Department of Pathology, Medical School, Xi'an Jiaotong University, Xi'an, 710061, China; Institute of Genetics and Developmental Biology, Medical School, Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Science and Education, Xi'an Children' s Hospital, Xi'an, Shaanxi, 710003, China.
Food Chem Toxicol. 2021 Sep;155:112409. doi: 10.1016/j.fct.2021.112409. Epub 2021 Jul 12.
Although circular RNAs (circRNAs) can function as microRNAs (miRNAs) sponges to participate in spermatogenesis, little is known about the functions of circRNAs in testis exposed to formaldehyde. In this study, twenty-four male SD rats (6-8 weeks) were randomly assigned to four groups, including a control group, 0.5, 2.46, and 5 mg/m formaldehyde exposure groups, inhaling formaldehyde for eight consecutive weeks. The RT-qPCR was used to detect the expression of rno_circRNA_016194; the testicular injuries were observed by testicular histopathology. Our study illustrated up-regulated rno_circRNA_016194 was dose-dependent with formaldehyde. Simultaneously, the testicular histopathology showed an obvious damages in the 2.46 and 5 mg/m formaldehyde exposure rats. Combined with bioinformatics analysis, the rno-miR-449a-5p was predicted and verified that its expression decreased in the testis exposed to formaldehyde. Meanwhile, the testicular morphometry changes were contrary to the expression of rno_circRNA_016194 and consistent with rno-miR-449a-5p. Moreover, bioinformatics analysis also prompted the potential downstream target gene for rno_circRNA_016194/rno-miR-449a-5p was Atg4b, and Atg4b expression was up-regulated in rats exposed to formaldehyde verifying by Western blot. Collectively, the rno_circRNA_016194 might be involved in formaldehyde-induced male reproductive toxicity and become potential therapeutic targets for male occupational exposure to formaldehyde.
尽管环状 RNA（circRNAs）可以作为 microRNAs（miRNAs）的海绵参与精子发生，但关于circRNAs 在暴露于甲醛的睾丸中的功能知之甚少。在这项研究中，将 24 只雄性 SD 大鼠（6-8 周龄）随机分为四组，包括对照组、0.5、2.46 和 5mg/m3 甲醛暴露组，连续吸入甲醛 8 周。使用 RT-qPCR 检测 rno_circRNA_016194 的表达；通过睾丸组织病理学观察睾丸损伤。我们的研究表明 rno_circRNA_016194 的表达随甲醛呈剂量依赖性上调。同时，2.46 和 5mg/m3 甲醛暴露组的睾丸组织病理学显示出明显的损伤。结合生物信息学分析，预测并验证了 rno-miR-449a-5p 在暴露于甲醛的睾丸中表达降低。同时，睾丸形态计量学的变化与 rno_circRNA_016194 的表达相反，与 rno-miR-449a-5p 的表达一致。此外，生物信息学分析还提示 rno_circRNA_016194/rno-miR-449a-5p 的潜在下游靶基因可能是 Atg4b，并且通过 Western blot 验证了 Atg4b 在暴露于甲醛的大鼠中表达上调。总之，rno_circRNA_016194 可能参与甲醛诱导的男性生殖毒性，并成为男性职业暴露于甲醛的潜在治疗靶点。
