Permethrin exposure during puberty has the potential to enantioselectively induce reproductive toxicity in mice

Permethrin (PM), as a chiral pesticide, has two asymmetric centers, resulting in two pairs of enantiomers. In China, the commercial formulation of PM contains four enantiomers. The enantiomer-specific activity for endocrine disruption in mice remains unclear. In the present study, the four individual PM enantiomers were separated by preparative HPLC. Then, three week-old male ICR mice (after maternal ablactation) were orally administered (+)-cis, (-)-cis, (+)-trans, and (-)-trans-PM separately daily for 3 weeks at doses of 0, 25, 50 and 100 mg/kg/day, respectively. The results showed that 100 mg/kg of (+)-cis, (-)-cis and (-)-trans-PM treatments resulted in serious testicular histopathological damage, decreases in testis weight and serum testosterone (T) concentrations. Moreover, the transcription status of some key genes involved in cholesterol synthesis and transport as well as T synthesis in the testes were also influenced selectively by PM enantiomers, especially by the (+)-cis-PM. Additionally, peripheral benzodiazepine receptor (PBR) and 17β-hydroxysteroid dehydrogenase (17β-HSD) mRNA levels decreased significantly in the (+)-cis-PM group regardless of the administrated doses, while steroidogenic acute regulatory protein (StAR) levels were significantly down-regulated by (+)-cis and (-)-trans-PM. Moreover, significant differences were mainly found in HMG-CoA reductase, PBR, StAR and 17β-HSD mRNA levels between different enantiomers. Combined with the effects on physiology, histopathology and the expression of genes related to T synthesis, (+)-cis-PM showed the greatest endocrine disruption activities, (-)-cis and (-)-trans-PM were moderate, while (+)-trans-PM exhibited the lowest. These results suggested significant PM enantioselectivity in the reproductive toxicity of mice during puberty exposure.