Epigenetic alterations of CYP19A1 gene in Cumulus cells and its relevance to infertility in endometriosis
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The purpose of the present study was to investigate the epigenetic mechanisms responsible for the aberrant aromatase expression (CYP19A1) in Cumulus Cells (CCs) of infertile endometriosis patients.
Cumulus cells were obtained from 24 infertile patients with and without endometriosis who underwent ovarian stimulation for intracytoplasmic sperm injection. Expression of CYP19A1 gene was quantified using Reverse Transcription Q-PCR. DNA methylation, histone modifications, and binding of Estrogen Receptor, ERβ to regulatory DNA sequences of CYP19A1 gene were evaluated by Chromatin ImmunoPrecipitation (ChIP) assay.
CYP19A1 gene expression in CCs of endometriosis patients was significantly lower than the control group (P = 0.04). Higher incorporation of MeCP2 (as a marker of DNA methylation) on PII and PI.4 promoters, and hypoacetylation at H3K9 in PII and hypermethylation at H3K9 in PI.4 were observed in CYP19A1 gene in endometriosis patients (P < 0.05). Moreover, a decreased level of ERβ binding to PII and an increased level of its binding to PI.3 and PI.4 promoters of CYP19A1 were observed in endometriosis patients when compared to control.
Significant reduction of CYP19A1 gene expression in CCs of endometriosis patients may be the result of epigenetic alterations in its regulatory regions, either by DNA methylation or histone modifications. These epigenetic changes along with differential binding of ERβ (as a transcription factor) in CYP19A1 promoters may impair follicular steroidogenesis, leading to poor Oocyte and embryo condition in endometriosis patients.
KeywordsEndometriosis Epigenetic CYP19A1 Cumulus cell Estrogen receptor beta
The authors thank all the patients that consented to participate in this study and the embryologists at Royan institute, Tehran, Iran., especially Dr. Bahar Movaghar and Dr. Poopak Eftekhari Yazdi, for their help with patient recruitment and associated embryology. Further, the authors would like to acknowledge Mrs. Raha Favaedi, Miss Samaneh Aghajanpour, and Mrs. Neda Soltani for their skilful technical assistance.
Compliance with ethical standards
This cross-sectional study was approved by the Ethics Committees of Iran University of Medical Sciences (IUMS, no: 23108-April 2014) and the Royan Institute. Also, written informed consent was obtained from all case and control subjects prior to the oocyte retrieval.
Conflict of interest
There is no conflict of interest in this study.
This research was supported by the Vice Chancellor of Research at Iran University of Medical Sciences and Royan institute, Tehran, Iran.
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