O-105 Chromatin accessibility of oocytes contributes to PCOS transgenerational inheritance

Abstract Study question What is the underlying mechanism contributing to transgenerational defects of oocytes and embryos polycystic ovary syndrome (PCOS)? Summary answer The inheritance abnormal chromatin accessibility in PCOS responsible for defect transgeneration. known already Studies have provided evidence compromised oocyte quality related adverse impacts. Observed animal-model include meiotic abnormalities, mitochondrial dysfunction, increased oxidative stress. Elevated androgen levels are associated with reduced fertilization rates lower cleavage during vitro (IVF) treatment. could be transgenerationally transmitted, unique altered gene expression has been observed metaphase II (MII) from all offspring mice. design, size, duration We profiled transcriptome preimplantation F0-F2 mice, explored whether was abnormalities offspring. Besides, 13 healthy women 8 PCOS, 24 blood samples with/without were analyzed validate molecular mechanisms inheritance. Duration: 2019.5∼2022.12. Participants/materials, setting, methods mice models established by means DHEA-exposure. Smart-seq2 DNase-seq utilized investigate Bioinformatic analysis applied explore differential comparing controls. Common signatures tissues daughters compared control samples. Main results role chance In we transcriptional alteration 2-cell normal There 4229 1197 differentially expressed genes (DEGs) embryos. DEGs includes both maternal factors zygotic genome activation (ZGA) genes. Interestingly, embryos, hundreds pre-activated which silence embryo but Notably, many also F2 supporting oocytes. Mechanismly, changes particular, promoters elevated that Furthermore, signals detected F0 Finally, our data showed some human identified may used as potential predictors phenotype. Limitations, reasons caution Which contribute still unknown. Wider implications findings candidate phenotype provide clues . Trial registration number not applicable