Abstract
Nonylphenol (NP) is an alkylphenol that is widely used in chemical manufacturing. Exposure to this toxic environmental contaminant has been shown to negatively affect the reproductive system. Herein, we evaluated the toxicity of NP in mouse testes, while using in vitro organ culture. Mouse testicular fragments (MTFs), derived from five-day postpartum neonatal mouse testes, were exposed to different concentrations of NP (1–50 μM) for 30 days. The results showed that NP impaired germ cell development and maintenance. Furthermore, NP significantly downregulated the transcript levels of both undifferentiated and differentiated germ cell marker genes relative to those in controls. In particular, a high dose of NP (50 µM) led to complete germ cell depletion and resulted in spermatogenic failure, despite the presence of Sertoli and Leydig cells. In addition, the mRNA expression of steroidogenic enzymes, such as steroidogenic acute regulatory protein (STAR), Cytochrome P450 Family 11 Subfamily A Member 1 (Cyp11α1), Cytochrome P450 17A1 (Cyp17α1), and androgen receptor (AR), increased with increasing concentration of NP. Conversely, the expression of estrogen receptor alpha (ESR1) and Cytochrome P450 family 19 subfamily A member 1 (Cyp19α1) in NP-exposed MTFs decreased when compared to that of the control. Taken together, this study demonstrates that NP has a negative effect on prepubertal spermatogenesis and germ cell maintenance and it disrupts steroidogenesis and induces hormonal imbalance in MTFs.
Highlights
Nonylphenol (NP) is an alkylphenol that is widely used in the manufacture of antioxidants, lubricating oil additives, textiles, and agriculture products, such as pesticides, emulsifiers, and dispersants [1]
To investigate the effects of NP on neonatal testis development, mouse testicular fragments (MTFs) that were derived from 5.5-day-old testes were cultured
Immunostaining was performed for common germ cell markers, including the meiotic markers Synaptonemal Complex Protein 3 (SYCP3), Vasa, and Dazl (Figure 1B,C), with IgG isotype being used as the negative control (Figure 1D)
Summary
Nonylphenol (NP) is an alkylphenol that is widely used in the manufacture of antioxidants, lubricating oil additives, textiles, and agriculture products, such as pesticides, emulsifiers, and dispersants [1]. NP is an endocrine disruptor that is capable of interfering with the normal functioning of hormones in various organisms [2,3] It has been detected in most water matrices in the environment, including ground- and drinking water. Studies in Japan and Italy reported the presence of NP in human breast milk in the range of 0.65–1.4 ng/g [11] and 13.4–56.3 ng/mL, respectively [12]. It is unclear how NP affects the human body, as data regarding the effects of NP exposure on human cells are limited. It has been shown to induce apoptosis and DNA damage in human keratocytes [14]
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