Ding Zhiming, Chen Huilei, Cheng Huiru, Wu Caiyun, Ruan Hongzhen, Zhu Bingjing, Zhou Ping, Xu Zuying, Xiang Huifen
NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei 230032, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, China.
NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei 230032, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Bengbu Medical University, No.287 Changhuai Road, Bengbu 233000, China.
Ecotoxicol Environ Saf. 2025 Jan 1;289:117693. doi: 10.1016/j.ecoenv.2025.117693. Epub 2025 Jan 8.
The use of Bisphenol A (BPA) has been widely restricted due to its adverse health effects. Bisphenol Z (BPZ) is used as an alternative to BPA, and humans are widely exposed to BPZ through various routes. Recent studies have shown that BPZ exposure adversely affects mouse oocyte meiotic maturation. This study investigates the impact of BPZ exposure on early mouse embryonic development alongside an exploration of the underlying mechanisms. The findings reveal that exposure to BPZ leads to a reduction in early embryo quality and hinders developmental progression. RNA sequencing analysis has identified 593 differentially expressed genes as a result of BPZ exposure, highlighting considerable changes in early embryonic gene expression. Mechanistically, BPZ exposure inhibits the activation of the zygotic genome and impedes maternal mRNA degradation, thereby interfering with maternal-to-zygotic transition (MZT). Further analysis indicates compromised mitochondrial function, as evidenced by abnormal distribution, diminished membrane potential, and lower ATP levels. Consequently, BPZ-exposed embryos exhibit elevated levels of reactive oxygen species, superoxide anions, and oxidative DNA damage. Moreover, BPZ exposure is associated with an increase in γ-H2A.X expression. Additionally, BPZ exposure alters the expression levels of histone modifications, including H3K27me2, H3K27me3, H3K9me3, and H3K27ac, in early embryos. Collectively, BPZ exposure significantly impairs early embryo quality by disrupting mitochondrial function, inducing oxidative stress and DNA damage, altering histone modifications, and inhibiting MZT, ultimately resulting in hindered blastocyst formation. These findings underscore the profound adverse effects of BPZ on early embryonic development, indicating the need for caution when considering it as a safe alternative to BPA.
由于双酚A（BPA）对健康有不利影响，其使用已受到广泛限制。双酚Z（BPZ）被用作BPA的替代品，人类通过各种途径广泛接触BPZ。最近的研究表明，接触BPZ会对小鼠卵母细胞减数分裂成熟产生不利影响。本研究调查了BPZ暴露对小鼠早期胚胎发育的影响，并探索其潜在机制。研究结果表明，接触BPZ会导致早期胚胎质量下降并阻碍发育进程。RNA测序分析确定了593个因BPZ暴露而差异表达的基因，突出了早期胚胎基因表达的显著变化。从机制上讲，BPZ暴露会抑制合子基因组的激活并阻碍母体mRNA的降解，从而干扰母源-合子转换（MZT）。进一步分析表明线粒体功能受损，表现为分布异常、膜电位降低和ATP水平下降。因此，接触BPZ的胚胎表现出活性氧、超氧阴离子水平升高以及氧化性DNA损伤。此外，BPZ暴露与γ-H2A.X表达增加有关。另外，BPZ暴露会改变早期胚胎中组蛋白修饰的表达水平，包括H3K27me2、H3K27me3、H3K9me3和H3K27ac。总体而言，BPZ暴露通过破坏线粒体功能、诱导氧化应激和DNA损伤、改变组蛋白修饰以及抑制MZT，显著损害早期胚胎质量，最终导致囊胚形成受阻。这些发现强调了BPZ对早期胚胎发育的深远不利影响，表明在将其视为BPA的安全替代品时需要谨慎。
