In-utero exposure to HT-2 toxin affects meiotic progression and early oogenesis in foetal oocytes by increasing oxidative stress

Hong, Yi; Mu, Xinyi; Ji, Xingduo; Chen, Xuemei; Geng, Yanqing; Zhang, Yan; Liu, Qiqi; Li, Fangfang; Wang, Yingxiong; He, Junlin

In-utero exposure to HT-2 toxin affects meiotic progression and early oogenesis in foetal oocytes by increasing oxidative stress

2021

HT-2 toxin (HT-2), a mycotoxin produced by Fusarium species, is detected in a variety of cereal grain-based human food and animal feed. Apart from its well-established immunotoxicity and haematotoxicity, it also causes reproductive disorders. In the present study, we revealed the adverse effects of HT-2 on early oogenesis at the foetal stage. Pregnant mice were orally administered with HT-2 for 3 days at mid-gestation. Oocytes from female foetuses exposed to HT-2 displayed defects in meiotic prophase, including unrepaired DNA damage, elevated recombination levels, and reduced expression of meiotic-related genes. Subsequently, increased oxidative stress was observed in the foetal ovaries exposed to HT-2, along with the elevated levels of reactive oxygen species, malondialdehyde, catalase, and superoxide dismutase 1/2, thereby resulting in impaired mitochondrial membrane potential and cell apoptosis. Furthermore, pre-treatment with urolithin A, a natural compound with antioxidant activities, partially reversed the delayed meiotic process by alleviating oxidative stress. Since early oogenesis is essential to determine female fertility in adult life, this study indicated that brief maternal exposure to HT-2 toxin may compromise the fertility of a developing female foetus.

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