Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

Abstract

Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure

“…However, a significant increase was observed in the F2 and F3 generations of the arsenic lineage. Some studies have reported no change in testis weight 62 , 63 besides a decrease in the epididymis weight 64 after exposure to arsenic in rats, on the contrary, an increase in testicles and epididymis weight has also been reported 65 ; in this study, a decrease in the weight of the epididymis was observed in the F0 generation and an increase and decrease in the F2 and F3 generations, respectively, following the arsenic lineage. As far as we know, there is no evidence of the transgenerational effects of arsenic in the body weight and of various organs, also not related to exposures to other metals, at least in mammals, however, there is evidence related to another environmental toxicants.…”

α‐Lipoic acid inhibits testicular and epididymal oxidative damage and improves fertility efficacy in arsenic‐intoxicated rats

“…The dose selection and the time regimen for LA was selected on the basis of earlier reports . The concentration of SA was selected based on the studies of Huang et al . The concentration of SA (i.e., 25 mg/L) selected in this study contains approximately 14.4 mg/L of arsenic, which is also approximately equivalent to 2.3 mg/L of arsenic for humans .…”

Metabolic disturbance in hippocampus and liver of mice: A primary response to imidacloprid exposure

“…Metabolomics, acting as end points of gene expression and functional protein actions, provides a direct "functional readout of the physiological state" of an organism which facilitates to better understand the toxicant-induced responses and discover biomarkers 23,24 . Recently, a large number of literatures have described metabolomics studies in toxic effects induced by environmental pollutants, such as perfluorinated compounds 25,26 , pesticide residues 27,28 , heavy metals 29 , and nanoparticles 30 . Tufi et al 28 employed metabolomics to explore IMI-induced toxicity in the central nervous system of the freshwater snail and pointed out a disruption of neuronal metabolism.…”