Diisononyl phthalate (DINP), a mixture of chemical compounds composed of diverse isononyl esters of phthalic acid, is commonly applied as a plasticizer to substitute for di (2-ethylhexyl) phthalate (DEHP). It has been demonstrated that DINP exposure impairs the functions of kidney and liver in animals. However, the effects and potential mechanisms of DINP exposure on the female reproduction, especially the oocyte quality are still poorly understood. Here, we discovered that DINP exposure weakened the porcine oocyte meiotic competency (78.9% vs 53.6%, P < 0.001) and fertilization ability (78.5% vs 34.1%, P < 0.0001) during in vitro maturation. Specifically, DINP exposure induced the persistent spindle assembly checkpoint (SAC) activation caused by the disorganized spindle/chromosome apparatus (spindle: 20.0% vs 83.3%, P < 0.001; chromosome: 20.0% vs 80.0%, P < 0.01) to arrest meiotic progression of oocytes at metaphase I stage. In addition, DINP exposure disturbed the dynamics of sperm binding (146.7 vs 58.6, P < 0.0001) and fusion proteins (19.5 vs 11.6, P < 0.0001) in oocytes to compromise their fertilization ability. In particular, transcriptome data uncovered that the action mechanism of DINP on the oocyte maturation was associated with oxidative phosphorylation, apoptosis and autophagy pathways. Lastly, we validated that DINP exposure resulted in the mitochondrial dysfunction (27.2 vs 19.8, P < 0.0001) and elevated levels of reactive oxygen species (ROS; 8.9 vs 19.9, P < 0.0001) to trigger the occurrence of apoptosis (7.2 vs 13.1, P < 0.0001) and protective autophagy (68.6 vs 139.3, P < 0.01). Altogether, our findings not only testify that DINP has a potentially adverse impact on the mammalian oocyte quality, but also provide a scientific reference regarding how environment pollutants act on the female germ cell development.

中文翻译：

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暴露于邻苯二甲酸二异壬酯会诱导细胞凋亡，从而降低猪卵母细胞的质量。

邻苯二甲酸二异壬酯 (DINP) 是由多种邻苯二甲酸异壬酯组成的化合物混合物，通常用作增塑剂来替代邻苯二甲酸二（2-乙基己基）酯 (DEHP)。已经证明，接触 DINP 会损害动物的肾脏和肝脏功能。然而，DINP 暴露对雌性生殖，尤其是卵母细胞质量的影响和潜在机制仍知之甚少。在这里，我们发现在体外成熟过程中，DINP 暴露削弱了猪卵母细胞减数分裂能力（78.9% 对 53.6%，P < 0.001）和受精能力（78.5% 对 34.1%，P < 0.0001）。具体而言，DINP 暴露诱导了由杂乱无章的纺锤体/染色体装置引起的持续纺锤体组装检查点 (SAC) 激活（纺锤体：20.0% 对 83.3%，P < 0.001；染色体：20.0% 对 80.0%，P < 0.01) 阻止中期 I 期卵母细胞的减数分裂进程。此外，DINP 暴露扰乱了卵母细胞中精子结合（146.7 对 58.6，P < 0.0001）和融合蛋白（19.5 对 11.6，P < 0.0001）的动力学，从而损害了它们的受精能力。特别是，转录组数据揭示了 DINP 对卵母细胞成熟的作用机制与氧化磷酸化、细胞凋亡和自噬途径有关。最后，我们验证了 DINP 暴露导致线粒体功能障碍（27.2 vs 19.8，P < 0.0001）和活性氧水平升高（ROS；8.9 vs 19.9，P < 0.0001）以触发细胞凋亡的发生（7.2 vs 13.1， P < 0.0001）和保护性自噬（68.6 对 139.3，P < 0.01）。共，