Proteomic analysis reveals insufficient folliculogenesis in Aging Female associates with infertility

ABSTRACT: The escalating issue of infertility has become a global concern. Female infertility is primarily attributed to the decrease in both the quantity and quality of oocytes with advancing age, which is a significant factor in female infertility. The present study aims to explore the proteomic profile of exosomes obtained from human follicular fluid to identify the protein signature associated with aging and unsuccessful in vitro fertilization (IVF) outcomes. Despite the lack of significant differences in the morphology and particle size of follicular fluid exosomes between the two groups, the proteomic analysis demonstrated a distinct pattern of differentially expressed proteins. B cell activation, pathogen invasion, and disrupted metabolic processes were found to be significantly higher in the aging group, indicating the involvement of these pathways in aging-associated infertility. Moreover, the PI3K-AKT signaling pathway, which is linked to follicle maturation, was identified as the most influential signaling pathway in the aging group. In vivo experiments corroborated the weakened role of exosomes derived from the aging group in follicle maturation. Finally, the study employed a random forest machine learning algorithm, which further suggested that hydrolase activity might play a crucial role in determining the final IVF outcome. The expression of key differentially expressed proteins was validated. This study provides novel insights into the aging-associated protein signature of follicular fluid exosomes and their potential role in infertility. The findings imply that the aging-related protein signature in exosomes could serve to improve the diagnosis and treatment of infertility.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oocyte

SUBMITTER: Zhen Liu  

LAB HEAD: Yang Sheng

PROVIDER: PXD041139 | Pride | 2025-05-06

REPOSITORIES: pride