Permethrin May Disrupt Testosterone Biosynthesis via Mitochondrial Membrane Damage of Leydig Cells in Adult Male Mouse

Abstract

Permethrin, a popular synthetic pyrethroid insecticide used to control noxious insects in agriculture, forestry, households, horticulture, and public health throughout the world, poses risks of environmental exposure. Here we evaluate the reproductive toxicity of cis-permethrin in adult male ICR mice that were orally administered cis-permethrin (0, 35, or 70 mg/kg d) for 6 wk. Caudal epididymal sperm count and sperm motility in the treated groups were statistically reduced in a dose-dependent manner. Testicular testosterone production and plasma testosterone concentration were significantly and dose-dependently decreased with an increase in LH, and a significant regression was observed between testosterone levels and cis-permethrin residues in individual mice testes after exposure. However, no significant changes were observed in body weight, reproductive organ absolute and relative weights, sperm morphology, and plasma FSH concentration after cis-permethrin treatment. Moreover, cis-permethrin exposure significantly diminished the testicular mitochondrial mRNA expression levels of peripheral benzodiazepine receptor (PBR), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side-chain cleavage (P450scc) and enzyme and protein expression levels of StAR and P450scc. At the electron microscopic level, mitochondrial membrane damage was found in Leydig cells of the exposed mouse testis. Our results suggest that the insecticide permethrin may cause mitochondrial membrane impairment in Leydig cells and disrupt testosterone biosynthesis by diminishing the delivery of cholesterol into the mitochondria and decreasing the conversion of cholesterol to pregnenolone in the cells, thus reducing subsequent testosterone production.

Lambda Cyhalothrin Elicited Dose Response Toxicity on Haematological, Hepatic, Gonadal and Lipid Metabolic Biomarkers in Rat and Possible Modulatory Role of Taurine

“…5 Several investigations also reported that pesticides adversely affect the testicular functions in experimental animals [6][7][8][9] as well as they are potent endocrine disrupters. 10,11 Pesticides are responsible for oxidative stress that causes free radicals generation, leading to deoxyribonucleic acid (DNA) fragmentation. 12,13 Lambda-cyhalothrin (LCT), a type II pyrethroid pesticide, is used worldwide to control pests in a variety of agricultural crops.…”

Analysis and evaluation of pyrethroid exposure in human population based on biological monitoring of urinary pyrethroid metabolites

“…Recently, animal and in vitro studies suggest that some PYRs may disrupt the immune function, 50,51) produce oxidative stress, [52][53][54][55] and possess male reproductive toxicity by disrupting testosterone biosynthesis due to diminishing the delivery of cholesterol into the mitochondria and the conversion of cholesterol to pregnenolone in Leydig cells. 56) Moreover, it has been reported that the PYR metabolites, 3-PBAlc and 3-PBAld, possess estrogenic activity of approximately 10 5 less than that of 17b -estradiol. 57,58) These experimental data, although the tested dose was not necessarily low, could provide a new explanation for some of the findings observed in human studies.…”

Effect of Riboflavin Metabolites on Mitochondrial Electrochemistry

“…None of those inhibitors are electrochemically active in the potential window of the experiment (Blue line, Figures 1A, 1B and 1C). 24 However, although both of those inhibitors affect ubiquinone reduction of complex I, their electrochemical behavior are marginally different. As shown in Figure 1A, the inhibition of Complex I by permethrin resulted in an enhanced reduction wave and a diminished oxidation wave in cyclic voltammetry which is a function of the mitochondrial bioelectrocatalytic response toward the inhibition of ubiquinone reduction.…”