Evaluation of testicular structure in mice after exposure to environmentally relevant doses of manganese during critical windows of development.

Despite being an essential trace element with great importance for vital metabolic activities, the manganese (Mn) can also cause damage to organ systems. However, data on the effect of this metal on the male reproductive system are limited, especially using relevant doses to human exposure. The present study aimed to evaluate and compare the effects of Mn exposure on the testicular structure of mice. Three experiments were conducted: (I) direct exposure to realistic doses (0.013, 0.13, and 1.3 mg/kg/day of MnCl); (II) parental and direct exposure to realistic doses (as in experiment I), where the animals were exposed during intrauterine development and from lactation until reproductive maturity; (III) direct exposure to high doses (15, 30, and 60 mg/kg/day of MnCl). Biometric, histopathological, histomorphometric and stereological parameters of the testis were evaluated, in addition to sperm morphology. Bioinformatic analyses were performed to identify potential Mn binding sites in 3β-HSD and P450ssc, as well as their protein-protein interaction network. The results obtained were compared using the integrated biomarker response index (IBR). There was an increase of seminiferous tubules pathologies in all experimental conditions tested, with effects on tubular volume, as well as a reduction in tubular diameter. The IBR analyses showed that parental and direct exposure had a significant negative effect on the testicular structure due to the exposure of this metal to sensitive periods of animal development. This study suggests that Mn has the potential to alter the morphological parameters of the testes, affecting the spermatogenesis in mice.