Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.
Medical Imaging Center, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.
Environ Toxicol. 2024 Jun;39(6):3314-3329. doi: 10.1002/tox.24182. Epub 2024 Mar 5.
Previous studies on the effects of microplastics (MPs) on bone in early development are limited. This study aimed to investigate the adverse effects of MPs on bone in young rats and the potential mechanism.
Three-week-old female rats were orally administered MPs for 28 days, and endoplasmic reticulum (ER) stress inhibitor salubrinal (SAL) and ER stress agonist tunicamycin (TM) were added to evaluate the effect of ER stress on toxicity of MPs. The indicators of growth and plasma markers of bone turnover were evaluated. Tibias were analyzed using micro-computed tomography (micro-CT). Histomorphological staining of growth plates was performed, and related gene expression of growth plate chondrocytes was tested.
After exposure of MPs, the rats had decreased growth, shortened tibial length, and altered blood calcium and phosphorus metabolism. Trabecular bone was sparse according to micro-CT inspection. In the growth plate, the thickness of proliferative zone substantial reduced while the thickness of hypertrophic zone increased significantly, and the chondrocytes were scarce and irregularly arranged according to tibial histological staining. The transcription of the ER stress-related genes BIP, PERK, ATF4, and CHOP dramatically increased, and the transcription factors involved in chondrocyte proliferation, differentiation, apoptosis, and matrix secretion were aberrant according to RT-qPCR and western blotting. Moreover, the addition of TM showed higher percentage of chondrocyte death. Administration of SAL alleviated all of the MPs-induced symptoms.
These results indicated that MPs could induce growth retardation and longitudinal bone damage in early development. The toxicity of MPs may attribute to induced ER stress and impaired essential processes of the endochondral ossification after MPs exposure.
此前关于微塑料 (MPs) 对早期发育期骨骼影响的研究有限。本研究旨在探讨 MPs 对幼鼠骨骼的不良影响及其潜在机制。
3 周龄雌性大鼠经口给予 MPs 28 天，添加内质网 (ER) 应激抑制剂 Salubrinal (SAL) 和 ER 应激激动剂衣霉素 (TM) 以评估 ER 应激对 MPs 毒性的影响。评估生长指标和血浆骨转换标志物。采用 micro-CT 分析胫骨。进行生长板组织形态学染色，并检测生长板软骨细胞的相关基因表达。
暴露于 MPs 后，大鼠生长受阻，胫骨长度缩短，血钙和血磷代谢改变。micro-CT 检查发现骨小梁稀疏。在生长板中，增殖带厚度显著减少，肥大带厚度明显增加，组织学染色显示软骨细胞稀少且排列不规则。与内质网应激相关的基因 BIP、PERK、ATF4 和 CHOP 的转录显著增加，涉及软骨细胞增殖、分化、凋亡和基质分泌的转录因子异常，根据 RT-qPCR 和 western blotting 结果。此外，TM 的添加显示出更高比例的软骨细胞死亡。SAL 的给药缓解了 MPs 引起的所有症状。
这些结果表明 MPs 可引起早期发育过程中的生长迟缓和长骨损伤。 MPs 的毒性可能归因于诱导内质网应激和 MPs 暴露后破坏软骨内骨化的基本过程。
