双酚M通过破坏细胞骨架结构和细胞周期过程抑制小鼠卵母细胞体外成熟

Bisphenol M inhibits mouse oocyte maturation in vitro by disrupting cytoskeleton architecture and cell cycle processes        

双酚M通过破坏细胞骨架结构和细胞周期过程抑制小鼠卵母细胞体外成熟

Authors: Chen H, Liu Y, Huang Y, Zhang P, Du D, Yu W, Wu C, Ruan H, Zhou P, Ding Z, Xiang H.

Source：Reprod Toxicol. 2024 Jul 24;129:108667. doi: 10.1016/j.reprotox.

Abstract

Bisphenol M (BPM), an alternative to bisphenol A (BPA), is commonly utilized in various industrial applications. However, BPM does not represent a safe substitute for BPA due to its detrimental effects on living beings. This research aimed to assess the influence of BPM exposure on the in vitro maturation of mouse oocytes. The findings revealed that BPM exposure had a notable impact on the germinal vesicle breakdown (GVBD) rate and polar body extrusion (PBE) rate throughout the meiotic progression of mouse oocytes, ultimately resulting in meiotic arrest. Investigations demonstrated that oocytes exposure to BPM led to continued activation of spindle assembly checkpoint. Further studies revealed that securin and cyclin B1 could not be degraded in BPM-exposed oocytes, and meiosis could not realize the transition from the MI to the AI stage. Mechanistically, BPM exposure resulted in abnormal spindle assembly and disrupted chromosome alignment of oocytes. Additionally, abnormal positioning of microtubule organizing center-associated proteins implied that MTOC may be dysfunctional. Furthermore, an elevation in the acetylation level of α-tubulin in oocytes was observed after BPM treatment, leading to decreased microtubule stability. In addition to its impact on microtubules, BPM exposure led to a reduction in the expression of the actin, signifying the disruption of actin assembly. Further research indicated a heightened incidence of DNA damage in oocytes following BPM exposure. Besides, BPM exposure induced alterations in histone modifications. The outcomes of this experiment demonstrate that BPM exposure impairs oocyte quality and inhibits meiotic maturation of mouse oocytes.

Keywords: Bisphenol M; Cytoskeleton; Meiosis; Oocyte.

摘要

双酚M（BPM）是双酚A（BPA）的替代品，通常用于各种工业应用。然而，由于BPA对生物的有害影响，BPM并不代表BPA的安全替代品。本研究旨在评估BPM暴露对小鼠卵母细胞体外成熟的影响。结果表明，BPM暴露对小鼠卵母细胞减数分裂过程中的生殖囊泡破裂（GVBD）率和极体排出（PBE）率有显著影响，最终导致减数分裂停滞。研究表明，卵母细胞暴露于BPM导致纺锤体组装检查点的持续激活。进一步研究发现，在BPM处理的卵母细胞中，securin和cyclin B1不能被降解，减数分裂不能实现从MI期到AI期的过渡。机械地，BPM暴露导致异常纺锤体组装和破坏卵母细胞的染色体排列。此外，微管组织中心相关蛋白的异常定位暗示MTOC可能功能失调。此外，在BPM处理后观察到卵母细胞中α-微管蛋白的乙酰化水平升高，导致微管稳定性降低。除了对微管的影响外，BPM暴露还导致肌动蛋白表达的减少，这意味着肌动蛋白组装的破坏。进一步的研究表明，BPM暴露后卵母细胞DNA损伤的发生率增加。此外，BPM暴露诱导组蛋白修饰的改变。本实验的结果表明，BPM暴露损害卵母细胞的质量，并抑制小鼠卵母细胞的减数分裂成熟。

关键词：双酚M;细胞骨架;减数分裂;卵母细胞。