas.cn Wei Shen, email: shenwei427@163.com Keywords: ZnO nanoparticles, oocyte stage exposure, embryo-toxicity, γ-H2AX, NF-κB Received: December 21, 2016 Accepted: April 11, 2017 Published: April 21, 2017 ABSTRACT The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn 2+ . Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.