Wu Hua, Feng Lihua, Wu Huang, Wang Lihong, Xu Hengyi, Fu Fen
The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China; State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China.
The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China.
Ecotoxicol Environ Saf. 2025 Jan 15;290:117622. doi: 10.1016/j.ecoenv.2024.117622. Epub 2024 Dec 27.
Nanoplastics (NPs) are an emerging class of pollutants. They can act as a"Trojan horse" to change the bioavailability and toxicity of heavy metals in the environment. However, research on the combined toxicity of heavy metals and NPs is scarce, especially during the critical developmental period of adolescence. In this study, polystyrene nanoplastics (PS-NPs) and/or cadmium (Cd) were exposed to 4-week-old female rats for 28 days, with the aim of exploring the potential effects of combined exposure to PS-NPs and Cd on the ovaries of adolescence rats. Results showed that co-exposure to PS-NPs and Cd exacerbated ovarian toxicity in rats, primarily through increased atretic follicle numbers and endocrine disruption. Further studies revealed that PS-NPs and Cd synergistically repressed the SIRT3-SOD2/Gpx4 pathway, inducing mitochondrial oxidative stress and ferroptosis, resulting in damage to ovarian structure and function. However, the addition of the mitochondrion-targeted antioxidant SS-31 and the ferroptosis inhibitor Fer-1 reversed the harm to the ovaries from co-exposure to PS-NPs and Cd, the aberrant expression of genes related to the SIRT3-SOD2/Gpx4 pathway was also improved. Our results suggested that co-exposure to PS-NPs and Cd may trigger ferroptosis by inhibiting the SIRT3-SOD2/Gpx4 pathway, leading to mitochondrial redox imbalance, which provided novel insights into reproductive toxicity due to the interaction of PS-NPs and Cd during adolescence.
纳米塑料（NPs）是一类新兴的污染物。它们可充当“特洛伊木马”，改变环境中重金属的生物利用度和毒性。然而，关于重金属与纳米塑料联合毒性的研究较少，尤其是在青春期这个关键发育阶段。在本研究中，将聚苯乙烯纳米塑料（PS-NPs）和/或镉（Cd）暴露于4周龄雌性大鼠28天，旨在探究PS-NPs和Cd联合暴露对青春期大鼠卵巢的潜在影响。结果表明，PS-NPs和Cd共同暴露加剧了大鼠的卵巢毒性，主要表现为闭锁卵泡数量增加和内分泌紊乱。进一步研究发现，PS-NPs和Cd协同抑制SIRT3-SOD2/Gpx4通路，诱导线粒体氧化应激和铁死亡，导致卵巢结构和功能受损。然而，添加线粒体靶向抗氧化剂SS-31和铁死亡抑制剂Fer-1可逆转PS-NPs和Cd共同暴露对卵巢的损害，与SIRT3-SOD2/Gpx4通路相关基因的异常表达也得到改善。我们的结果表明，PS-NPs和Cd共同暴露可能通过抑制SIRT3-SOD2/Gpx4通路触发铁死亡，导致线粒体氧化还原失衡，这为青春期PS-NPs和Cd相互作用引起的生殖毒性提供了新的见解。
