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

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 60mg/kg/2d) for thirty days by intra-peritoneal injection. 60mg/kg NP induced spermatogenic degeneration and pronounced deficits in epididymal sperm count, motility and function, whereas potentially stimulatory effects were observed at 5 NPmg/kg. Moreover, 60mg/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.

Roles of Fas/FasL-mediated apoptosis and inhibin B in the testicular dysfunction of rats with left-side varicocele

“…It is widely accepted that FasL expressed on Sertoli cells can initiate apoptosis in neighbouring germ cells that express Fas (Lee, Richburg, Shipp, Meistrich, & Boekelheide, ). The Fas/FasL system activates caspase‐8 and its downstream caspases such as caspase‐3 triggering programmed cell death (Huang et al., ).The activation of the Fas/FasL system by the varicocele may therefore have an important role in the apoptosis of both Sertoli cells and germ cells because our results demonstrated that the expression of Fas, FasL and caspase‐3 increased in response to the establishment of a varicocele, consentient with results of many other studies (Duan et al., ; Huang et al., ). As secretion of inhibin B involves both Sertoli cells and germ cells (Meachem et al., ), the activation of the Fas/FasL system in response to the presence of the varicocele would lead to apoptosis of both Sertoli cells and germ cells and consequently a decrease in inhibin B secretion.…”

4-Nonylphenol effects on rat testis and sertoli cells determined by spectrochemical techniques coupled with chemometric analysis

“…NP has been found in various human tissues (Deng et al, 2010;Asimakopoulos et al, 2012) and to cause a wide range of reproductive and developmental toxicities in fish and mammals (Chapin et al, 1999;El-Sayed Ali et al, 2014;Duan et al, 2016a;Duan et al, 2017b). Male reproductive system toxicity is one of the prominent adverse effects of NP (Noorimotlagh et al, 2017).…”

“…Evidence that NP could exert estrogenic actions and disturb hormonal homeostasis has arisen from studies in male rats models (Chapin et al, 1999;Duan et al, 2017a). Our previous studies found that pre-pubertal exposure to NP in rats induced reproductive dysfunction during adulthood (Duan et al, 2016a;Huang et al, 2016). NP treatment affects spermatogenesis, sperm function and morphology (El-Sayed Ali et al, 2014;Cheng et al, 2017;Duan et al, 2017a).…”

“…NP treatment affects spermatogenesis, sperm function and morphology (El-Sayed Ali et al, 2014;Cheng et al, 2017;Duan et al, 2017a). When treated with ≥50 mg NP/kg, the seminiferous tubules exhibit a hollow tendency and the levels of apoptosis of testicular cells increase (Duan et al, 2016a;Huang et al, 2016;Duan et al, 2017a). NP has been shown to trigger apoptosis and autophagy in Sertoli cells (Huang et al, 2016;Duan et al, 2017b;Su et al, 2018).…”

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells

“…Importantly, our previous study outlined that NP treatment triggers Sertoli cell (SC) autophagy, probably through the ROS-mediated AMPK-mTOR pathway (Duan et al 2016c). Additionally, NP exposure is shown to increase oxidative stress and germ cell apoptosis in testis, to cause seminiferous tubule degeneration and to reduce hormone secretion, consequently impairing sperm parameters, capacitation and morphology (Duan et al 2016a;Duan et al 2016b;Lu et al 2014;McClusky et al 2007). Although increasing evidence suggests that autophagy activity may play an important function in the pathogenesis of male reproductive toxicity (Han et al 2015), no information regarding NP effects on autophagy induction in vivo is currently available.…”