Effects of perfluoroundecanoic acid on the function of Leydig cells in adult male rats

Perfluoroundecanoic acid (PFUnA), a perfluorinated compound, has environmental persistence, bioaccumulation, and potential toxicity. However, its effect on Leydig cell function remains unclear. Rats (age of 56 days) were gavaged with 0 (corn oil), 0.1, 0.5, 1, or 5 mg/kg/day PFUnA for 28 days. PFUnA significantly reduced serum testosterone levels as low as 0.5 mg/kg. PFUnA markedly decreased Leydig cell number as low as 0.1 mg/kg. PFUnA markedly reduced transcript levels of Star and Insl3 in the testes at 1 mg/kg after adjusting to Leydig cell number. It also reduced their protein levels. PFUnA significantly decreased the phosphorylation of AKT1 and mTOR as low as 0.1 mg/kg and the phosphorylation of ERK1/2 at 1 mg/kg and the phosphorylation of AKT1, AKT2, ERK1/2, and mTOR in Leydig cells at various concentrations (0.01–10 μM) after 24 h of in vitro treatment. In conclusion, PFUnA inhibits Leydig cell function possibly via AKT/ERK1/2/mTOR signaling pathways. PFUnA exerts multiple mechanisms to inhibit Leydig cell (LC) function in rats. It inhibits LH secretion, leading to low phosphorylation of AKT1/AKT2, it also lowers AKT1, AKT2, ERK1/2, and mTOR phosphorylation, which results in the inhibition of LC function (lower testosterone synthesis). [Display omitted] •PFUnA significantly inhibits Leydig cell function in vivo.•PFUnA significantly decreases Leydig cell number in vivo.•PFUnA inhibits testosterone production by primary Leydig cells.•PFUnA reduces AKT1, ERK1/2, and mTOR signals in vivo and in vitro.