Aflatoxin B1 promotes autophagy associated with oxidative stress-related PI3K/AKT/mTOR signaling pathway in mice testis

Abstract

Aflatoxin B₁ (AFB₁) is a hazard environmental pollutants and the most toxic one of all the aflatoxins. AFB₁ can cause a serious impairment to testicular development and spermatogenesis, yet the underlying mechanisms remain inconclusive. Oxidative stress acts as a master mechanism of AFB₁ toxicity, and can promote autophagy. Abnormal autophagy resulted in testicular damage and spermatogenesis disorders. The objective of this study was to explore the effect of AFB₁ on autophagy in mice testis and its potential mechanisms. In this study, male mice were intragastrically administered with 0, 0.375, 0.75 or 1.5 mg/kg body weight AFB₁ for 30 days. We found that AFB₁ induced testicular damage, reduced serum testosterone level and impaired sperm quality accompanied with the elevation of oxidative stress and germ cell apoptosis. Interestingly, we observed increasing numbers of autophagosomes in AFB₁-exposed mice testis. Meanwhile, AFB₁ caused testis abnormal autophagy with the characterization of increased expressions of LC3, Beclin-1, Atg5 and p62. Furthermore, AFB₁ downregulated the expressions of PI3K, p-AKT and p-mTOR in mice testis. Taken together, our data indicated AFB₁ induced testicular damage and promoted autophagy, which were associated with oxidative stress-related PI3K/AKT/mTOR signaling pathway in mice testis.

Keywords: Aflatoxin B(1) (AFB(1)); Autophagy; Mice testis; Oxidative stress; PI3K/AKT/mTOR signaling pathway.