Abstract
Nonylphenol (NP) is an endocrine-disruptor chemical that negatively affects reproductive health. Testes exposure to NP results in testicular structure disruption and a reduction in testicular size and testosterone levels. However, the effects of NP on spermatogonia in testes have not been fully elucidated. In this study, the molecular mechanisms of NP in GC-1 spermatogonia (spg) cells were investigated. We found that cell viability significantly decreased and apoptosis increased in a dose-dependent manner when GC-1 spg cells were exposed to NP. Furthermore, the expression levels of the pro-apoptotic proteins increased, whereas anti-apoptosis markers decreased in NP-exposed GC-1 spg cells. We also found that NP increased reactive oxygen species (ROS) generation, suggesting that ROS-induced activation of the MAPK signaling pathway is the molecular mechanism of NP-induced apoptosis in GC-1 spg cells. Thus, NP could induce c-Jun phosphorylation; dose-dependent expression of JNK, MKK4, p53, and p38; and the subsequent inhibition of ERK1/2 and MEK1/2 phosphorylation. The genes involved in apoptosis and JNK signaling were also upregulated in GC-1 spg cells treated with NP compared to those in the controls. Our findings suggest that NP induces apoptosis through ROS/JNK signaling in GC-1 spg cells.
Highlights
Nonylphenol (NP) is a xenobiotic used in chemical manufacturing that can accumulate in the environment
Based on these previous results, we evaluated the effects of NP in vitro using the granulosa cells (GCs)-1 spg cell line, which was derived from 10-day-old mouse testes
To determine the cytotoxic effect of NP on the proliferation of GC-1 spg cells, a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure cell viability, which significantly decreased when the cells were exposed to 1–10 μM NP dissolved in 0.1% dimethyl sulfoxide (DMSO) for 24 h compared to the control group treated with 0.1% DMSO alone (Figure 1A)
Summary
Nonylphenol (NP) is a xenobiotic used in chemical manufacturing that can accumulate in the environment. Several studies have reported that EDCs induce ROS-mediated apoptosis. In Sertoli cells derived from 18–20-day-old male rats, NP treatment induced apoptosis via the ROS- mediated AMPK/Akt-mTOR and JNK pathways [29]. An in vivo study showed that BPA and NP induced rat germ cell apoptosis mediated by the activation of p38 MAPK and ADAM17 [31]. These and other studies have reported the toxic effects of NP in reproductive organs [8,16,30], the molecular mechanisms of NP toxicity in GC-1 spg cells have not been characterized in detail. We investigated the molecular mechanisms underlying NP-mediated toxicity in GC-1 spg cells
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