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Spermiogenesis toxicity of imidacloprid in rats, possible role of CYP3A4
Guo-Ping Zhao1, Jin-Wang Li2, Fang-Wei Yang3
1Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China; Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China.
Abstract:
This study evaluated the adverse effects of low-dose imidacloprid (IMI) on the characteristics of sperm from male Wistar rats. Thirty mature male rats were equally divided into three groups and orally administered vehicle (Control Group), acceptable daily intake (ADI) concentration of IMI (Group 1), and IMI at a dose 10-fold that of the ADI (Group 2) for 90 days. The findings revealed that IMI caused abnormalities in sperm concentrations and morphologies, accompanied by an imbalance of the gonadal hormone testosterone. Histopathological damage and decrease of testosterone levels were observed in testes from rats treated with IMI. However, estradiol and gonadotropin levels were unchanged after IMI treatment. IMI inhibited the activity of cytochrome P450 3A4 (CYP3A4) and left itself existed in the organism of rats. The indicators relating to sperms and CYP3A4 activity were recovered when rats were co-treated with IMI and CYP3A4 inducer rifampicin together. These results indicated that low-dose IMI exposure caused sperm abnormalities through affecting on the spermiogenesis in testis. Inhibition of CYP3A4 activity by IMI largely contributed to its sperm toxicity. Thus, IMI exposure at doses close to real-world settings resulted in sperm toxicity on rats, which might be a potential risk factor for human reproductive diseases.
Insights
Low-dose imidacloprid (IMI) exposure caused sperm damage in rats by affecting testosterone and inhibiting CYP3A4 activity. These effects were reversed with a CYP3A4 inducer, suggesting a risk to reproductive health.
Area of Science:
- Toxicology
- Reproductive Biology
- Endocrinology
Background:
- Neonicotinoid insecticides like imidacloprid (IMI) are widely used globally.
- Potential adverse effects of IMI on male reproductive health require thorough investigation.
Purpose of the Study:
- To evaluate the impact of low-dose imidacloprid (IMI) exposure on sperm characteristics and reproductive parameters in male Wistar rats.
- To elucidate the underlying mechanisms of IMI-induced reproductive toxicity, focusing on hormonal balance and enzyme activity.
Main Methods:
- Male Wistar rats were exposed to vehicle, acceptable daily intake (ADI) of IMI, or 10x ADI of IMI for 90 days.
- Sperm concentration, morphology, testosterone levels, and testicular histopathology were assessed.
- Cytochrome P450 3A4 (CYP3A4) activity and its role in IMI toxicity were investigated using co-treatment with rifampicin.
Main Results:
- IMI exposure led to decreased sperm concentration, abnormal sperm morphology, and reduced testosterone levels.
- Testicular histopathology revealed damage in IMI-treated rats.
- IMI inhibited CYP3A4 activity, and co-treatment with rifampicin restored sperm parameters and CYP3A4 activity.
Conclusions:
- Low-dose IMI exposure induces sperm toxicity in rats, primarily through affecting spermatogenesis and testosterone levels.
- Inhibition of CYP3A4 activity by IMI is a significant contributor to its observed sperm toxicity.
- IMI exposure at environmentally relevant doses poses a potential risk to male reproductive health, possibly impacting human reproductive diseases.
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