With rapid increase in the global use of various plastics, microplastics (MPs) and nanoplastics (NPs) pollution and their adverse health effects have attracted global attention. MPs have been detected out in human body and both MPs and NPs showed female reproductive toxicological effects in animal models. Miscarriage (abnormal early embryo loss), accounting for 15-25% pregnant women worldwide, greatly harms human reproduction. However, the adverse effects of NPs on miscarriage have never been explored. In this study, we identified that polystyrene (PS) plastics particles were present in women villous tissues. Their levels were higher in villous tissues of unexplained recurrent miscarriage (RM) patients vs. healthy control (HC) group. Furthermore, mouse assays further confirmed that exposure to polystyrene nanoplastics (PS-NPs, 50 nm in diameter, 50 or 100 mg/kg) indeed induced miscarriage. In mechanism, PS-NPs exposure (50, 100, 150, or 200 µg/mL) increased oxidative stress, decreased mitochondrial membrane potential, and increased apoptosis in human trophoblast cells by activating Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3 signaling through mitochondrial pathway. The alteration in this signaling was consistent in placental tissues of PS-NPs-exposed mouse model and in villous tissues of unexplained RM patients. Supplement with Bcl-2 could efficiently suppress apoptosis in PS-NPs-exposed trophoblast cells and reduce apoptosis and alleviate miscarriage in PS-NPs-exposed pregnant mouse model. Exposure to PS-NPs activated Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3, leading to excessive apoptosis in human trophoblast cells and in mice placental tissues, further inducing miscarriage.

中文翻译：

---

接触高剂量聚苯乙烯纳米塑料会导致滋养层细胞凋亡并诱发流产

随着全球各种塑料使用量的迅速增加，微塑料（MP）和纳米塑料（NP）污染及其对健康的不良影响引起了全球的关注。MPs已在人体内检出，MPs和NPs在动物模型中均表现出对女性生殖的毒理作用。流产（异常的早期胚胎丢失）占全世界孕妇的15-25%，极大地危害了人类的生殖。然而，纳米粒子对流产的不利影响从未被探索过。在这项研究中，我们发现女性绒毛组织中存在聚苯乙烯 (PS) 塑料颗粒。与健康对照组 (HC) 组相比，不明原因反复流产 (RM) 患者的绒毛组织中的水平较高。此外，小鼠实验进一步证实，接触聚苯乙烯纳米塑料（PS-NP，直径50纳米，50或100毫克/千克）确实会引起流产。在机制上，PS-NPs暴露（50、100、150或200 µg/mL）通过激活Bcl-2/Cleaved-caspase-2/Cleaved-增加氧化应激，降低线粒体膜电位，并增加人滋养层细胞的凋亡。 Caspase-3 信号传导通过线粒体途径。这种信号的改变在暴露于 PS-NPs 的小鼠模型的胎盘组织和不明原因 RM 患者的绒毛组织中是一致的。补充Bcl-2可以有效抑制PS-NPs暴露的滋养层细胞的凋亡，并在PS-NPs暴露的妊娠小鼠模型中减少细胞凋亡并减轻流产。暴露于PS-NPs会激活Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3，导致人滋养层细胞和小鼠胎盘组织过度凋亡，进一步诱发流产。