Temporal transcriptomic landscape of postnatal mouse ovaries reveals dynamic gene signatures associated with ovarian aging

Abstract The ovary is the most important organ for maintaining female reproductive health, but it fails before most other organs. Aging-associated alterations in gene expression patterns in mammalian ovaries remain largely unknown. In this study, the transcriptomic landscape of postnatal mouse ovari...

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Bibliographic Details
Published in:Human molecular genetics 2021-10, Vol.30 (21), p.1941-1954
Main Authors: Zhou, Zixue, Yang, Xi, Pan, Yuncheng, Shang, Lingyue, Chen, Siyuan, Yang, Jialin, Jin, Li, Zhang, Feng, Wu, Yanhua
Format: Article
Language:English
Subjects:
Animals
Biomarkers
Cellular Senescence - genetics
Computational Biology - methods
DNA Repair
Female
Gene Expression Profiling
Gene Expression Regulation
Gene Ontology
Mice
Mice, Inbred C57BL
Ovarian Follicle - metabolism
Ovary - metabolism
Reproduction - genetics
RNA-Seq
Transcriptome
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Summary:Abstract The ovary is the most important organ for maintaining female reproductive health, but it fails before most other organs. Aging-associated alterations in gene expression patterns in mammalian ovaries remain largely unknown. In this study, the transcriptomic landscape of postnatal mouse ovaries over the reproductive lifespan was investigated using bulk RNA sequencing in C57BL/6 mice. Gene expression dynamics revealed that the lifespan of postnatal mouse ovaries comprised four sequential stages, during which 2517 genes were identified as differentially enriched. Notably, the DNA repair pathway was found to make a considerable and specific contribution to the process of ovarian aging. Temporal gene expression patterns were dissected to identify differences in gene expression trajectories over the lifespan. In addition to DNA repair, distinct biological functions (including hypoxia response, epigenetic modification, fertilization, mitochondrial function, etc.) were overrepresented in particular clusters. Association studies were further performed to explore the relationships between known genes responsible for ovarian function and differentially expressed genes identified in this work. We found that the causative genes of human premature ovarian insufficiency were specifically enriched in distinct gene clusters. Taken together, our findings reveal a comprehensive transcriptomic landscape of the mouse ovary over the lifespan, providing insights into the molecular mechanisms underlying mammalian ovarian aging and supporting future etiological studies of aging-associated ovarian disorders.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/ddab163