Nonylphenol induced apoptosis and autophagy involving the Akt/mTOR pathway in prepubertal Sprague-Dawley male rats in vivo and in vitro.

This research explores the detrimental effect of nonylphenol (NP) to prepubertal Sprague-Dawley male rats in vivo and in vitro. Herein, forty-two 3-week-old rats were randomly divided into six groups, which were treated with NP (0, NAC, 25, 50, 100, 100+NACmg/kg/2d for 30 consecutive days) by intraperitoneal injection. NP induced a reduction in testosterone (15.58%, 17.23%, 13.38% in 25, 50, 100mg/kg group, respectively), triggered apoptosis related to oxidative stress, and disturbed mRNA and/or protein levels of PI3K, PTEN, PDK1, p-Akt, p-mTOR, p70S6K, caspase-3, LC3B. NP induced morphological abnormality in epididymal sperm (2.00-, 3.02-fold in 50, 100mg/kg group, respectively). Pretreatment with NAC, attenuated NP-induced ROS production; recovered testosterone in serum, and ameliorated toxic effect in epididymal sperm. Sertoli cells were isolated, purified, treated with NP (0, 10, 20, and 30μM) for 12h. NP disturbed mRNA and/or protein levels of caspase-3, cleave-caspase-3, LC3B involving the PI3K/Akt/mTOR pathway. It also decreased protein levels of ABP, FSHR, N-cadherin, transferrin, vimentin; disturbed the gene levels of all, but vimentin. Pretreatment with wortmannin, alleviated an NP-induced reduction in protein levels of PI3K and PTEN. In conclusion, excess NP exposure induces apoptosis and autophagy, causes reproductive lesions involving the PI3K/AKT/mTOR pathway both in vivo and in vitro. It also triggers oxidative stress and hormonal deficiency, reduces semen quality.