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


Zhang, S-Y, Y Ito, O Yamanoshita, Y Yanagiba, M Kobayashi, K Taya, C-M Li, A Okamura, M Miyata, J Ueyama, C-H Lee, M Kamijima and T Nakajima.
Endocrinology, in press.

This version published
online on
April 26, 2007
Submitted on November 13, 2006
Accepted on April
18, 2007

Shu-Yun Zhang, Yuki Ito, Osamu Yamanoshita, Yukie Yanagiba, Miya Kobayashi, Kazuyoshi Taya, Chun-Mei Li, Ai Okamura, Maiko Miyata, Jun Ueyama, Chul-Ho Lee, Michihiro Kamijima, and Tamie Nakajima*

Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; College of Human life and Environment, Kinjo Gakuin University, Nagoya 463-8521, Japan; Department of Basic Veterinary Science, the United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan; Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan; Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya 461-8673, Japan

* To whom correspondence should be addressed. E-mail:

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/day) 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 decreased with an increase in luteinizing hormone (LH) significantly and dose-dependently 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, reproductive organ absolute and relative weights, sperm morphology, and plasma follicle stimulating hormone (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) 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 insecticide permethrin may cause the 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.