AUTHOR=Chen Lili , Ding Bo , Wu Liju , Qiu Jialing , Li Qiong , Ye Zheng , Yang Jinmei 

TITLE=Transcriptome Analysis Reveals the Mechanism of Natural Ovarian Ageing

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.918212

DOI=10.3389/fendo.2022.918212

ISSN=1664-2392

ABSTRACT=Abstract：
Background: The decline in the quantity and quality of oocytes due to ovarian ageing in women is now a significant threat to reproductive health today as the concept of delayed fertility becomes more widespread. However, the molecular mechanisms of natural ovarian ageing have not been fully elucidated.
Method: Here, we used transcriptomic data from 180 normal ovarian tissues from GTEx V8 to analyse the expression profile of ovarian tissues from women with age segments of 20-29 (22 individuals), 30-39 (14 individuals), 40-49 (37 individuals), 50-59 (61 individuals), 60-69 (42 individuals), and 70-79 (4 individuals), respectively. XCELL was used to assess the infiltration score of 64 cell types of ovary. WGCNA was used to characterize the co-expression network during natural aging of the ovary. ClusterprofileR was used for functional enrichment analysis of co-expression modules. MsViper was used for master regulator analysis. 
Results: The infiltration score of endothelial cells and activated antigen-presenting cells during natural ovarian ageing increased significantly at ages 30-39, 40-49 and then decreased, whereas CD4+ Tcm increased with age. WGCNA identified six co-expression modules from ovarian tissue transcriptomic data species, with the red module significantly and positively correlated with senescence and CD4+ Tcm, the turquoise module significantly and positively correlated with Endothelial Cells. We conducted a further in-depth exploration of ovarian tissue for women aged 20-29 and 30-39 years. The GSEA results showed that the Chemoking signaling pathway were significantly activated in the 30-39 year old group, while Oocyte meiosis was significantly inhibited. Finally, the results of msviper found that transcription factors such as KDM1A, PRDM5, ZNF726, PPARG, FOXJ2 and GLI2 were mainly activated in the 20-29 years group, while VAV1, RUNX3, ZC3H12D, MYCL and IRF5 were mainly activated in the 30-39 years group and that these transcription factor activities were diagnostic of ovarian natural ageing (AUC: 0.65-0.71). 
Conclusion: Natural ageing of the ovary is significantly correlated with immune cell infiltration and activation of inflammation-related signalling pathways, with inflammation levels reaching a maximum during early ovarian ageing (30-39, 40-49) and then gradually decreasing thereafter. These studies provide a research basis for exploring the mechanisms of natural ovarian ageing.