MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
School of Public Health, Shanghai Jiao Tong University, Shanghai, 200025, China.
Environ Pollut. 2023 Nov 15;337:122468. doi: 10.1016/j.envpol.2023.122468. Epub 2023 Aug 29.
Today's women of childbearing age with a history of high lead (Pb) exposure in childhood have large Pb body burdens, which increases Pb release during pregnancy by promoting bone Pb mobilisation. The purpose of this study was to investigate the metabolic mechanisms underlying bone Pb mobilisation and explore the bone metabolism-related pathways during pregnancy. Drinking water containing 0.05% sodium acetate or Pb acetate was provided to weaned female rats for 4 weeks followed by a 4-week washout period, and then rats were co-caged with healthy males of the same age until pregnancy. Blood and bone tissues of the female rats were collected at gestational day (GD) 3 (early pregnancy), GD 10 (middle pregnancy), and GD 17 (late pregnancy), respectively. Pb and calcium concentrations, biomarkers for bone turnover, bone microstructure, serum metabolomics, and metabolic indicators were intensively analyzed. The results demonstrated that pre-pregnancy Pb exposure elevated blood lead levels (BLLs) at GD17, accompanied by a negative correlation between BLLs and trabecular bone Pb levels. Meanwhile, Pb-exposed rats had low bone mass and aberrant bone architecture with a larger number of mature osteoclasts (OCs) compared to the control group. Moreover, the metabolomics uncovered that Pb exposure caused mitochondrial dysfunction, such as enhanced oxidative stress and inflammatory response, and suppressed energy metabolism. Additionally, the levels of ROS, MDA, IL-1β, and IL-18 involved in redox and inflammatory pathways of bone tissues were significantly increased in the Pb-exposed group, while antioxidant SOD and energy metabolism-related indicators including ATP levels, Na-K-ATPase, and Ca-Mg-ATPase activities were significantly decreased. In conclusion, pre-pregnancy Pb exposure promotes bone Pb mobilisation and affects bone microstructure in the third trimester of pregnancy, which may be attributed to OC activation and mitochondrial dysfunction.
今天，有童年高铅（Pb）暴露史的育龄妇女体内有大量的 Pb 负荷，这会通过促进骨 Pb 动员来增加妊娠期间的 Pb 释放。本研究旨在探讨骨 Pb 动员的代谢机制，并探讨妊娠期间与骨代谢相关的途径。给断奶雌性大鼠饮用含 0.05%醋酸钠或醋酸铅的水 4 周，然后进行 4 周的洗脱期，然后与同龄健康雄性大鼠合笼直至怀孕。分别在妊娠第 3 天（孕早期）、第 10 天（孕中期）和第 17 天（孕晚期）收集雌性大鼠的血液和骨组织。深入分析 Pb 和钙浓度、骨转换生物标志物、骨微结构、血清代谢组学和代谢指标。结果表明，妊娠前 Pb 暴露使 GD17 的 BLL 升高，同时 BLL 与小梁骨 Pb 水平呈负相关。此外，与对照组相比，Pb 暴露组的大鼠骨量较低，骨结构异常，成熟破骨细胞（OC）数量较多。此外，代谢组学发现 Pb 暴露导致线粒体功能障碍，如增强氧化应激和炎症反应，抑制能量代谢。此外，Pb 暴露组骨组织中涉及氧化还原和炎症途径的 ROS、MDA、IL-1β 和 IL-18 水平显著升高，而抗氧化 SOD 和能量代谢相关指标，包括 ATP 水平、Na-K-ATP 酶和 Ca-Mg-ATP 酶活性均显著降低。总之，妊娠前 Pb 暴露会促进骨 Pb 动员，并影响妊娠晚期的骨微结构，这可能归因于 OC 激活和线粒体功能障碍。
