Mechanism and impact of heavy metal-aluminum (Al) toxicity on male reproduction: Therapeutic approaches with some phytochemicals

Heavy metals are ubiquitous environmental toxicants that have been known to have a serious effect on human and animal health. Aluminum (Al) is a widely distributed metal in nature. Al exposure has a detrimental impact on human fertility. This review focused on Al-induced male reproductive toxicity and the potential therapeutic approaches with some phytochemicals. Data from the literature showed that Al exposure is accompanied by a drastic decline in blood levels of FSH, LH, and testosterone, reduced sperm count, and affected sperm quality. Al exposure at high levels can cause oxidative stress by increasing ROS and RNS production, mediated mainly by downregulating Nrf2 signaling. Moreover, several investigations demonstrated that Al exposure evoked inflammation, evidenced by increased TNF-alpha and IL-6 levels. Additionally, substantial evidence concluded the key role of apoptosis in Al-induced testicular toxicity mediated by upregulating caspase-3 and downregulating Bcl2 protein. The damaging effects of Al on mitochondrial bioenergetics are thought to be due to the excessive generation of free radicals. This review helps to clarify the main mechanism involved in Al-associated testicular intoxication and the treatment strategy to attenuate the notable harmful effects on the male reproductive system. It will encourage clinical efforts to target the pathway involved in Al-associated testicular intoxication.