Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Environ Pollut. 2023 Nov 15;337:122613. doi: 10.1016/j.envpol.2023.122613. Epub 2023 Sep 26.
Large bone lead (Pb) resulting from high environmental exposure during childhood is an important source of endogenous Pb during pregnancy and lactation. Docosahexaenoic acid (DHA) attenuates Pb toxicity, however, the effect of DHA on bone Pb mobilisation during lactation has not been investigated. We aimed to study the effects of DHA supplementation during pregnancy and lactation on bone Pb mobilisation during lactation and its potential mechanisms. Weaning female rats were randomly divided into control (0.05% sodium acetate) and Pb-exposed (0.05% Pb acetate) groups, after a 4-week exposure by ad libitum drinking and a subsequent 4-week washout period, all female rats were mated with healthy males until pregnancy. Then exposed rats were randomly divided into Pb and Pb + DHA groups, and the latter was given a 0.14% DHA diet, while the remaining groups were given normal feed until the end of lactation. Pb and calcium levels, bone microarchitecture, bone turnover markers, mitochondrial function and serum metabolomics were analyzed. The results showed that higher blood and bone Pb levels were observed in the Pb group compared to the control, and there was a significant negative correlation between blood and bone Pb. Also, Pb increased trabecular bone loss along with slightly elevated serum C-telopeptide of type I collagen (CTX-I) levels. However, DHA reduced CTX-I levels and improved trabecular bone microarchitecture. Metabolomics showed that Pb affected mitochondrial function, which was further demonstrated in bone tissue by significant reductions in ATP levels, Na-K-ATPase, Ca-Mg-ATPase and CAT activities, and elevated levels of MDA, IL-1β and IL-18. However, these alterations were partially mitigated by DHA. In conclusion, DHA supplementation during pregnancy and lactation improved bone Pb mobilisation and mitochondrial dysfunction in lactating rats induced by pre-pregnancy Pb exposure, providing potential means of mitigating bone Pb mobilisation levels during lactation, but the mechanism still needs further study.
孕期高环境铅暴露导致的大骨铅是妊娠和哺乳期内源性铅的重要来源。二十二碳六烯酸（DHA）可减轻铅毒性，但 DHA 对哺乳期骨铅动员的影响尚未得到研究。我们旨在研究孕期和哺乳期补充 DHA 对哺乳期骨铅动员及其潜在机制的影响。我们将断奶雌性大鼠随机分为对照组（0.05%醋酸钠）和 Pb 暴露组（0.05%醋酸铅），通过自由饮用暴露 4 周，随后进行 4 周洗脱期，所有雌性大鼠与健康雄性大鼠交配直至怀孕。然后将暴露组大鼠随机分为 Pb 组和 Pb+DHA 组，后者给予 0.14%DHA 饮食，而其余组给予正常饲料直至哺乳期结束。分析 Pb 和钙水平、骨微结构、骨转换标志物、线粒体功能和血清代谢组学。结果显示，Pb 组的血铅和骨铅水平均高于对照组，且血铅和骨铅呈显著负相关。此外，Pb 增加了小梁骨丢失，同时血清 I 型胶原 C-末端肽（CTX-I）水平略有升高。然而，DHA 降低了 CTX-I 水平并改善了小梁骨微结构。代谢组学显示，Pb 影响了线粒体功能，这在骨组织中进一步通过显著降低 ATP 水平、Na-K-ATP 酶、Ca-Mg-ATP 酶和 CAT 活性，以及升高 MDA、IL-1β 和 IL-18 水平来证明。然而，这些改变部分被 DHA 缓解。综上所述，孕期和哺乳期补充 DHA 可改善孕前 Pb 暴露致哺乳期大鼠骨铅动员和线粒体功能障碍，为减轻哺乳期骨铅动员水平提供了潜在手段，但机制仍需进一步研究。
