Reproductive Medicine Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China; Shandong Provincial Key Medical and Health Laboratory of Reproductive Health and Genetics (Yantai Yuhuangding Hospital), China.
Reproductive Medicine Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China; Shandong Provincial Key Medical and Health Laboratory of Reproductive Health and Genetics (Yantai Yuhuangding Hospital), China.
Ecotoxicol Environ Saf. 2024 Sep 15;283:116798. doi: 10.1016/j.ecoenv.2024.116798. Epub 2024 Jul 30.
Propylparaben (PrPB) is a known endocrine disrupting chemicals that is widely applied as preservative in pharmaceuticals, food and cosmetics. PrPB has been detected in human urine samples and human serum and has been proven to cause functional decline in reproduction. However, the direct effects of PrPB on mammalian oocyte are still unknown. Here, we demonstrationed that exposure to PrPB disturbed mouse oocyte maturation in vitro, causing meiotic resumption arrest and first polar body extrusion failure. Our results indicated that 600 μM PrPB reduced the rate of oocyte germinal vesicle breakdown (GVBD). Further research revealed that PrPB caused mitochondrial dysfunction and oxidative stress, which led to oocyte DNA damage. This damage further disturbed the activity of the maturation promoting factor (MPF) complex Cyclin B1/ Cyclin-dependent kinase 1 (CDK1) and induced G2/M arrest. Subsequent experiments revealed that PrPB exposure can lead to spindle morphology disorder and chromosome misalignment due to unstable microtubules. In addition, PrPB adversely affected the attachment between microtubules and kinetochore, resulting in persistent activation of BUB3 amd BubR1, which are two spindle-assembly checkpoint (SAC) protein. Taken together, our studies indicated that PrPB damaged mouse oocyte maturation via disrupting MPF related G2/M transition and SAC depended metaphase-anaphase transition.
对羟基苯甲酸丙酯（PrPB）是一种已知的内分泌干扰化学物质，广泛应用于药物、食品和化妆品中作为防腐剂。PrPB 已在人类尿液样本和血清中被检测到，并已被证明会导致生殖功能下降。然而，PrPB 对哺乳动物卵母细胞的直接影响尚不清楚。在这里，我们证明了暴露于 PrPB 会干扰体外培养的小鼠卵母细胞成熟，导致减数分裂恢复阻滞和第一极体排出失败。我们的结果表明，600μM 的 PrPB 降低了卵母细胞生发泡破裂（GVBD）的速率。进一步的研究表明，PrPB 导致线粒体功能障碍和氧化应激，从而导致卵母细胞 DNA 损伤。这种损伤进一步扰乱了成熟促进因子（MPF）复合物细胞周期蛋白 B1/细胞周期蛋白依赖性激酶 1（CDK1）的活性，并诱导 G2/M 期阻滞。随后的实验表明，PrPB 暴露会由于微管不稳定导致纺锤体形态紊乱和染色体排列不齐。此外，PrPB 还会对微管和动粒之间的附着产生不利影响，导致纺锤体装配检查点（SAC）蛋白 BUB3 和 BubR1 的持续激活。总之，我们的研究表明，PrPB 通过破坏与 MPF 相关的 G2/M 转换和 SAC 依赖的中期-后期转换来破坏小鼠卵母细胞成熟。
