Co-exposure to arsenic and nickel induces oxidative stress and mineral imbalance, impairing male reproductive parameters in Wistar rats

Simultaneous exposure to multiple toxic metals is a common scenario in environmental contamination. Among these metals, arsenic and nickel are widely distributed pollutants with well-established toxic effects. However, their combined impact on male reproductive physiology and micromineral homeostasis remains poorly understood. This study evaluated the effects of subchronic co-exposure to arsenic (1 mg L^-1) and nickel (7 mg L^-1) in drinking water for 70 days on the hypothalamus, testis, and epididymis of adult Wistar rats. Exposed rats showed arsenic and nickel retention in all analyzed tissues, low serum testosterone levels, and alterations in the proportion of chemical elements, including copper, zinc, calcium, iron, and manganese. These findings were associated with an antioxidant enzyme dysregulation and high generation of protein carbonyls and nitric oxide in testicular and epididymal tissues, respectively. Consequently, the testes of co-exposed rats exhibited alterations in stereological and morphometric parameters, low daily sperm production, and initial histological changes in response to the toxic metals' presence. The hypothalamus exhibited focal areas of neuronal degeneration, especially in co-exposed rats. The epididymis of co-exposed animals presented focal areas of inflammatory infiltrates and germ cells within the luminal duct, with an acceleration of sperm transit time. Spermatozoa from all exposed rats showed low motility and high morphological abnormalities in the head, while the co-exposure increased the occurrence of midpiece and tail defects. These findings highlight the synergistic toxicity of arsenic and nickel on the male reproductive system after subchronic exposure, with a direct role of bioaccumulation and trace element dysregulation.