Effects of 4-Nonylphenol on spermatogenesis and induction of testicular apoptosis through oxidative stress-related pathways

Duan, Peng and Hu, Chunhui and Butler, Holly and Chen, Wei and Huang, Wenting and Tang, Sha and Zhou, Wei and Yuan, Meng and Shi, Yuqin and Martin, Francis Luke and Yang, Kedi (2016) Effects of 4-Nonylphenol on spermatogenesis and induction of testicular apoptosis through oxidative stress-related pathways. Reproductive Toxicology, 62. pp. 27-38. ISSN 0890-6238

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Abstract

This study tested the hypothesis that prepubertal exposure to 4-Nonylphenol (NP) affects reproductive function in male rats. Twenty-four rats at five-weeks-old were randomly divided into four groups and treated with NP at varying concentrations (0, 5, 20, and 60 mg/kg/2d) for thirty days by intra-peritoneal injection. 60 mg/kg NP induced spermatogenic degeneration and pronounced deficits in epididymal sperm count, motility and function, whereas potentially stimulatory effects were observed at 5 NP mg/kg. Moreover, 60 mg/kg NP resulted in a significant reduction in fructose, FSH and LH; induced apoptosis related to oxidative stress; inhibited mRNA and protein levels of Bcl-2 and PCNA; as well as the additional up-regulation of p53, Bax, Apaf-1, cytochrome c, cleaved-caspase-3, Fas and FasL expression. Our data suggest potentially hormetic effects of NP on spermatogenic function. High-dose NP impairs testicular development and function by reducing cell proliferation and inducing apoptosis involving oxidative stress-related p53-Bcl-2/Bax and −Fas/FasL pathways.