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人绒毛膜促性腺激素注射日子宫内膜孕激素水平对种植窗期子宫内膜表观遗传学修饰的影响。

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.

机构信息

Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong; Reproduction and Development, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.

Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, People's Republic of China.

出版信息

Fertil Steril. 2017 Aug;108(2):269-276.e1. doi: 10.1016/j.fertnstert.2017.06.004.

DOI:10.1016/j.fertnstert.2017.06.004
PMID:28778281
Abstract

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.

摘要

目的

研究在体外受精(IVF)周期中 hCG 给药日高 P 水平对种植窗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

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 hCG 给药日 P 水平正常或高的女性中,在 hCG 给药后 7 天收集子宫内膜组织。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)的免疫组织化学染色。

主要观察指标

分别在腔上皮、腺上皮和基质中进行半定量分析。比较 P、雌激素水平与表观遗传标志物之间的相关性。

结果

在腔上皮中,高 P 组的 H3K9me2 表达明显高于正常 P 组。在腺上皮中,高 P 组的 5-mC、H3K9me2 和 H3K9ac 表达明显高于正常 P 组。在基质中,高 P 组的 H3K27me3 表达明显高于正常 P 组。腺上皮中的 5-mC、腺上皮和腔上皮中的 H3k9me2 以及基质中的 H3K27me3 的表达与 P 水平显著相关。腺上皮中的 H3k9me2 与雌激素水平显著相关。

结论

在 IVF 周期中 hCG 给药日高 P 水平影响种植窗期子宫内膜三个区室的表观遗传修饰。表观遗传标志物的表达主要与 P 水平相关。高 P 水平妇女种植窗期子宫内膜的表观遗传修饰状态改变可能破坏子宫内膜容受性。

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