期刊
ENVIRONMENTAL POLLUTION
卷 268, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.envpol.2020.115601
关键词
Iodoacetic acid; Mouse oocyte; Oxidative stress; Spindle assembly; DNA damage
资金
- National Institutions of Health (NIH) in the United States [NIH ROO HD082375, NIH ROl GM135549, NIH R21 E5028963]
- NIH [ROl GM135549, R21 E5028963]
Exposure to iodoacetic acid (IAA) has adverse effects on mouse oocyte maturation, including metaphase I arrest, polar-body-extrusion failure, abnormal spindle assembly, and chromosome misalignment. IAA exposure increases ROS levels, induces DNA damage, and mediates maturation failure in oocytes through oxidative stress.
Disinfection by-products (DBPs) are compounds produced during the water disinfection process. Iodoacetic acid (IAA) is one of the unregulated DBPs in drinking water, with potent cytotoxicity and genotoxicity in animals. However, whether IAA has toxic effects on oocyte maturation remains unclear. Here, we show that IAA exposure resulted in metaphase I (MI) arrest and polar-body-extrusion failure in mouse oocytes, indicating that IAA had adverse effects on mouse oocyte maturation in vitro. Particularly, IAA treatment caused abnormal spindle assembly and chromosome misalignment. Previous studies reported that IAA is a known inducer of oxidative stress in non-germline cells. Correspondingly, we found that IAA exposure increased the reactive oxygen species (ROS) levels in oocytes in a dose-dependent manner, indicating IAA exposure could induce oxidative stress in oocytes. Simultaneously, DNA damage was also elevated in the nuclei of these IAA-exposed mouse oocytes, evidenced by increased gamma-H2AX focus number. In addition, the un-arrested oocytes entered metaphase II (MII) with severe defects in spindle morphologies and chromosome alignment after 14-h IAA treatment. An antioxidant, N-acetyl-L-cysteine (NAC), reduced the elevated ROS level and restored the meiotic maturation in the IAA-exposed oocytes, which indicates that IAA-induced maturation failure in oocytes was mainly mediated by oxidative stress. Collectively, our results indicate that IAA exposure interfered with mouse oocyte maturation by elevating ROS levels, disrupting spindle assembly, inducing DNA damage, and causing MI arrest. Published by Elsevier Ltd.
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