Iodoacetic acid disrupts mouse oocyte maturation by inducing oxidative stress and spindle abnormalities

Abstract

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 dosedependent 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 γ -H2AX focus number. In addition, the unarrested oocytes entered metaphase II (MII) with severe defects in spindle morphologies and chromosome alignment after 14-hour 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 IAAinduced 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.

Melatonin Protects Against Mdivi-1-Induced Abnormal Spindle Assembly and Mitochondrial Superoxide Production During Porcine Oocyte Maturation

“…In previous studies, Rad51 deficiency or knockout caused abnormal spindle assembly in mammalian oocytes ( Kim et al, 2016 ). γ-H2ax was well known to DNA damaged gene in oocytes, which has also been used as evidence of abnormal spindle assembly by double-strand breaks (DSBs) in mouse oocyte maturation ( Jia et al, 2019 ; Jiao et al, 2020 ). We investigated Rad51 and γ-H2ax expression levels to confirm the extent of DNA damage by Mdivi-1 treatment.…”

Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women

“…In addition, in vivo experiments in rats, mice, and pigs have also demonstrated the reproductive toxicity of DBPs. Research indicates that exposure to DBPs interferes with the maturation of mouse oocytes by increasing ROS levels, disrupting spindle assembly, inducing DNA damage, and causing meiotic arrest ( Jiao et al, 2021 ).…”

Chloroacetonitrile reduces rat prenatal bone length and induces oxidative stress, apoptosis, and DNA damage in rat fetal liver

“…DBPs have been shown to have negative effects on female reproductive function, including delayed puberty (Parvez et al, 2017), increased estrogen production (Goldman, Murr, Buckalew, Ferrell, & Cooper, 2007), impaired ovarian steroidogenesis (Jeong et al, 2016; Jiao, Gonsioroski, Flaws, & Qiao, 2021). In mouse ovarian follicles, monohalogenated DBPs (chloroacetic acid [CAA]; bromoacetic acid [BAA]; iodoacetic acid [IAA]) suppress steroidogenesis and antral follicle growth (Jeong et al, 2016).…”