State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Ecotoxicol Environ Saf. 2022 Oct 15;245:114105. doi: 10.1016/j.ecoenv.2022.114105. Epub 2022 Sep 22.
Microplastics (MPs) pollution becomes an increasing concern and researchers keep exploring the health effects caused by MPs exposure. The ageing process in the environment significantly alters the physicochemical characteristics of MPs and subsequently affects their toxicities. The health effects of aged MPs exposure and the mechanism underlying are worthy of exploration. Polystyrene microplastics (PS-MPs) (with size less than 50 µm) were obtained by grinding and screening polystyrene materials. PS-MPs continued to be aged by ozone treatment (0.4 mg/min, 9 h). Both male and female C57BL/6 mice were orally exposed to 0 or 2 mg/kg/d aged PS-MPs for 28 days. Results showed that PS-MPs were found in liver, ovary and spleen of females and liver, testis and spleen of males in the aged PS-MPs group. Exposure to aged PS-MPs significantly decreased abdominal fat/body coefficient, the adipocyte size and the serum LDL-C level in females. Compared to the control, serum estradiol (E2) level, the mRNA expression levels of genes regulating E2 production (17β-hsd, 3β-hsd and Star) in ovary and the protein expression levels of E2 receptors (ERα, ERβ), AMPKα and p-AMPKα1 in liver increased significantly, and the mRNA expression levels of AMP-activated protein kinase (AMPK) downstream genes (Srebp-1c, Fas and Scd1) in liver decreased significantly in the female aged PS-MPs group. Liver metabolomic profiling showed that differential metabolites between female aged PS-MPs group and female control group were enriched in biotin metabolism and the level of biotin increased significantly in the female aged PS-MPs group. However, no significant changes were detected in males. These results indicated that aged PS-MPs exposure increased ovarian E2 production and activated the AMPK pathway in the liver which might inhibit liver lipid synthesis only in females. Our findings provide new insights into the potential sex-specific health effects of environmental MPs pollution.
微塑料（MPs）污染日益受到关注，研究人员不断探索 MPs 暴露所导致的健康影响。环境中的老化过程会显著改变 MPs 的物理化学特性，进而影响其毒性。因此，值得探索老化 MPs 暴露的健康影响及其潜在机制。通过研磨和筛选聚苯乙烯材料获得粒径小于 50μm 的聚苯乙烯微塑料（PS-MPs）。将 PS-MPs 用臭氧处理（0.4mg/min，9h）继续老化。雄性和雌性 C57BL/6 小鼠分别经口暴露于 0 或 2mg/kg/d 老化 PS-MPs 28 天。结果显示，老化 PS-MPs 可在雌性小鼠的肝脏、卵巢和脾脏以及雄性小鼠的肝脏、睾丸和脾脏中被检出。与对照组相比，雌性小鼠经口暴露于老化 PS-MPs 后，其腹部脂肪/体重系数、脂肪细胞大小和血清 LDL-C 水平降低。与对照组相比，雌性小鼠的血清雌二醇（E2）水平、卵巢中调节 E2 产生的基因（17β-hsd、3β-hsd 和 Star）的 mRNA 表达水平以及肝脏中 E2 受体（ERα、ERβ）、AMPKα 和 p-AMPKα1 的蛋白表达水平显著升高，而肝脏中 AMP 激活蛋白激酶（AMPK）下游基因（Srebp-1c、Fas 和 Scd1）的 mRNA 表达水平显著降低。肝脏代谢组学分析表明，雌性老化 PS-MPs 组与雌性对照组之间的差异代谢物富集于生物素代谢途径，且雌性老化 PS-MPs 组的生物素水平显著升高。然而，在雄性小鼠中未检测到显著变化。这些结果表明，老化 PS-MPs 暴露可增加卵巢 E2 的产生并激活肝脏中的 AMPK 通路，从而仅在雌性小鼠中抑制肝脏脂质合成。本研究结果为环境 MPs 污染的潜在性别特异性健康影响提供了新的见解。
