title: 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.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Shu-Yun
authors.initials: SY
authors.lastname: Zhang
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanoshita
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yanagiba
authors.forename: Miya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Taya
authors.forename: ChunMei
authors.initials: C
authors.lastname: Li
authors.forename: Ai
authors.initials: A
authors.lastname: Okamura
authors.forename: Maiko
authors.initials: M
authors.lastname: Miyata
authors.forename: Jun
authors.initials: J
authors.lastname: Ueyama
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D004822:Epididymis / Q000166:cytology; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000502:physiology; D009929:Organ Size; D026023:Permethrin / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C463819:Bzrp protein, mouse; D007306:Insecticides; D010750:Phosphoproteins; D018079:Receptors, GABA; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D026023:Permethrin; D002784:Cholesterol; D015067:17-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006904:Hydroxymethylglutaryl-CoA Synthase