Arsenic is one of the metalloid pollutants widespread in the environment. At present, its exposure and effects on human health, especially on male reproductive health have increasingly raised public concerns. Epidemiologic researches have demonstrated that the content of arsenic in men is significantly related to the reduced sperm quality. However, its underlying molecular mechanisms were far from being completely understood. Based on the evidence that histone methylation and acetylation play a pivotal role in spermatogenesis, and that arsenic exposure can change the status of histone modifications, by using the male rat model, this proposal plans to quantify the global methylation and acetylation levels of histone H3 and H4, and investigate the histone modification changes of specific gene promoter in rat sperms. In addition, by analyzing the arsenic content in serum of reproductive-aged male population, and the histone modification status in sperms with reference to the animal experimental results, we will explore the relationships of arsenic exposure-histone modification-sperm quality by statistics in combination with the clinical epidemiologic data, hoping to verify our toxicological hypothesis that arsenic can affect sperm quality by altering the status of sperm histone modification on population level, and reveal the molecular mechanisms of arsenic-mediated male reproductive toxicity.
