Bisphenol a induces autophagy and apoptosis concurrently involving the Akt/mTOR pathway in testes of pubertal SD rats

Abstract

Bisphenol A (BPA), a typical endocrine disrupting chemical (EDC), has been proven to cause male reproductive toxicity. However, the precise mechanisms of this effect are still unclear. Puberty is a crucial period of reproductive development, and adolescents are more susceptible to xenobiotics. This research was designed to explore the mechanism of BPA toxicity on pubertal male reproduction. Rats were exposed to 0, 2, 10, 50 mg kg bw BPA, then the levels of sex hormones, oxidative stress, and semen quality were detected. HE staining, TUNEL assay and transmission electron microscopy were used to investigate the morphological changes, apoptosis, and autophagy in testes, respectively. Expressions of relevant genes and proteins were measured by RT-PCR, western blotting, and immunohistochemical staining. The results indicated that BPA exposure led to oxidative stress and endocrine disorders in pubertal male SD rats, caused apoptosis and autophagy in testes, and then damaged spermatogenesis ultimately. The Akt pathway was activated and the mTOR pathway was inhibited in the process. Taken together, BPA induced apoptosis and autophagy concurrently in pubertal testes, and this added a new layer to our understanding on male reproductive toxicity of BPA. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1977-1989, 2017.

Autophagie et spermatozoïde

“…Dans les spermatides matures, elle régule la vitalité et la mobilité des cellules [27]. Les conséquences environnementales et comportementales de l'autophagie sont de mieux en mieux comprises et ses implications sur la spermatogenèse commencent à être étudiées [41,42]. Une meilleure compréhension de la physiologie spermatique devrait permettre d'apporter des perspectives thérapeutiques pour les infertilités masculines encore étiquetées « idiopathiques » [43].…”

Contribution of Autophagy to the Physiological and Pathophysiological Functions in the Mammalian Testis

“…Meanwhile, the phosphorylation of AMPKa and the expression of p53 might act as a contributor to the upregulation of autophagy under BPA exposure. Of note, the expression of Beclin1 is not upregulated accompany by autophagy in testis under BPA exposure [67]. With NaF exposure, the autophagy is abnormally increased as evidenced by the synchronized increase of p62, suggesting that NaF exposure impairs autophagic machinery and result in the accumulation of autophagosomes in testis [68].…”

Disturbances in H+ dynamics during environmental carcinogenesis

“…As recently reviewed, a growing number of environmental pollutants are now known to interfere with autophagy [96]. Non-exhaustively, cadmium [97], arsenic [98], paraquat [99], bisphenol A [100], patulin [101] and TCDD [102,103], have been shown to differentially affect autophagy. Of particular interest here, two previous studies have also reported that B[a]P can modulate both autophagy [104] and mitophagy [105].…”