Department of Gynecology, Fourth Hospital, Hebei Medical University, Shijiazhuang, China.
Department of Molecular Biology, Hebei Medical University, Shijiazhuang, China.
Mol Reprod Dev. 2019 Jun;86(6):632-638. doi: 10.1002/mrd.23139. Epub 2019 Mar 13.
Studies have shown that aberrant expression of IL-12p40, which is encoded by the interleukin-12B (IL-12B) gene, may be involved in the development of endometriosis. In this study, we investigated the role of aberrant methylation of the IL-12B promoter region and its associated expression in the development of ovarian endometriosis. By using pyrosequencing, we analyzed the methylation level of the IL-12B promoter region in eutopic and ectopic endometrium of patients with ovarian endometriosis and normal endometrium of control women. The expression of IL-12B mRNA was detected by quantitative real-time PCR. The results showed that the methylation level of the IL-12B promoter region in ectopic and eutopic endometrium of patients with ovarian endometriosis was significantly lower than that in endometrium of women without endometriosis ( p < 0.001 and p = 0.041, respectively). In contrast, mRNA levels were significantly increased in ectopic and eutopic endometrium of patients with ovarian endometriosis compared to those in endometrium of women without endometriosis ( p < 0.001 and p = 0.042, respectively). Correlation analysis showed that the methylation level of the IL-12B promoter region was negatively correlated with mRNA levels of IL-12B ( p < 0.001). Our data suggested that aberrant methylation of the IL-12B promoter region may be responsible for aberrant IL-12B mRNA expression in endometrium tissue of women, which may be associated with the development of ovarian endometriosis in northern Chinese women.
研究表明,白细胞介素 12B(IL-12B)基因编码的 IL-12p40 异常表达可能与子宫内膜异位症的发生有关。本研究旨在探讨 IL-12B 启动子区异常甲基化及其相关表达在卵巢子宫内膜异位症发生中的作用。通过焦磷酸测序,我们分析了卵巢子宫内膜异位症患者在位和异位子宫内膜以及对照组正常子宫内膜中 IL-12B 启动子区的甲基化水平。采用实时定量 PCR 检测 IL-12B mRNA 的表达。结果显示,卵巢子宫内膜异位症患者在位和异位子宫内膜中 IL-12B 启动子区的甲基化水平明显低于无子宫内膜异位症患者的子宫内膜(p<0.001 和 p=0.041)。相反,卵巢子宫内膜异位症患者在位和异位子宫内膜中 IL-12B mRNA 的表达水平明显高于无子宫内膜异位症患者的子宫内膜(p<0.001 和 p=0.042)。相关性分析显示,IL-12B 启动子区的甲基化水平与 IL-12B mRNA 的表达水平呈负相关(p<0.001)。本研究数据提示,IL-12B 启动子区异常甲基化可能导致女性子宫内膜中 IL-12B mRNA 表达异常,这可能与中国北方女性卵巢子宫内膜异位症的发生有关。