Strategies for decreasing aneuploidy in mammalian oocytes

by Halima Yusuf
Cumulative thesis
Date of Examination:2024-02-21
Date of issue:2025-01-10
Advisor:Prof. Dr. Melina Schuh
Referee:Prof. Dr. Matthias Dobbelstein
Referee:Prof. Dr. Melina Schuh
Persistent Address: http://dx.doi.org/10.53846/goediss-11002

 

 

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Abstract

English

Female mammals experience a decline in fertility with age that has been attributed to the progressive depletion of the finite ovarian reserve and an increase in the incidence of aneuploid oocytes. Aneuploid oocytes can give rise to aneuploid embryos that are often non-viable, resulting in pregnancy loss. As such, many women over the age of 35 will struggle to conceive. Aneuploidy in oocytes arises from chromosome segregation errors during meiosis. Studies in mice show that the cohesin complex, which stabilizes bivalents and chromosomes, is gradually lost from chromosomes with age, causing changes in bivalent and chromosome structure that prime for missegregation events. Repurposing this knowledge towards clinical application has remained purely aspirational, however. In this context, my thesis focused on developing molecular tools and strategies for reducing aneuploidy in mouse and human oocytes. The data presented within this thesis represent progress towards therapies that target age-related infertility in humans.
Keywords: cohesin; Aneuploidy; oocyte; maternal age effect; infertility