Review on mechanisms and therapeutic advances in inorganic arsenic-induced reproductive system disorders

Inorganic arsenic (iAs), a toxic metalloid and recognized carcinogen, is widely distributed in the natural environment. Human exposure to iAs occurs via multiple pathways, leading to its accumulation and adverse effects on the human body. iAs disrupt various signaling pathways, including the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, and interferes with key enzymatic systems, resulting in oxidative stress, DNA damage, and inflammatory responses, thereby irreversibly damaging biological systems. Notably, iAs exposure has been linked to reproductive toxicity including testicular abnormalities, impaired spermatogenesis, disrupted oocyte maturation, and diminished ovarian reserve. Several agents, such as dimercaprol (BAL) and its derivatives, curcumin and N-acetylcysteine (NAC), have shown potential in mitigating reproductive toxicity induced by iAs. This review summarizes the environmental distribution and biotransformation of iAs, its mechanisms of reproductive toxicity, and emerging therapeutic strategies, providing valuable insights into global iAs pollution control and public health interventions.