Effects of high progesterone level on the day of human chorionic gonadotrophin administration in in vitro fertilization cycles on epigenetic modification of endometrium in the peri-implantation period
Effects of high progesterone level on the day of human chorionic gonadotrophin administration in in vitro fertilization cycles on epigenetic modification of endometrium in the peri-implantation period
复制标题
体外受精周期中人绒毛膜促性腺激素给药日高孕酮水平对围着床期子宫内膜表观遗传修饰的影响
DOI：
10.1016/j.fertnstert.2017.06.004
复制
发表时间：
2017-08-01
影响因子：
6.7
通讯作者：
Zhang, Songying
中科院分区：
文献类型：
--
作者：
Xiong, Yujing;Wang, Jianzhang;Zhang, Songying
目的：探讨体外受精（IVF）周期给予hCG当日高P水平对着床期子宫内膜表观遗传修饰的影响。设计：回顾性研究。地点：大学辅助生殖单位。患者：共招募了40名患者：20名高P水平的女性与20名正常P水平的女性进行比较。干预措施：在给药当天P水平正常或高的妇女，于给药7天后收集子宫内膜组织。进行DNA甲基化（5-甲基胞嘧啶，5-mC）、组蛋白甲基化（H3K4me2/3, H3K9me2, H3K27me3）和组蛋白乙酰化（H3K4ac, H3K9ac）的免疫组化染色。主要观察指标：分别对管腔上皮、腺上皮和间质进行半定量分析。比较P、雌激素水平和表观遗传标记之间的相关性。结果：在管腔上皮中，高P组H3K9me2表达明显高于正常P组。在腺上皮中，高P组5-mC、H3K9me2、H3K9ac的表达明显高于正常P组。在间质中，高P组H3K27me3的表达明显高于正常P组。5-mC在腺上皮、H3k9me2在腺上皮和管腔上皮、H3K27me3在间质中的表达与P水平显著相关。腺上皮H3k9me2与雌激素水平显著相关。结论：体外受精周期给予hCG当天的高P水平影响着床期子宫内膜三个腔室的表观遗传修饰。表观遗传标记的表达主要与磷水平相关。子宫内膜表观遗传修饰状态的改变可能会破坏高P妇女在给予hCG当天的子宫内膜容受性。(C) 2017年由美国生殖医学学会出版。
Objective: To investigate the effects of high P level on the day of hCG administration in IVF cycles on epigenetic modifications of endometrium in the peri-implantation period.Design: Retrospective study.Setting: University assisted reproductive unit.Patient(s): Forty patients were recruited: 20 women with high P levels were compared with 20 women with normal P levels.Intervention(s): Endometrial tissues were collected 7 days after hCG administration in women with normal or high P levels on the day of hCG administration. Immunohistochemical staining of DNA methylation (5-methylcytosine, 5-mC), histone methylation (H3K4me2/3, H3K9me2, H3K27me3), and histone acetylation (H3K4ac, H3K9ac) was performed.Main Outcome Measure(s): A semiquantitative analysis was performed in the luminal epithelium, glandular epithelium, and stroma, separately. Correlations between P, estrogen levels, and epigenetic markers were compared.Result(s): In luminal epithelium, the expression of H3K9me2 in the high P group was significantly higher than that in the normal P group. In glandular epithelium, the expression of 5-mC, H3K9me2, and H3K9ac in the high P group was significantly higher than that in the normal P group. In stroma, the expression of H3K27me3 in the high P group was significantly higher than that in the normal P group. Expression of 5-mC in glandular epithelium, H3k9me2 in glandular and luminal epithelium, and H3K27me3 in stroma was significantly correlated with P levels. H3k9me2 in glandular epithelium was significantly correlated with estrogen levels.Conclusion(s): High P level on the day of hCG administration in IVF cycles affects epigenetic modifications in three compartments of endometrium in the peri-implantation period. The epigenetic markers' expression was mainly correlated with P level. The altered epigenetic modification status in the endometrium may disrupt the endometrial receptivity in women with high P on the day of hCG administration. (C) 2017 by American Society for Reproductive Medicine.