纳米塑料（NPs）最近在全球塑料污染的背景下崭露头角。由于其丰度，微小尺寸和细胞可达性，它们可能比大型塑料垃圾和微塑料碎片更有毒。对于水生动物，纳米塑料的女性生殖毒性已经广泛记录，但对哺乳动物的影响和潜在机制仍不清楚。本研究旨在使用人类卵巢颗粒细胞（GCs）和雌性小鼠探究纳米塑料对女性生殖的影响。通过将荧光聚苯乙烯纳米颗粒（PS-NPs）暴露于人类颗粒肿瘤细胞（KGN细胞）和雌性Balb / c小鼠的卵巢中，评估PS-NPs在这些细胞中和卵巢中的积累。在KGN细胞中分析了增殖和凋亡，活性氧（ROS）和Hippo信号通路相关因子。此外，在雌性小鼠中检查了生育率，产仔数量，卵巢重量和微观结构，卵泡发育，抗米勒尔素激素血清水平以及卵巢凋亡。在这里，PS-NPs可以穿透KGN细胞并积累在卵巢中。体外实验表明，100 μg/ml的PS-NPs抑制了KGN细胞的增殖，诱导了凋亡，积累了ROS，激活了Hippo信号通路的三个关键调节因子（MST1，LATS1和YAP1），并在KGN细胞中下调了CTGF和Cyr61的mRNA水平。此外，提取自红景天的抗氧化化合物沙利度酯可以缓解PS-NPs对KGN的损伤并抑制Hippo信号通路的激活。在体内，每天暴露于1 mg的PS-NPs会导致雌性小鼠生育能力下降，卵巢功能异常，卵巢凋亡增加。总的来说，我们的数据表明，PS-NPs引起颗粒细胞凋亡并影响卵巢功能，从而导致雌性小鼠生育能力降低，这是通过诱导氧化应激和调节Hippo途径发生的。版权所有©2023年该作者。Elsevier Inc.保留所有权利。

Nanoplastics (NPs) have recently emerged in the context of global plastic pollution. They may be more toxic than macroplastics litter and microplastic fragments due to its abundances, tiny sizes, and cellular accessibility. The female reproductive toxicity of NPs has been widely documented for aquatic animals, but their effects and underlying mechanisms remain poorly understood in mammals. This study aimed to explore the effects of NPs on female reproduction using human ovarian granulosa cells (GCs) and female mice. The accumulation of polystyrene NPs (PS-NPs) in human granulosa-like tumor cells (KGN cells) and the ovaries of female Balb/c mice were evaluated by exposure to fluorescent PS-NPs. Proliferation and apoptosis, reactive oxygen species (ROS), and Hippo signaling pathway-related factors were analyzed in KGN cells. In addition, fertility rate, litter size, ovarian weight and microstructure, follicle development, serum level of anti-Mullerian hormone, and apoptosis in ovaries were examined in female mice. Here, the PS-NPs can penetrate the KGN cells and accumulate in the ovaries. In vitro, 100 μg/ml PS-NPs inhibited proliferation, induced apoptosis, accumulated ROS, activated three key regulators of the Hippo signaling pathway (MST1, LATS1, and YAP1), and downregulated the mRNA levels of CTGF and Cyr61 in KGN cells. Furthermore, salidroside, an antioxidative compound extracted from Rhodiola rosea, alleviated the damage of PS-NPs to KGN and inhibited the activation of the Hippo signal pathway. In vivo, exposure to 1 mg/day PS-NPs resulted in decreased fertility, abnormal ovarian function, and increased ovarian apoptosis in female mice. Overall, our data suggest that PS-NPs cause granulosa cell apoptosis and affect ovarian functions, leading to reduced fertility in female mice, by inducing oxidative stress and dysregulating the Hippo pathway.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.