Aging alters mRNA processing in the mouse ovary

Abstract

Aging in females predominantly impacts the ovaries before any other organ systems. This has profound implications for womens reproductive health. This phenomenon is closely linked to a gradual depletion of the ovarian follicle reserve and a notable diminishment of oocyte quality. Studies have shown that cellular changes within ovaries can manifest even before the observable depletion of ovarian follicles. To understand the molecular mechanisms underlying these changes, we have conducted a comprehensive analysis of the changes in gene expression in aging mouse ovaries. Using efficient genomics software such as CLC Genomic Workbench, we could detect not only the differentially expressed genes but also delineate the various transcript variants present in the transcriptome of aging ovaries. We verified the results by comparing coding sequences of selected transcripts with the coding sequences of their canonical counterparts from young and aged mice. In general, the analysis methods yielded similar observations. Our findings revealed that traditional gene expression analyses often overlook the differential expression of numerous transcript variants. We identified significant alterations in the expression patterns of alternative transcripts in aging ovaries and found coding sequences that lead to profound functional outcomes. Notably, most of these differentially expressed transcript variants were affected upstream epigenetically and transcriptionally, then generated through alternative splicing events. This suggests that aging may lead to alterations in RNA-binding proteins and spliceosome components, which play a crucial role in mRNA processing within the mouse ovary. Our observations highlight the necessity of focusing on transcript variants and their functions in aging research, as they provide a more nuanced understanding of the biological processes at play.