Single-cell studies of mammalian ovaries
Doctoral thesis
Date of Examination:2024-02-12
Date of issue:2025-01-31
Advisor:Prof. Dr. Melina Schuh
Referee:Prof. Dr. Melina Schuh
Referee:Prof. Dr. Anne-Christin Hauschild
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Description:Doctoral thesis
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Abstract
English
Ovarian aging progresses more rapidly than in other organs. Female fertility declines exponentially after the age of 35, and as women increasingly delay childbearing, it is paramount to understand the underlying etiology and mechanisms of ovarian aging. In my doctorate, I uncovered several key features of aging by using a combination of transcriptomic and proteomic approaches. At the transcriptomic level, ovarian aging is characterized by changes leading to oxidative stress, decreased progesterone secretion, and increased AP-1 signaling. In addition, I provide evidence that multiparity can slow down advanced maternal aging by reducing these age-related biological processes. Large-scale proteomic profiling revealed that ovaries have a 10-fold higher fraction of extremely long-lived proteins, and that with age, extensive proteome remodeling leads to the decrease in the long-lived proteins of the proteostasis network. Taken together, this body of work provides an important foundation for the large-scale, high-throughput understanding of ovarian aging at the transcriptomic and proteomic levels.
Keywords: ovarian aging; bioinformatics; scRNAseq; oocyte; ovary