Mitochondrial malfunction-initiated Leydig cell premature senescence partially participates in 1-nitropyrene-evoked downregulation of steroidogenic synthases in testes

Serum testosterone (T) in males has been declining during the past decades. The previous reports found that 1-nitropyrene (1-NP) exposure suppressed testicular T synthesis. The purpose of the current study was to further explore whether premature senescence participates in 1-NP-triggered reduction of testicular T synthesis. Adult male mice were orally exposed to 1-NP (0, 100, and 500 μg/kg) daily for 14 days. Serum and testicular T contents were diminished in 1-NP-administered mice. Mitochondria-located steroidogenic synthases, including StAR, CYP11A1, and 3βHSD1, were downregulated in 1-NP-administered mouse testes and MLTC-1 cells. Mechanistically, 1-NP exposure increased acetylation modification of mitochondrial steroidogenic synthases by inhibiting the enzymatic activity of SIRT3, an NAD