Methylmercury Chloride Inhibits Meiotic Maturation of Mouse Oocytes in Vitro by Disrupting the Cytoskeleton.

Methylmercury chloride (MMC) is a persistent heavy metal contaminant that can bioaccumulate in humans via the food chain, exerting detrimental effects on health. Nevertheless, the specific influence of MMC on oocyte meiotic maturation has yet to be elucidated. This research demonstrated that MMC exposure during the in vitro cultivation of mouse oocytes did not influence germinal vesicle breakdown but markedly decreased oocyte maturation rates. Subsequent analysis indicated that MMC exposure resulted in aberrant spindle morphology and disorganized chromosome alignment, alongside continuous activation of the spindle assembly checkpoint (SAC). However, MMC exposure didn't alter the localization pattern of microtubule-organizing center-associated proteins. MMC exposure considerably diminished the acetylation level of α-tubulin, signifying reduced microtubule stability. Additionally, MMC exposure disrupted the dynamic alterations of F-actin. MMC exposure didn't affect mitochondrial localization, mitochondrial membrane potential, adenosine triphosphate content or the concentrations of reactive oxygen species. Nonetheless, MMC exposure triggered DNA damage and modified histone modification levels. Consequently, the defects in oocyte maturation induced by MMC exposure can be attributed to impaired cytoskeleton dynamics and DNA damage. This study offers the first comprehensive elucidation of the negative impacts of MMC on oocyte maturation, highlighting the potential reproductive health risks associated with MMC exposure.

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

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.

Sirtuin 5-driven meiotic spindle assembly and actin-based migration in mouse oocyte meiosis.

Sirtuin 5 (Sirt5), a member of the Sirtuin family, is involved in various intracellular biological processes. However, the function of Sirt5 in oocyte maturation has not been clearly elucidated. In this study, we observed that Sirt5 was persistently expressed during the meiotic division of mouse oocytes, with a notable decline in expression in aging oocytes. Sirt5 inhibition led to the failure of the first polar body extrusion and induced cell cycle arrest, indicative of unsuccessful oocyte maturation. Furthermore, Sirt5 inhibition was associated with the extrusion of abnormally large polar bodies, suggesting disrupted asymmetric oocyte division. Mechanistically, the inhibition of Sirt5 resulted in aberrant spindle assembly and disordered chromosome alignment in oocytes. Moreover, Sirt5 inhibition caused the spindle to be centrally located in the oocyte without migrating to the cortical region, consequently preventing the formation of the actin cap. Further investigation revealed that Sirt5 inhibition notably diminished the expression of phosphorylated cofilin and profilin1, while increasing cytoplasmic F-actin levels. These findings suggest that Sirt5 inhibition during oocyte maturation adversely affects spindle assembly and chromosome alignment and disrupts actin dynamics impairing spindle migration and contributing to the failure of symmetric oocyte division and maturation.

Triphenyltin chloride exposure inhibits meiotic maturation of mouse oocytes by disrupting cytoskeleton assembly and cell cycle progression.

Triphenyltin chloride (TPTCL) is widely used in various industrial and agricultural applications. This study aimed to elucidate the mechanisms underlying the toxicological effects of TPTCL on oocytes. The obtained findings revealed that TPTCL exposure reduced polar body extrusion (PBE) and induced meiotic arrest. Mechanistically, TPTCL disrupted meiotic spindle assembly and chromosome alignment. Further analysis indicated a significant decrease in p-MAPK expression, and disturbances in the localization of Pericentrin and p-Aurora A in TPTCL exposed oocytes, which suggesting impaired microtubule organizing center (MTOC)function. Moreover, TPTCL exposure enhance microtubule acetylation and microtubule instability. Therefore, the spindle assembly checkpoint (SAC) remained activated, and the activity of the anaphase-promoting complex (APC) was inhibited, thereby preventing oocytes from progressing into the entering anaphase I (AI) stage. TPTCL exposure also augmented the actin filaments in the cytoplasm. Notably, mitochondrial function appeared unaffected by TPTCL, as evidenced indicated by stable mitochondrial membrane potential and ATP content. Furthermore, TPTCL treatment altered H3K27me2, H3K27me3 and H3K9me3 levels, suggesting changes in epigenetic modifications in oocytes. Taken together, our results suggest that TPTCL disrupts cytoskeleton assembly, continuously activates SAC, inhibits APC activity, and blocks meiotic progression, ultimately impair oocyte maturation.

Carbendazim exposure inhibits mouse oocytes meiotic maturation in vitro by destroying spindle assembly.

Successful fertilization and early embryonic development heavily depend on the quality of the oocytes. Carbendazim (CBZ), a broad-spectrum fungicide, is widely available in the environment and has adverse effects on organisms. The present study focused on exploring the potential reproductive toxicity of CBZ exposure by investigating its effects on the maturation of mouse oocytes. The results demonstrated that although no disruptions were observed in the G2/M stage transition for meiosis resumption, CBZ did hinder the polar body extrusion (PBE) occurring during oocyte maturation. Cell cycle distribution analysis revealed that CBZ exposure interfered with the meiotic process, causing oocytes to be arrested at the metaphase I (MI) stage. The subsequent investigation highlighted that CBZ exposure impeded the spindle assembly and chromosomal alignment, which was linked to a decline in the level of p-MAPK. Additionally, CBZ exposure adversely affected the kinetochore-microtubule (K-MT) attachment, leading to the persistent activation of the spindle-assembly checkpoint (SAC). The study further noticed a substantial rise in the acetylation of α-tubulin and a reduction in spindle microtubule stability in CBZ-treated oocytes. In addition, the distribution pattern of estrogen receptor alpha (ERα) was altered in oocytes treated with CBZ, with abnormal aggregation on the spindles. CBZ exposure also resulted in altered histone modifications. A notable finding from this research was that the meiotic maturation of some oocytes remained unaffected even after CBZ treatment. However, during the ensuing metaphase II (MII) stage, these oocytes displayed anomalies in their spindle morphology and chromosome arrangement and diminished ability to bind to the sperm. The observations made in this study underscore the potential for CBZ to disrupt the meiotic maturation of oocytes, leading to a decline in the overall quality of oocytes.