Bisphenol Z exposure inhibits oocyte meiotic maturation by rupturing mitochondrial function.

The use of bisphenol A (BPA) has been restricted due to its endocrine-disrupting effects. As a widely used alternative to BPA today, environmental levels of bisphenol Z (BPZ) continue to rise and accumulate in humans. Oocyte quality is critical for a successful pregnancy. Nevertheless, the toxic impacts of BPZ on the maturation of mammalian oocytes remain unexplored. Therefore, the impacts of BPZ and BPA on oocyte meiotic maturation were compared in an in vitro mouse oocyte culture model. Exposure to 150 µM of both BPZ and BPA disrupted the assembly of the meiotic spindle and the alignment of chromosomes, and BPZ exerted stronger toxicological effects than BPA. Furthermore, BPZ resulted in aberrant expression of F-actin, preventing the formation of the actin cap. Mechanistically, BPZ exposure disrupted the mitochondrial localization pattern, reduced mitochondrial membrane potential and ATP content, leading to impaired mitochondrial function. Further studies revealed that BPZ exposure resulted in oxidative stress and altered expression of genes associated with anti-oxidative stress. Moreover, BPZ induced severe DNA damage and triggered early apoptosis in oocytes, accompanied by impaired lysosomal function. Overall, the data in this study suggest that BPZ is not a safe alternative to BPA. BPZ can trigger early apoptosis by affecting mitochondrial function and causing oxidative stress and DNA damage in oocytes. These processes disrupt cytoskeletal assembly, arrest the cell cycle, and ultimately inhibit oocyte meiotic maturation.

Aberrant expression of UBE2C in endometrial cancer and its correlation to epithelial mesenchymal transition.

Ubiquitin-conjugating enzyme E2C (UBE2C), its overexpression promotes tumor progression, is a key component of the ubiquitin conjugating proteasome complex. Epithelial-mesenchymal transition, which is lost epithelial features and gained mesenchymal features in some epithelial cancers, is involved in epithelial cancers' invasiveness and metastasis. The aim of this study is to detect the expression of UBE2C, WNT5α, and E-cad in endometrial cancer (EC) and their clinical significance. The expression of UBE2C, WNT5α, and ZEB1 in 125 cases EC tissues were detected by immunohistochemistry. Patients clinicopathological, demography, and follow-up data were also collected. Positive rates of expression of UBE2C and ZEB1 were significantly higher in EC tissues when compared with the control tissues. The positive expression of UBE2C and ZEB1 were positively associated with tumor stages, local lymph node metastasis, and International Federation of Gynecology and Obstetrics (FIGO) stages. The positive rate of expression of WNT5a was significantly lower in EC tissues when compared with the control tissues. And positive expression of E-cad was inversely related to tumor stages, lymph node metastasis stages, and FIGO stages. Kaplan-Meier analyses demonstrated that positive expression of UBE2C or ZEB1 for EC patients had unfavorably overall survival time when compared with patients with negative expression of UBE2C or ZEB1. And EC patients with positive expression of WNT5a had favorably overall survival time when compared with EC patients with negative expression of WNT5a. Multivariate analysis demonstrated that positive expression UBE2C, WNT5α, and ZEB1, as well as FIGO stages were independent prognostic factors for EC patients. UBE2C, ZEB1, and WNT5a should be considered promising biomarkers for EC patients' prognosis.