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Imidacloprid disrupts the endocrine system by interacting with androgen receptor in male mice
Xianling Yuan1, Jiayan Shen1, Xinyue Zhang1
1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
Abstract:
In the current study, six-week-old male ICR mice were administered imidacloprid (IMI) at concentrations of 3, 10 and 30 mg/L for a duration of 10 weeks to investigate the toxicity of IMI on the endocrine system. We observed that testicular morphology was severely impaired and damaged, and the levels of serum testosterone (T) and the expression of androgen receptor (AR) decreased significantly. Molecular docking analysis suggested that IMI docks into the active site of AR successfully and that three key hydrogen bonds were formed with the active site residues Glu11, Gln41 and Lys138. The binding free energy value of the AR-IMI complex suggested a stable binding between IMI and AR. All these results indicated that IMI could interact with AR. In addition, major genes in the testis involved in the synthesis of cholesterol and T were generally inhibited, and the serum cholesterol sources were also reduced. Moreover, the aromatase in male mice was lacking after subchronic IMI exposure. The data acquired from the present study indicated that IMI could lead to endocrine disruption by interacting with AR and influence the expression of genes involved in the production of T in male mice.
Insights
Imidacloprid (IMI) exposure damages mouse testes and disrupts the endocrine system by binding to the androgen receptor (AR). This pesticide exposure significantly reduces testosterone levels and impacts cholesterol and aromatase, indicating endocrine disruption.
Area of Science:
- Endocrinology
- Toxicology
- Molecular Biology
Background:
- Imidacloprid (IMI) is a widely used insecticide.
- Concerns exist regarding its potential impact on the endocrine system and reproductive health.
Purpose of the Study:
- To investigate the toxic effects of subchronic imidacloprid exposure on the male endocrine system.
- To elucidate the molecular mechanisms underlying IMI-induced endocrine disruption.
Main Methods:
- Six-week-old male ICR mice were exposed to varying concentrations of IMI (3, 10, 30 mg/L) for 10 weeks.
- Evaluated testicular morphology, serum testosterone levels, and androgen receptor (AR) expression.
- Utilized molecular docking to analyze IMI binding to the AR active site.
- Assessed the expression of genes involved in cholesterol and testosterone synthesis, and aromatase activity.
Main Results:
- IMI exposure caused severe testicular damage and impaired morphology.
- Significant decreases in serum testosterone (T) levels and AR expression were observed.
- Molecular docking confirmed stable binding of IMI to the AR active site via hydrogen bonds.
- Inhibition of key genes in cholesterol and T synthesis pathways, alongside reduced aromatase activity.
Conclusions:
- Imidacloprid acts as an endocrine disruptor in male mice by interacting with the androgen receptor.
- IMI exposure negatively impacts testicular function and hormone production through AR binding and gene expression modulation.
- Findings highlight the potential risks of IMI to male reproductive health and endocrine balance.

