背景:Sterigmatocystin(STE)是一种广泛存在于受污染的食品和食品中的霉菌毒素,过度长期接触STE与一些健康问题有关,包括不孕症。然而,关于STE毒素对女性生殖系统的影响的信息很少,特别是关于卵母细胞成熟。
方法:在本研究中,我们研究了STE对小鼠卵母细胞成熟的毒性作用。我们还使用了蛋白质印迹,免疫荧光,和图像定量分析,以评估STE暴露对卵母细胞成熟进程的影响,线粒体分布,氧化应激,DNA损伤,卵母细胞铁性和不对称分裂缺陷。
结果:我们的结果表明,STE暴露破坏了小鼠卵母细胞的成熟进程。当我们检查100µMSTE治疗后的细胞变化时,我们发现STE对极体挤压产生不利影响,并诱导卵母细胞不对称分裂缺陷。RNA测序数据显示,STE暴露影响小鼠卵母细胞减数分裂过程中几种通路相关基因的表达,表明其对卵母细胞的毒性。基于RNA-seq数据,我们发现STE暴露会引起卵母细胞的氧化应激并引起DNA损伤。此外,在暴露于STE的卵母细胞中也发现了铁凋亡和α-微管蛋白乙酰化。此外,我们确定STE暴露导致小鼠卵母细胞RAF1蛋白表达减少,RAF1活性的抑制也会导致小鼠卵母细胞不对称分裂的缺陷。
结论:总的来说,我们的研究为STE导致减数分裂异常的分子机制提供了新的见解。
BACKGROUND: Sterigmatocystin (STE) is a mycotoxin widely found in contaminated food and foodstuffs, and excessive long-term exposure to STE is associated with several health issues, including infertility. However, there is little information available regarding the effects of STE toxin on the female reproductive system, particularly concerning oocyte maturation.
METHODS: In the present study, we investigated the toxic effects of STE on mouse oocyte maturation. We also used Western blot, immunofluorescence, and image quantification analyses to assess the impact of STE exposure on the oocyte maturation progression, mitochondrial distribution, oxidative stress, DNA damages, oocyte ferroptosis and asymmetric division defects.
RESULTS: Our results revealed that STE exposure disrupted mouse oocyte maturation progression. When we examined the cellular changes following 100 µM STE treatment, we found that STE adversely affected polar body extrusion and induced asymmetric division defects in oocytes. RNA-sequencing data showed that STE exposure affects the expression of several pathway-correlated genes during oocyte
meiosis in mice, suggesting its toxicity to oocytes. Based on the RNA-seq data, we showed that STE exposure induced oxidative stress and caused DNA damage in oocytes. Besides, ferroptosis and α-tubulin acetylation were also found in STE-exposed oocytes. Moreover, we determined that STE exposure resulted in reduced RAF1 protein expression in mouse oocytes, and inhibition of RAF1 activity also causes defects in asymmetric division of mouse oocytes.
CONCLUSIONS: Collectively, our research provides novel insights into the molecular mechanisms whereby STE contributes to abnormal
meiosis.