More couples worldwide, delay their childbearing years. The increase in age causes a gradual decrease in female ovarian function and fertility, leading to an exponential decrease in women over 35 years of age having children. Although promising for some, assisted reproductive technology (ART) is not promising for older women. Decreased fertility in advanced age has become a growing concern in the field of reproduction. In this study, high-throughput transcriptome sequencing was used to identify the differentially expressed genes (DEGs) in the ovarian granulosa cells (GCs) of older women (aged 35-44) with infertility and younger women (aged 25-34). The enriched functions and signaling pathways of DEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The function of DEGs were analyzed and predicted combined with clinical ART data. Sequencing results were verified by quantitative reverse transcription-polymerase chain reaction. Retrospective clinical data and bioinformatics analyses revealed marked reductions in the retrieved oocyte, metaphase II oocyte, 2PN fertilization, and effective embryo numbers in older women. Although the clinical pregnancy and live birth rates did not differ notably between the groups, the miscarriage rate increased significantly in older women. In total, 620 DEGs were identified, of which 246 were upregulated, and 374 were downregulated in the older group. GO, and KEGG analyses indicated that the mechanism of fertility decline in older women was probably related to chronic inflammation, cytokine receptor interaction, and oxidative stress. In conclusion, combined with basic clinical ART data and pregnancy outcomes, we tried to provide a more intuitive and in-depth understanding of age-related reduction in ovarian function and pathogenesis of infertility with regard to chronic inflammation and oxidative stress.
Keywords: Age-related fertility decline; RNA-sequencing; differentially expressed genes; ovarian granulosa cells.