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

Author:

Zhou Zixue1,Yang Xi12,Pan Yuncheng1,Shang Lingyue1,Chen Siyuan1,Yang Jialin1,Jin Li1,Zhang Feng123ORCID,Wu Yanhua134ORCID

Affiliation:

1. Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), State Key Laboratory of Genetic Engineering at School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200011, China

2. Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, China

3. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China

4. National Demonstration Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai 200433, China

Abstract

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.

Funder

Ministry of Science and Technology

Shanghai Municipal Science and Technology Commission

National Natural Science Foundation of China

Natural Science Foundation of Shanghai

National Key Research and Development Program of China

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology,General Medicine

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