子宫内膜异位症或盆腔/输卵管性不孕患者颗粒细胞染色质可及性重塑的比较

Comparison of chromatin accessibility remodeling of granulosa cells in patients with endometrioma or pelvic/tubal infertility.

作者信息

Ou Songbang, Jiao Xuedan, Li Yi, Pan Ping, Li Ruiqi, Huang Jia, Sun Xiaoyue, Wang Wenjun, Zhang Qingxue, Cao Chunwei, Wei Lina

机构信息

Reproductive Medicine Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang Xi Ave, Guangzhou, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

J Assist Reprod Genet. 2025 Feb;42(2):599-609. doi: 10.1007/s10815-024-03302-7. Epub 2024 Nov 1.

DOI:10.1007/s10815-024-03302-7

PMID:39485574

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11871191/

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.

摘要

目的

采用多组学方法阐明与子宫内膜异位症中卵子发生受损相关的表观遗传改变。

方法

对6例患者（3例患有子宫内膜异位症，3例未患）的颗粒细胞进行ATAC测序。收集另外20例患者（10例患有子宫内膜异位症，10例未患）的卵泡样本，用于卵泡液颗粒细胞和细胞外囊泡的mRNA测序分析。qRT-PCR验证了44例新入组患者（19例患有子宫内膜异位症，25例未患）颗粒细胞中的候选基因。采用Mann-Whitney检验比较mRNA丰度。Pearson相关性分析候选基因与卵母细胞参数之间的关系。

结果

子宫内膜异位症患者颗粒细胞的染色质可及性和基因表达谱与盆腔/输卵管性不孕组有显著差异。RNA测序显示，大多数差异表达基因下调（6216/7325），并富集于细胞定位途径。多组学分析确定了子宫内膜异位症患者颗粒细胞中22个显著下调的基因，包括PPIF（P < 0.0001）和VEGFA（P = 0.0148）。这两个基因均通过qRT-PCR进一步得到证实。PPIF（r = 0.46，p = 0.043）和VEGFA（r = 0.45，p = 0.048）与回收的卵母细胞总数相关。