Assessment of male reproductive dysfunction induced by oral subchronic exposure to heavy metals in Sprague Dawley rats

Abstract

Increase in male factor infertility is a rapidly emerging concern throughout the world, while in Asia alone, 37% of the couple infertility cases have been attributed to the male factor. Among the causes driving this reduction in male fertility are environmental pollutants, including heavy metals. Because of their extensive usage in many industrial productions, the environment is excessively exposed to heavy metals. The current study was designed to assess and compare reproductive toxicity of lead, cadmium, and arsenic in male rats, using doses simulating both environmental and occupational exposure. Stock solution of each metal, 2.25 and 250mg/kg of lead, 1 and 5mg/kg of cadmium, and 2.5 and 40mg/kg of arsenic were prepared. In the current study adult male Sprague Dawley rats (n= 35) were divided into seven groups. First group served as control and received distilled water by oral gavage. Second and third groups received low and high dose of lead acetate while the other four groups received contrasting doses of cadmium chloride and sodium arsenite for twenty eight days. Body weight and glucose level was checked at 1st, 14th and 28th day of the experiment. Animals were sacrificed at day 29 post treatment. Testicular tissue and blood samples were taken for histology and biochemical analysis. Lead acetate (250mg/kg), cadmium chloride (5mg/kg) and sodium arsenite (40mg/kg) caused significant decline in body weight, testicular and epididymal weight, while the animals exposed to low doses of lead acetate and cadmium chloride depicted less pronounced effect on body and reproductive organ weight when compared to control. Exposure to high doses of each metal led to significant decline in plasma and intratesticular testosterone concentration, however this decline was less marked in animals treated with low doses of each metal respectively. Histomorphological studies showed significant degenerative alterations in rat testes in animals treated with high dose of each metal, but with more pronounced effect in cadmium (5mg/kg) treated rats as compared to low dose groups of each metal, and high dose groups of lead and arsenic. The results of current study indicate that exposure to high dose heavy metals caused pronounced reproductive toxicity in adult rats’ testis as compared to low doses. Furthermore, exposure to cadmium produced more prominent effect on rats’ testes, even at lower dose, as compared to damage induced by lead and arsenic. It can be preconcluded that this toxicity might be due to higher cellular toxicity and endocrine disrupting capability of cadmium, mediated through multiple molecular pathways.