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

To elucidatethe epigenetic alteration associated with impaired oogenesis in endometrioma using multi-omic approaches.

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.

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.

GC chromatin remodeling may disrupt GC and EV transcriptomes, interfering with somatic cell-oocyte communication and leading to compromised oogenesis in endometrioma patients.