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.

Highlights

  • At present, the toxic effects of arsenic exposure on the male reproductive system have been documented

  • The arsenic concentration in serum ranged from 0.18 to 0.67 μg/mL, while it ranged from 0.35 to 1.74 μg/g in testis tissue. These results suggest that arsenic can pass through the blood-testis barrier and accumulate in rat testis, which may subsequently induce a variety of adverse effects on male reproduction

  • Metabolites and the involved pathways in biological systems that are affected by and respond to environmental stresses using global profiling technologies, toxicoproteomics and toxicometabolomics are helpful to augment our understanding of the toxic mechanisms associated with arsenic exposure

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Summary

Introduction

The toxic effects of arsenic exposure on the male reproductive system have been documented. Arsenic was demonstrated to impair the development of reproductive organs, inhibit steroidogenesis and reduce sperm quality, which may result in male infertility These toxic effects are frequently attributed to the oxidative stress induced by excess reactive oxygen species (ROS), which causes lipids, proteins, and DNA damage[9,10,11]. By analyzing the differential urinary metabolome of infertile men in comparison to the control, Shen et al found that arsenic may exert toxicity via oxidative stress and sexual hormone disruption, as indicated by related metabolic biomarkers[16]. The results will be helpful to gain comprehensive insights into the mechanisms regarding arsenic-induced male reproductive toxicity, and to develop potential biomarkers for the health risk assessment of environmental arsenic exposure

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