Abstract
Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals.
Highlights
Diquat (1,10-ethylene-2,20-bipyridilium) is a bipyridyl herbicide for the control of aquatic weeds and broad-leaved weeds among fruit, vegetables, and as a preharvest desiccant for seed and fodder crops such as rice and sunflower[1]
We examined the toxic effects of diquat on oocyte development competence, reactive oxygen species (ROS) levels in granulosa cells and oocytes, granulosa cell apoptosis, early embryo development in vivo, and litter sizes
We found that chronic exposure to diquat had adverse effects on oocyte quality, follicular development, fetus development and litter sizes
Summary
Diquat (1,10-ethylene-2,20-bipyridilium) is a bipyridyl herbicide for the control of aquatic weeds and broad-leaved weeds among fruit, vegetables, and as a preharvest desiccant for seed and fodder crops such as rice and sunflower[1]. Superoxide anion radical generation and subsequently hydrogen peroxide production are thought to be key cytotoxic mechanisms induced by diquat [2]. High dose injection with diquat causes liver necrosis, lung injury, and animal death due to acute oxidative stress generation [3,4,5]. It is reported that diquat exposure caused 10–40 times higher ROS production compared to paraquat [6]. Weaned pigs treated with diquat can cause obvious reduction in activities of antioxidant enzymes and enhancement in malondialdehyde (MDA) concentration in the plasma and liver.
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