Toxic effects of allethrin on the male reproductive system

Abstract

Over the past decades, there has been an increased concern about the impact of environmental contaminants like pesticides on human reproductive system. These pesticides are used for both agricultural and non-agricultural purposes throughout the world. Synthetic pyrethroids persist in the environment and can enter into the geological cycle which can influence reproductive health. Allethrin, the first synthetic pyrethroid, which knock down insects has neurological effects and no reports are available about the impact on male reproductive system. In the present study, we studied the toxic effects of allethrin on male reproductive system using rat as a model system. We identified the molecular mechanism of allethrin cytotoxicity in rat Leydig cell carcinoma cells (LC540). Allethrin shows cytotoxicity in a concentration dependent manner. It increases lipid peroxidation and alters antioxidant enzyme status. Morphological analyses of LC540 cells treated with allethrin revealed the presence of apoptotic bodies. Using flow cytometry, we observed that the number of cells that displayed early apoptotic features and entering into G0 phase of cell cycle increased significantly with loss of mitochondrial membrane potential. The levels of p53 mRNA and cleaved PARP-1 protein were increased, whereas BCL-2, pro-Caspase-3 and PARP- 1 were decreased. Allethrin induced apoptosis was associated with voltage gated calcium channel mediated intracellular calcium release. Besides cytotoxicity, the reduced expression of spermatogenic factors namely Tgf-β1 and Scf suggests the potential of allethrin to affect spermatogenesis