Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Fertil Steril. 2021 Jan;115(1):125-137. doi: 10.1016/j.fertnstert.2020.08.1398. Epub 2020 Oct 14.
To evaluate and compare the methylation pattern of Human Homeobox (HOX) clusters (A-D) and HOX cofactors in normal, eutopic, and ectopic endometrial tissues with ectopic and eutopic endometriosis organoids as advanced preclinical research models.
A chromatin immunoprecipitation (ChIP) array containing 84 genes was used to analyze methylation levels of HOX clusters (A-D) and HOX cofactors in normal, eutopic, and ectopic endometrial biopsy specimens as well as ectopic and eutopic endometriosis organoids.
Reproductive biomedicine and cell science research centers.
PATIENT(S): Nine healthy women without endometriosis (control) and 16 women diagnosed with endometriosis.
INTERVENTION(S): Ectopic endometrial lesions were obtained using a laparoscopic procedure, and eutopic and control endometrium biopsy specimens were obtained using pipelle sampling.
MAIN OUTCOME MEASURE(S): Methylation levels of HOX clusters (A-D) and HOX cofactors in eutopic and ectopic endometrial biopsy specimens, as well as eutopic and ectopic endometriosis organoids and normal endometrium.
RESULT(S): Most HOX clusters (A-D) and HOX cofactors showed methylation alterations in ectopic/eutopic endometrial tissues and ectopic/eutopic endometriosis organoids compared with normal endometrium. These methylation alterations had the same pattern in ectopic/eutopic tissue biopsy specimens and ectopic/eutopic endometriosis organoids in most genes. A contrariwise methylation pattern was observed in 28 of 84 genes in the ectopic/eutopic tissue biopsy specimens and ectopic/eutopic endometriosis organoids.
CONCLUSION(S): Because a conserved pattern of methylation alterations in endometriosis tissues and organoids was observed for most of the investigated genes (56 of 84), it can be concluded that endometriosis organoids maintain epigenetic changes. Therefore, our study suggests endometriosis organoids as a novel preclinical model to determine the epigenetic mechanisms that underlie endometriosis.
评估和比较人类同源盒（HOX）簇（A-D）和 HOX 辅助因子在正常、在位和异位子宫内膜组织中的甲基化模式，以及作为先进临床前研究模型的异位和在位子宫内膜器官。
使用包含 84 个基因的染色质免疫沉淀（ChIP）阵列分析正常、在位和异位子宫内膜活检标本以及异位和在位子宫内膜器官中的 HOX 簇（A-D）和 HOX 辅助因子的甲基化水平。
生殖生物医学和细胞科学研究中心。
患者（或样品）：9 名无子宫内膜异位症的健康女性（对照组）和 16 名诊断为子宫内膜异位症的女性。
使用腹腔镜手术获取异位子宫内膜病变，使用 pipelle 取样获取在位和对照子宫内膜活检标本。
在位和异位子宫内膜活检标本以及在位和异位子宫内膜器官中 HOX 簇（A-D）和 HOX 辅助因子的甲基化水平。
与正常子宫内膜相比，大多数 HOX 簇（A-D）和 HOX 辅助因子在异位/在位子宫内膜组织和异位/在位子宫内膜器官中表现出甲基化改变。这些甲基化改变在大多数基因中在异位/在位组织活检标本和异位/在位子宫内膜器官中具有相同的模式。在 84 个基因中的 28 个基因中观察到异位/在位组织活检标本和异位/在位子宫内膜器官中相反的甲基化模式。
由于在大多数研究基因（84 个中的 56 个）中观察到子宫内膜异位症组织和器官中甲基化改变的保守模式，可以得出结论，子宫内膜异位症器官保留了表观遗传变化。因此，我们的研究表明子宫内膜异位症器官是确定导致子宫内膜异位症的表观遗传机制的新型临床前模型。
