Author ORCID Identifier
https://orcid.org/0000-0001-9025-8045
Date of Award
6-2025
Document Type
Thesis (Ph.D.)
Department or Program
Biological Sciences
First Advisor
Sharon E. Bickel
Second Advisor
Amanda A. Amodeo
Third Advisor
Christopher J. Shoemaker
Abstract
The frequency of trisomic pregnancies exponentially increases with advanced maternal age, a phenomenon known as the maternal age effect. The majority of these aneuploid pregnancies arise from meiotic segregation errors in the oocyte and premature loss of sister chromatid cohesion is a contributing factor. However, the mechanisms that lead to premature cohesion loss during oocyte aging are not fully understood.
Using Drosophila melanogaster as a model organism, work described in this dissertation demonstrates that basal levels of autophagy, a degradation process for damaged organelles and protein aggregates, are required during meiotic prophase for arm cohesion maintenance and accurate meiotic segregation in Drosophila oocytes. Interestingly, immunofluorescence analysis indicates that basal autophagy significantly declines when Drosophila oocytes undergo aging, supporting the hypothesis that a decline in autophagy contributes to age-dependent meiotic segregation errors.
Additionally, I provide evidence that prophase-specific knockdown (KD) of Spermidine Synthase (SpdS), an enzyme involved in the synthesis of polyamine spermidine, causes meiotic chromosome segregation errors that are consistent with precocious loss of arm cohesion. Spermidine is known to stimulate autophagy across species and consistently, SpdS KD disrupts basal autophagy in Drosophila oocytes. This result suggests that dietary supplementation of spermidine may stimulate autophagy and suppress age-dependent segregation errors in oocytes. Together, the results presented in this dissertation broaden our understanding of how cellular processes become compromised in aging oocytes and may inform future strategies to improve oocyte quality and the fidelity of meiotic segregation in women of advanced maternal age.
Recommended Citation
Hilpert, Diana C., "Basal autophagy promotes accurate chromosome segregation in Drosophila oocytes and declines during oocyte aging" (2025). Dartmouth College Ph.D Dissertations. 367.
https://digitalcommons.dartmouth.edu/dissertations/367
