Exposure to Pb and Cd alters MCT4/CD147 expression and MCT4/CD147-dependent lactate transport in mice Sertoli cells cultured in vitro

Abstract

Sertoli cells (SCs) provide lactate as an energy substrate to develop germ cells during spermatogenesis. Lead (Pb) and cadmium (Cd) can induce SC toxicity. However, the mechanisms remain unclear. This study aimed to investigate the molecular mechanisms by which Pb and Cd alter lactate transport and production by SCs. Mouse SC line (15P-1 cells) were cultured in the absence and presence of lead acetate (PbAc, 1, 10, 20 and 30 μM) or cadmium chloride (CdCl2, 0.5, 5, 10 and 15 μM) for 24 h. The results showed that PbAc exposure significantly decreased lactate dehydrogenase (LDH) activity and mRNA level, intracellular and extracellular lactate, and MCT4 and CD147 protein levels but increased MCT4 and CD147 mRNA levels. However, PbAc did not alter the glucose uptake, glucose transporters 1 (GLUT1) and 3 (GLUT3) mRNA expression of SCs. Thus, PbAc mainly decreased lactate production by inhibiting LDH activity. In CdCl2-treated SCs, intracellular lactate content increased but extracellular lactate content decreased significantly, P < .05. The glucose uptake, LDH activity, and mRNA expression of GLUT1, GLUT3 and LDH, all significantly increased. But the mRNA and protein levels of MCT4 and CD147 significantly decreased. Moreover, the fluorescence intensity of co-localizations of the MCT4–CD147 complex dose-dependently decreased in the cell membrane. Thus, CdCl2 may reduce lactate export by suppressing MCT4 and CD147 expression. These results suggest that PbAc and CdCl2 disrupt lactate production and transport in mouse SCs by disturbing glycolysis or inhibiting MCT4–CD147 transporter expression and co-localizations.