Parabens enhance the calcium-dependent testicular mitochondrial permeability transition: Their relevance on the reproductive capacity in male animals.

Parabens, alkyl ester derivatives from p-hydroxybenzoic acid, are extensively used as antimicrobial preservatives. Nonetheless, due to its widespread and massive employment, several studies highlighted the association between parabens and alterations in the reproductive system. This study aimed to relate the adverse effect of the most commonly used parabens in testis mitochondria with male fertility. From all the parabens used, propyl and butyl were the ones that most negatively decreased the respiratory control ratio. In the case of butyl, inhibitions of 20% and 60% were observed, respectively, at the lowest and highest concentration, when compared to the control group. The membrane potential was only significantly affected by propyl (14%) and butyl (31%), and at a concentration of 250 µM. Succinate dehydrogenase, cytochrome c oxidase, and ATPase activities showed a nonsignificant decrease. Cytochrome c reductase, on the other hand, showed statistically significant inhibitions for both propyl (56%) and butylparaben (55%). The susceptibility to the mitochondrial permeability transition pore (MPTP) opening was increased by all parabens, although this increase was markedly significant for propyl and butyl. These results show that the susceptibility of mitochondria to parabens is dependent on the alkyl chain length and parabens hydrophobicity, and the main mitochondrial target is Complex II-III and MPTP. Hence, this study demonstrates the contribution of parabens exposition to the inhibition of testis mitochondrial function and their putative noxious effect on the male reproductive system.