Yujing Xiong1, Jianzhang Wang1, Liu Liu2, Xiaoyan Chen3, Hui Xu3, Tin Chiu Li3, Chi Chiu Wang4, Songying Zhang5. 1. 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. 2. Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, People's Republic of China. 3. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong. 4. 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; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong. 5. Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, People's Republic of China. Electronic address: zhangsongying@126.com.
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.
RCT Entities:
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.
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