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http://hdl.handle.net/11375/16507
Title: | Characterizing the impact of maternal obesity on offspring ovarian development in rats |
Authors: | Tsoulis, Michael William |
Advisor: | Deborah, Sloboda |
Department: | Biochemistry and Biomedical Sciences |
Abstract: | Maternal obesity predisposes offspring to non-communicable disease and reproductive dysfunction. Previous work has shown that female rat offspring born to mothers fed a high fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. It is currently unknown what mechanisms are driving this reproductive phenotype, however, the ovary is likely involved. The present study shows that offspring born to HF-fed mothers have impaired ovarian function likely stemming from altered ovarian development early in life. Neonates born to HF fed mothers have reduced AMH signaling that appears to result in more primordial follicles assembled. During the prepubertal period, excess primordial follicles are removed from the primordial follicle pool likely due to increased primordial follicle demise or an increase in the number of growing follicles undergoing atresia. This study shows that as adults, offspring born to HF fed mothers also have more atretic follicles, appearing to be due to decreased FSH responsiveness that could be induced by both low expression levels of the oocyte-secreted factor, GDF9, and high expression levels in antral follicles of the granulosa-cell derived factor, AMH. Changes in ovarian follicle dynamics was not associated with increased oxidative stress or the induction of inflammation. Interestingly, the addition of a postweaning high fat diet appears to spare offspring born to HF fed mothers from an increase in follicular atresia. This study demonstrates that maternal HF diet induced obesity has long lasting effects on ovarian development and function in female offspring. Given the high rates of obesity in female populations worldwide and the growing concern over trans-generational inheritance of disease risk, future studies are needed to fully delineate the molecular mechanisms mediating ovarian dysfunction induced by a maternal obesogenic diet. This will allow the design of targeted interventions that will hopefully improve the health of future generations. |
URI: | http://hdl.handle.net/11375/16507 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Masters_Thesis_MT_with_Bib.pdf | 3.5 MB | Adobe PDF | View/Open |
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