Study On The Toxic Mechanism Of Damage Induced By Cadmium In Leydig Cells

Cadmium (Cd) is toxic to Leydig cells, which directly decreases testosterone secretion, but its mechanism is still poorly understood. To further explore the signal pathway of toxicity caused by Cd, different concentrations (IC25, IC50 and IC75) of Cd were exposed to R2C cells for 24 h; 2DE-based proteomics was used to analyze the altered expression of proteins in the present study. Results indicated that Cd significantly reduced the production of progesterone and mitochondrial membrane potential (△Ψm) in a dose dependent manner; using 2DE-based proteomics technology,32 protein spots with altered expression were identified, and dihydrolipoamide dehydrogenase (DLD) was hubs in the network of proteins with altered expression; DLD showed down-regulation in mRNA and protein levels,which validated by real time RT-PCR and Western blot; Intracellular levels of cAMP also decreased in a dose dependent manner. The results highlight that DLD and cAMP may be key elements indicating the toxicity of Cd, and involved in the mechanism of damage in vivo. These findings also suggest that DLD may be one of the initial steps in the signaling steroidogenic pathway, which is located prior to cAMP. This mechanism likely contributed to a host of pathophysiological events especially for Androgen Deficiency in Aging Male (PADAM) and Male hypogonadism.