Multi-Omics Reveals the Role of Osteopontin/Secreted Phosphoprotein 1 in Regulating Ovarian Aging

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN), is located on chromosome 4q22.1. This multifunctional secreted acidic glycoprotein is expressed intracellularly and extracellularly in various tissues, where it interacts with regulatory proteins and pro-inflammatory immune chemokines, contributing to the pathogenesis of multiple diseases. Nevertheless, the intricate genetic connections between SPP1 and ovarian aging remain largely unexplored. This study aims to bridge this knowledge gap by delving into ovarian aging and its associations with SPP1 using multi-omics data analysis. Our findings indicate that SPP1 is a potential gene related to ovarian aging. To comprehend the role of SPP1, we conducted spatial transcriptomic analyses on young and aged female mouse ovaries, revealing a significant decline in SPP1 expression in the aging group compared to the young group. Similarly, a significantly low level of SPP1 was found in the 73-year-old sample. Additionally, in-depth single-cell RNA-sequencing analysis identified associations between SPP1 and ITGAV, ITGB1, CD44, MMP3, and FN1. Notably, co-expression analysis highlighted a strong correlation between SPP1 and ITGB1. In summary, this study pioneers the identification of SPP1 as a gene implicated in ovarian aging. Further research into the role of SPP1 has the potential to advance precision medicine and improve treatment strategies for ovarian aging-related conditions.