Abstract：
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.
摘要：
对羟基苯甲酸丙酯（PrPB）是一种已知的内分泌干扰化学物质，被广泛用作药物中的防腐剂，食品和化妆品。已在人尿液样品和人血清中检测到PrPB，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作用尚不清楚。这里,我们证明暴露于PrPB会干扰体外小鼠卵母细胞的成熟，导致减数分裂恢复停滞和第一极体挤压失败。我们的结果表明，600μMPrPB可降低卵母细胞胚泡破裂（GVBD）的速率。进一步的研究表明，PrPB引起线粒体功能障碍和氧化应激，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CyclinB1/Cyclin依赖性激酶1（CDK1）的活性，并诱导了G2/M阻滞。随后的实验表明，由于微管不稳定，PrPB暴露会导致纺锤体形态紊乱和染色体错位。此外,PrPB对微管和动核之间的附着产生不利影响，导致BUB3和BubR1持续激活，这是两个纺锤体组装检查点（SAC）蛋白。一起来看,我们的研究表明，PrPB通过破坏MPF相关的G2/M过渡和SAC依赖的中期-后期过渡来破坏小鼠卵母细胞的成熟。
