Natural antioxidants mitigate heavy metal induced reproductive toxicity: prospective mechanisms and biomarkers

Heavy metals are harmful environmental pollutants that have attracted widespread attention, attributed to their health hazards to humans and animals. Due to the non-degradable property of heavy metals, organisms are inevitably exposed to heavy metals such as arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg). Several studies revealed that heavy metals can cause reproductive damage by the excessive production of reactive oxygen species (ROS), which exacerbates oxidative stress, inflammation, and endocrine disruption. Natural antioxidants, mainly polyphenols, carotenoids, and vitamins, have been shown to mitigate heavy metal-induced reproductive toxicity potentially. In this review, accumulated evidences on the influences of four non-essential heavy metals As, Cd, Pb, and Hg on both males and females reproductive system were established. The purpose of this review is to explore the potential mechanisms of the effects of heavy metals on reproductive function and point out the potential biomarkers of natural antioxidants interventions toward heavy metal-induced reproductive toxicity. Notably, increasing evidence proven that the regulations of hypothalamic-pituitary-gonadal axis, Nrf2, MAPK, or NF-κB pathways are the important mechanisms for the amelioration of heavy metal induced reproductive toxicity by natural antioxidants. It also provided a promising guidance for prevention and management of heavy metal-induced reproductive toxicity.