Abstract
The xenoestrogens nonylphenols (NPs), which are materials used in the plastic polymer industry, are considered endocrine disruptors in a wide range of organisms. Studies have shown that human health problems, such as infertility and reproductive toxicology, are linked with NPs. However, the mechanism by which NPs interfere with male reproduction is not fully elucidated. Here, we found that 4-NP can result in male reproductive impairment and reduce androgen receptor (AR) protein levels in rat sertoli cells in vitro and in vivo. Moreover, we performed RNA sequencing to assess the differential expression of ceRNAs in rat primary sertoli cells treated with 4-NP. Bioinformatics methods, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database and ceRNA functional network analyses, were used to investigate the sequencing data and gain further understanding of the biological processes. Our analysis revealed a core set of mRNAs (Ar, Atf6 and Cbp), and circRNAs (circ673, circ1377, circ1789, and circPTEN) that were selected and validated by RT-qPCR. In addition, the head-to-tail splicing of circ673, circ1377, circ1789, and circPTEN was identified by Sanger sequencing. These findings provide the first insight into the ceRNA expression profiles of rat sertoli cells and reveal that ceRNAs participate in 4-NP-induced impairment of sertoli cell function, thereby indicating potential therapies for both reproductive toxicology and male infertility.
Highlights
Nonylphenols (NPs) are some of the most widely used synthetic xenoestrogens in laundry and dish detergents, textiles, plastics, pesticides, paper and personal care products
Compared with the seminiferous tubules in the control group, which contained the full complement of germ cells, those in the 4-NP-treated group had smaller diameters, and only morphologically normal sertoli cells and undifferentiated
It is well demonstrated that estrogen plays an important role in the maintenance of male reproduction and homeostasis under physiological Pentikainen et al (2000) and pathological conditions
Summary
Nonylphenols (NPs) are some of the most widely used synthetic xenoestrogens in laundry and dish detergents, textiles, plastics, pesticides, paper and personal care products. Considering that NPs are so widely used because of their numerous applications, humans are unavoidably exposed, most likely throughout their lifetimes. A study by the Centers for Disease Control and Prevention (CDC) detected NPs in the urine of >50% of Americans sampled in 2005 (Calafat et al, 2005). Another previous study showed that NPs can induce changes in the metabolism and secretion of endogenous hormones and increase the risk of numerous pathologies, including prostate cancer. NPs have attracted considerable attention due to their estrogenic potential as well as their ability to induce the development of diabetes Yu et al (2018), cancer Forte et al (2016), Gan et al (2014) and reproductive diseases (ElDakdoky and Helal, 2007). Adverse effects of NPs on male reproductive function have been
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