Mechanisms of chromosome segregation in mammalian oocytes

by Debojit Saha
Doctoral thesis
Date of Examination:2023-12-18
Date of issue:2024-12-10
Advisor:Prof. Dr. Melina Schuh
Referee:Prof. Dr. Markus Bohnsack
Referee:Dr. Ufuk Günesdogan
Referee:Dr. Peter Lenart
Referee:Dr. Alex Faesen
Referee:Dr. Marieke Oudelaar
Persistent Address: http://dx.doi.org/10.53846/goediss-10910

 

 

Files in this item

Name:PhD dissertation_Debojit Saha.pdf
Size:64.9Mb
Format:PDF
Name:Revisionsschein.pdf
Size:58.3Kb
Format:PDF

This file will be freely accessible after 2025-12-17.

Abstract

English

Errors in chromosome segregation in human females often result in eggs with the wrong number of chromosomes, a condition known as aneuploidy. The rate of aneuploidy increases dramatically in women with age, particularly from the mid-30s. Cohesins that hold sister chromatids together are lost from aged oocytes, which results in premature separation of sister chromatids, a leading cause of aneuploidy. However, the mechanism underlying the age-related loss of sister chromatid cohesion remains unclear. In this study, we used high-resolution imaging of mammalian oocytes to identify factors that play a major role in chromosome segregation during meiotic divisions. We also used microscopy, genetics, and proteomics to systematically investigate how changes in these factors with age are associated with increased oocyte aneuploidy. Taken together, the data presented in this thesis provide new insights into the poorly understood process of age-related infertility in women, which may help in the development of therapeutic strategies to reduce aneuploidy-causing errors in mammalian oocytes.
Keywords: Aneuploidy; Age-related infertility; Cohesin; Chromosome segregation errors