环境铅污染致雄性精子质量下降是铅毒性研究领域的重要问题，机制不明确。睾丸支持细胞产生的乳酸是精子发生过程中主要能源物质和抗凋亡因子。文献分析和前期实验基础提示铅睾丸细胞毒性涉及干扰细胞间乳酸转运，CD147协同单羧酸转运体（MCTs）介导细胞间乳酸穿梭可能是关键靶环节。本项目拟应用体外睾丸支持细胞-精母细胞非接触式共培养体系，观察低剂量铅暴露后细胞间乳酸水平变化及其与铅致精母细胞损伤的规律；铅对CD147-MCTs复合物共表达和功能的影响与乳酸穿梭的关系；采用调控技术获得CD147和MCTs不同表达水平细胞株，探讨CD147和MCTs表达水平变化对细胞内外乳酸含量的影响以及对铅细胞毒性的恶化或改善作用；构建睾丸局部CD147功能封闭的铅染毒动物模型，进一步在体内水平验证，最终在体内外水平明确CD147-MCTs 介导乳酸穿梭在调节铅暴露睾丸毒性中的作用。为铅生殖毒性防治提供新的靶点和依据。

Poor sperm quality caused by environmental lead pollution is an important problem. Its mechanism is not clear. In spermatogenesis, lactate is the central energy metabolite and anti-apoptotic factor. Lactate is produced by somatic Sertoli cells, and then utilized primarily by the germ cells. Analysis of the literature and our preliminary study prompted that the Pb-induced testicular toxicity involve in the interference of intracellular lactate transport. The intracellular lactate shuttle mediated by CD147 cooperation with the monocarboxylate transporter (MCTs), may be the key target. The objective of this study is to investigate the effect of CD147-MCTs mediated lactate shuttle in the improvement of testicular toxicity induced by low-dose lead exposure. We will determine that (1) the dose- and time-dependent effects of Pb treatment on lactate level and the expression levels of CD147, MCTs and CD147-MCTs in the Sertoli cells, spermatocytes and non contact co-culture system Sertoli cells and spermatocytes. (2) the relationship between the change of lactate level, CD147-MCTs expression levels and the toxic effect of lead on spermatocyte.（3）application of the cell lines with different expression levels of CD147 and MCTs obtained by biotechnology, and non contact co-culture system of Sertoli cells and spermatocytes, to analysis of the association between CD147-MCTs coexistence and activity with intracellular and extracellular lactate concentrations as well as the deterioration or improvement of lead toxicity. (4) to establish an animal model of lead exposure which CD147 function was blocked by anti-CD147 antibody in testis, and further verify the effect of CD147-MCTs mediated lactate shuttle on the improvement of testicular toxicity induced by lead exposure. The findings from this study will provide novel information for prevention and control of the male reproductive toxicity induced by lead.