Aging Alters mRNA Processing in the Mouse Ovary

Aging in females affects the ovaries before any other organ. This has a significant impact on women's health. Aging results in the gradual depletion of ovarian follicles and a decline in oocyte quality. Studies have shown that cellular changes within ovaries manifest before the depletion of ovarian follicles. To understand the molecular mechanisms underlying these changes, we conducted a comprehensive analysis of gene expression changes in aging mouse ovaries. When RNA sequencing data from 6-month-old mice were compared to those from 12-month-old mice, we identified numerous differentially expressed genes, as well as transcript variants. Transcript variants arise from alternative transcription start sites (TSSs) and alternative pre-mRNA processing. Therefore, we further analyzed a specific set of regulators for these cellular processes. Our findings indicate that ovarian aging alters the expression of epigenetic regulators (ERs) and transcription factors (TFs) that are involved in alternative TSS usage. Ovarian aging also affects the expression of RNA-binding proteins (RBPs) and spliceosome components (SPs), which are essential for pre-mRNA processing. We noticed that variations in transcript variants were more pronounced than those found through gene expression analysis. While 8% of the known TFs and ERs were differentially expressed at the gene level, this increased to 30% at the transcript variant level. Similarly, 3% of the known RBPs but no known SPs were differentially expressed at the gene level, while this increased to 30% at the transcript variant level. These observations highlight the importance of focusing on transcript variants and their functions in aging research, as they may provide insight into the underlying biological processes involved.