Liu Wenjie, Wang Zhaokai, Hu Xiaopeng
School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, China.
Technical Innovation Center for Utilization of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, China.
Front Pharmacol. 2021 May 18;12:644204. doi: 10.3389/fphar.2021.644204. eCollection 2021.
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 and . 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 (, and ), and circRNAs (, , , and ) that were selected and validated by RT-qPCR. In addition, the head-to-tail splicing of , , , and 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.
壬基酚（NPs）这类异雌激素是塑料聚合物工业中使用的材料，在广泛的生物体中被视为内分泌干扰物。研究表明，诸如不育和生殖毒理学等人类健康问题与壬基酚有关。然而，壬基酚干扰雄性生殖的机制尚未完全阐明。在此，我们发现4-壬基酚可导致雄性生殖功能受损，并降低大鼠支持细胞中的雄激素受体（AR）蛋白水平。此外，我们进行了RNA测序，以评估用4-壬基酚处理的大鼠原代支持细胞中ceRNA的差异表达。使用生物信息学方法，如基因本体论（GO）、京都基因与基因组百科全书（KEGG）数据库和ceRNA功能网络分析，来研究测序数据，并进一步了解生物学过程。我们的分析揭示了一组核心的mRNA（、和）以及环状RNA（、、、和），它们通过RT-qPCR进行了筛选和验证。此外，通过桑格测序鉴定了、、、和的头对尾剪接。这些发现首次深入了解了大鼠支持细胞的ceRNA表达谱，并揭示ceRNA参与了4-壬基酚诱导的支持细胞功能损伤，从而为生殖毒理学和男性不育症指出了潜在的治疗方法。
