Abstract
Many studies have revealed the hazardous effects of cigarette smoking and nicotine exposure on male fertility, but the actual, underlying molecular mechanism remains relatively unclear. To evaluate the detrimental effects of nicotine exposure on the sperm maturation process, two-dimensional gel electrophoresis and mass spectrometry analyses were performed to screen and identify differentially expressed proteins from the epididymal tissue of mice exposed to nicotine. Data mining analysis indicated that 15 identified proteins were mainly involved in the molecular transportation process and the polyol pathway, indicating impaired epididymal secretory functions. Experiments in vitro confirmed that nicotine inhibited tyrosine phosphorylation levels in capacitated spermatozoa via the downregulated seminal fructose concentration. Sord, a key gene encoding sorbitol dehydrogenase, was further investigated to reveal that nicotine induced hyper-methylation of the promoter region of this gene. Nicotine-induced reduced expression of Sord could be involved in impaired secretory functions of the epididymis and thus prevent the sperm from undergoing proper maturation and capacitation, although further experiments are needed to confirm this hypothesis.