Beta-cypermethrin impairs reproductive function in male mice by inducing oxidative stress
Introduction
Cypermethrin (CYP) is a synthetic pyrethroid insecticide that has been widely used over the past 30 yr in China and other countries against pests, particularly Lepidoptera, cockroaches, and termites. In animals, cypermethrin has been used as a chemotherapeutic agent against ectoparasite infestations [1]. Beta-CYP is a mixture of the alpha and theta forms of the insecticide. Its activity is lower than that of alpha-CYP but higher than other CYPs. Beta-CYP has been applied widely for agricultural pest control in China and comprises more than 50% of the total pyrethroid market production [2]. Although cypermethrin was considered safe and was widely used on agricultural crops and forests as well as in public and animal health [3], there is accumulating evidence that chronic exposure or high-dose CYP has toxic effects on humans and animals.
Cypermethrin can be found in trace amounts or at higher concentrations in soil and air. In mammals, CYP can accumulate in body fat, skin, liver, kidneys, adrenal glands, ovaries, lung, blood, and heart [4], [5], [6]. However, the main target for CYP is the central nervous system. Symptoms of CYP toxicity in laboratory animals include pawing, burrowing, salivation, tremors, writhing, and seizures. In humans, high doses of CYP result in twitching, drowsiness, coma, and seizures [7]. Cypermethrin exerts its neurotoxic effect through voltage-dependent sodium channels and integral protein ATPases in the neuronal membrane [8], [9].
In addition to neurons, reproductive organs are another toxic target of CYP [10], [11]. Cypermethrin decreases the weight of testosterone-sensitive organs, increases the height of seminal gland epithelium, and reduces sperm count and motility in male mice [11], [12], [13], [14], [15]. Moreover, CYP significantly reduced serum concentrations of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) [11], in addition to decreasing the number of implantation sites and viable fetuses in females mated with these male mice [11]. Taken together, it is evident that CYP disrupted male reproductive function.
The mechanism by which CYP affects male reproduction is unclear: Pyrethroids are rapidly metabolized in mammals, and several studies have shown that CYP damages the brain, liver, and erythrocytes by causing oxidative stress [16], [17], [18]. However, there are no studies that have investigated how oxidative stress mediates CYP-induced deficits in male reproduction. Consequently, the current study examined the role of oxidative stress in beta-CYP–induced damage to the testes and the possible protective effects of vitamin E. Vitamin E is a fat-soluble vitamin with potent antioxidant properties that scavenges intracellular free radicals and maintains cell membrane integrity by inhibiting lipid peroxidation induced by reactive oxygen species (ROS) [19].
Section snippets
Materials
Beta-CYP (>99% pure) was obtained from Nanjing Panfeng Chem Ltd. (Nanjing, Jiangsu, China). The steroidogenic acute regulatory protein (StAR) antibody was kindly provided by Professor D.M. Stocco (Texas Tech University Science Center, Lubbock, TX, USA), and antibodies for phosphorylated (p)-ERK (E-4) and ERK were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA). The 125I-testosterone radioimmunoassay (RIA) kit was purchased from the China Institute of Atomic Energy (Beijing,
Effect of beta-CYP on body weight and testosterone-sensitive organ weights
The three doses of beta-CYP decreased body weight gain and weight of testosterone-sensitive organs, such as testes, epididymides, seminal vesicles, and prostate. These measures were reduced in mice given 10 or 20 mg/kg beta-CYP compared with that for the vehicle control (P < 0.05). Vitamin E ameliorated the effect of CYP; body and testosterone-sensitive organ weight was higher in the 20 mg/kg beta-CYP group that received vitamin E than that in the 20 mg/kg beta-CYP group that did not receive vitamin
Discussion
In this study, beta-CYP had profound negative effects on male reproductive function; however, these changes were prevented by administering an antioxidant. The high dose (20 mg/kg) of beta-CYP significantly reduced the weight of the reproductive organs including testes, epididymides, seminal vesicles, and prostate and diminished sperm number, development, and quality. Beta-CYP also reduced serum testosterone concentrations, possibly by reducing StAR expression and damaging the seminiferous
Acknowledgments
We thank Dr. Zhong-Xian Lu for his valuable and constructive criticism and Mr. J. Hodo Bedell for editorial assistance with the manuscript. This study was supported by a grant from the National Natural Science Foundation of China (No. 30270955).
References (52)
- et al.
Beta-cypermethrin resistance associated with high carboxylesterase activities in a strain of house fly, Musca domestica (Diptera: Muscidae)
Pestic Biochem Physiol
(2007) - et al.
The synaptosomal membrane bound ATPase as a target for the neurotoxic effects of pyrethroids, permethrin and cypermethrin
Chemosphere
(2003) Toxicology of selected pesticides, drugs, and chemicals. Short-chain alcohols
Vet Clin North Am Small Anim Pract
(1990)- et al.
Genotoxic effects of a synthetic pyrethroid insecticide, cypermethrin, in mice in vivo
Toxicol Lett
(1988) - et al.
Cypermethrin effects on the adult mice seminal glands
Ecotoxicol Environ Saf
(2009) - et al.
The role of reactive oxygen species in microcystin-LR-induced DNA damage
Toxicology
(2004) - et al.
Cypermethrin-induced oxidative stress in rat brain and liver is prevented by vitamin E or allopurinol
Toxicol Lett
(2001) - et al.
Lipid peroxidative damage on pyrethroid exposure and alterations in antioxidant status in rat erythrocytes: a possible involvement of reactive oxygen species
Toxicol Lett
(1999) - et al.
Effects of vitamin C and E on PCB (Aroclor 1254) induced oxidative stress, androgen binding protein and lactate in rat Sertoli cells
Reprod Toxicol
(2004) - et al.
Long-term cryopreservation of mouse sperm
Theriogenology
(2006)
Fresh and frozen-thawed sperm quality, nuclear DNA integrity, in vitro fertility, embryo development, and live-born offspring of N-ethyl-N-nitrosourea (ENU) mice
Cryobiology
Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction
Anal Biochem
Effects of prenatal stress on stress-induced changes in behavior and macrophage activity of mice
Physiol Behav
The antiandrogenic activity of pyrethroid pesticides cyfluthrin and beta-cyfluthrin
Reprod Toxicol
Vitamin C protects against in vitro cytotoxicity of cypermethrin in rat hepatocytes
Toxicol In Vitro
Effect of sodium nitroprusside on sperm motility, viability, and lipid peroxidation
Fertil Steril
Nitric oxide synthase inhibitor NG-monomethyl-L-arginine preserves sperm motility after swim-up
Fertil Steril
Effects of low concentrations of nitric oxide on the zona pellucida binding ability of human spermatozoa
Fertil Steril
Nitric oxide production of rat Leydig and Sertoli cells is stimulated by round spermatid factor(s)
Mol Cell Endocrinol
Bacterial lipopolysaccharide-induced oxidative stress in the impairment of steroidogenesis and spermatogenesis in rats
Reprod Toxicol
Vitamin E: beyond antioxidant function
Am J Clin Nutr
Gonzalez de Mejia E. alpha-Tocopherol modulates liver toxicity of the pyrethroid cypermethrin
Toxicol Lett
The mechanism of heat shock activation of ERK mitogen-activated protein kinases in the interleukin 3-dependent ProB cell line BaF3
J Biol Chem
Effects of cypermethrin on rainbow trout (Oncorhynchus mykiss)
Vet Med (Praha)
Effects of agricultural pesticides on humans, animals, and higher plants in developing countries
Arch Environ Health
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