{"title":"Comparison of chromatin accessibility remodeling of granulosa cells in patients with endometrioma or pelvic/tubal infertility.","authors":"Songbang Ou, Xuedan Jiao, Yi Li, Ping Pan, Ruiqi Li, Jia Huang, Xiaoyue Sun, Wenjun Wang, Qingxue Zhang, Chunwei Cao, Lina Wei","doi":"10.1007/s10815-024-03302-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To elucidatethe epigenetic alteration associated with impaired oogenesis in endometrioma using multi-omic approaches.</p><p><strong>Methods: </strong>ATAC-seq was performed on the granulosa cells (GCs) of 6 patients (3 with endometrioma and 3 without). Follicular samples from another 20 patients (10 with endometrioma and 10 without) were collected for mRNA-seq analysis of GCs and extracellular vesicles (EVs) of follicular fluid. qRT-PCR validated candidate genes in GCs from 44 newly enrolled patients (19 with endometrioma and 25 without). mRNA abundance was compared with the Mann-Whitney test. Pearson's correlation analyzed relationships between candidate genes and oocyte parameters.</p><p><strong>Results: </strong>Chromatin accessibility and gene expression profiles of GCs from endometrioma patients differed significantly from the pelvic/tubal infertility group. RNA-seq revealed most differentially expressed genes were downregulated (6216/7325) and enriched in the cellular localization pathway. Multi-omics analyses identified 22 significantly downregulated genes in the GCs of endometrioma patients, including PPIF (P < 0.0001) and VEGFA (P = 0.0148). Both genes were further confirmed by qRT-PCR. PPIF (r = 0.46, p = 0.043) and VEGFA (r = 0.45, p = 0.048) correlated with the total number of retrieved oocytes.</p><p><strong>Conclusions: </strong>GC chromatin remodeling may disrupt GC and EV transcriptomes, interfering with somatic cell-oocyte communication and leading to compromised oogenesis in endometrioma patients.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Assisted Reproduction and Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10815-024-03302-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: To elucidatethe epigenetic alteration associated with impaired oogenesis in endometrioma using multi-omic approaches.
Methods: ATAC-seq was performed on the granulosa cells (GCs) of 6 patients (3 with endometrioma and 3 without). Follicular samples from another 20 patients (10 with endometrioma and 10 without) were collected for mRNA-seq analysis of GCs and extracellular vesicles (EVs) of follicular fluid. qRT-PCR validated candidate genes in GCs from 44 newly enrolled patients (19 with endometrioma and 25 without). mRNA abundance was compared with the Mann-Whitney test. Pearson's correlation analyzed relationships between candidate genes and oocyte parameters.
Results: Chromatin accessibility and gene expression profiles of GCs from endometrioma patients differed significantly from the pelvic/tubal infertility group. RNA-seq revealed most differentially expressed genes were downregulated (6216/7325) and enriched in the cellular localization pathway. Multi-omics analyses identified 22 significantly downregulated genes in the GCs of endometrioma patients, including PPIF (P < 0.0001) and VEGFA (P = 0.0148). Both genes were further confirmed by qRT-PCR. PPIF (r = 0.46, p = 0.043) and VEGFA (r = 0.45, p = 0.048) correlated with the total number of retrieved oocytes.
Conclusions: GC chromatin remodeling may disrupt GC and EV transcriptomes, interfering with somatic cell-oocyte communication and leading to compromised oogenesis in endometrioma patients.
期刊介绍:
The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species.
The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.