Cypermethrin inhibits Leydig cell development and function in pubertal rats

Cypermethrin is a broad-spectrum pyrethroid insecticide that is widely used. It may induce adverse endocrine-disrupting effects on the male reproductive system. Whether cypermethrin can disrupt Leydig cell development and function in the late puberty remains elusive. The objective of this study was to explore the effect of cypermethrin exposure to male rats on the development and function of Leydig cells in late puberty and explore the underlying mechanism. Thirty-six male Sprague-Dawley rats (age of 35 days) were gavaged with cypermethrin (0, 12.5, 25, and 50 mg/kg/day) from postnatal day 35-49. Cypermethrin significantly lowered serum testosterone level while elevating serum luteinizing hormone level at a dose of 50 mg/kg, without altering serum follicle-stimulating hormone level. Cypermethrin markedly decreased CYP11A1-positive Leydig cell number at 50 mg/kg without affecting SOX9-positive Sertoli cell number. It significantly down-regulated the expression of Leydig cell genes, Lhcgr, Star, Cyp11a1, and Cyp17a1 and their proteins, while up-regulating the expression of Sertoli cell genes, Dhh and Amh, and their proteins, at doses of 12.5-50 mg/kg. In addition, cypermethrin significantly increased malondialdehyde level while lowering the expression of Sod1 and Sod2 and their proteins at 50 mg/kg. Cypermethrin markedly induced reactive oxidative species at a concentration of 200 μM and reduced mitochondrial membrane potential at 25 μM and higher concentrations after 24 h of treatment to primary Leydig cells in vitro. In conclusion, cypermethrin inhibits the development and function of Leydig cells in male rats in late puberty.