Investigating the ovarian alternative splicing landscape during reproductive aging and the impact on ovarian function
Poster #: 126
Session/Time: A
Author:
Adnan Alsamaraee, BS
Mentor:
Pavla Brachova, BS, PhD
Research Type: Basic Science
Abstract
INTRODUCTION:
Female reproductive aging alters ovarian function, leading to a decline in oocyte quantity and quality. However, the underlying molecular mechanisms driving ovarian decline remain poorly understood. At the cellular level aging is associated with widespread changes, including mitochondrial dysfunction, altered metabolism, increased oxidative stress, and disruptions in post-transcriptional regulatory processes. At the molecular level, emerging evidence indicates that alternative splicing undergoes extensive age-related changes, as reflected by aberrant splicing events and altered expression of splicing factors. Age-associated splicing changes modulate protein diversity, producing isoforms that may impair key pathways of metabolism, steroidogenesis, mitochondrial function, and stress response. However, the role of alternative splicing in reproductive aging, particularly its impact on ovarian function, remains largely unexplored. Our preliminary transcriptomic analyses of reproductively aged mouse ovaries identified an increase in splicing factor expression and distinct splicing patterns, including a significant abundance of unannotated transcript isoforms of genes involved in metabolism and other key cellular functions.
METHODS:
To build upon these findings, we are employing global spatial transcriptomics coupled with long-read sequencing to determine cell type specific changes in alternative splicing networks. To do this, gonadotropin stimulated and unstimulated ovaries from young (6 weeks) and reproductively aged (14 months) C57BL/6 mice will be sequenced using 10X Genomics Visium HD 3′ technology and long-read cDNA sequencing using Oxford Nanopore Technologies.
RESULTS:
Based on our preliminary long-read direct RNA-sequencing data, we expect to identify widespread alternative splicing changes in reproductively aged ovaries. Our spatial transcriptomics approach enables comprehensive mapping of splicing alterations at the single cell level.
CONCLUSION:
Integrating isoform remodeling with spatial context, the spatial map will demonstrate how cell type-specific changes in splicing orchestrate organ-wide alterations in ovarian function across aging. Ultimately, our findings will deepen our understanding of ovarian aging and may reveal new approaches for preserving female reproductive health.
Female reproductive aging alters ovarian function, leading to a decline in oocyte quantity and quality. However, the underlying molecular mechanisms driving ovarian decline remain poorly understood. At the cellular level aging is associated with widespread changes, including mitochondrial dysfunction, altered metabolism, increased oxidative stress, and disruptions in post-transcriptional regulatory processes. At the molecular level, emerging evidence indicates that alternative splicing undergoes extensive age-related changes, as reflected by aberrant splicing events and altered expression of splicing factors. Age-associated splicing changes modulate protein diversity, producing isoforms that may impair key pathways of metabolism, steroidogenesis, mitochondrial function, and stress response. However, the role of alternative splicing in reproductive aging, particularly its impact on ovarian function, remains largely unexplored. Our preliminary transcriptomic analyses of reproductively aged mouse ovaries identified an increase in splicing factor expression and distinct splicing patterns, including a significant abundance of unannotated transcript isoforms of genes involved in metabolism and other key cellular functions.
METHODS:
To build upon these findings, we are employing global spatial transcriptomics coupled with long-read sequencing to determine cell type specific changes in alternative splicing networks. To do this, gonadotropin stimulated and unstimulated ovaries from young (6 weeks) and reproductively aged (14 months) C57BL/6 mice will be sequenced using 10X Genomics Visium HD 3′ technology and long-read cDNA sequencing using Oxford Nanopore Technologies.
RESULTS:
Based on our preliminary long-read direct RNA-sequencing data, we expect to identify widespread alternative splicing changes in reproductively aged ovaries. Our spatial transcriptomics approach enables comprehensive mapping of splicing alterations at the single cell level.
CONCLUSION:
Integrating isoform remodeling with spatial context, the spatial map will demonstrate how cell type-specific changes in splicing orchestrate organ-wide alterations in ovarian function across aging. Ultimately, our findings will deepen our understanding of ovarian aging and may reveal new approaches for preserving female reproductive health.